WO2004063355A2 - Novel methods of diagnosis of metastatic cancer, compositions and methods of screening for modulators of matastatic cancer - Google Patents

Novel methods of diagnosis of metastatic cancer, compositions and methods of screening for modulators of matastatic cancer Download PDF

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WO2004063355A2
WO2004063355A2 PCT/US2004/000885 US2004000885W WO2004063355A2 WO 2004063355 A2 WO2004063355 A2 WO 2004063355A2 US 2004000885 W US2004000885 W US 2004000885W WO 2004063355 A2 WO2004063355 A2 WO 2004063355A2
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metastatic
lung cancer
breast cancer
metastatic breast
cancer
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PCT/US2004/000885
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French (fr)
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WO2004063355A3 (en
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Natasha Aziz
Albert Zlotnik
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Protein Design Labs, Inc.
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Publication of WO2004063355A3 publication Critical patent/WO2004063355A3/en

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    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57423Specifically defined cancers of lung
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6876Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes
    • C12Q1/6883Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material
    • C12Q1/6886Nucleic acid products used in the analysis of nucleic acids, e.g. primers or probes for diseases caused by alterations of genetic material for cancer
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/53Immunoassay; Biospecific binding assay; Materials therefor
    • G01N33/574Immunoassay; Biospecific binding assay; Materials therefor for cancer
    • G01N33/57407Specifically defined cancers
    • G01N33/57415Specifically defined cancers of breast
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q1/00Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions
    • C12Q1/68Measuring or testing processes involving enzymes, nucleic acids or microorganisms; Compositions therefor; Processes of preparing such compositions involving nucleic acids
    • C12Q1/6813Hybridisation assays
    • C12Q1/6834Enzymatic or biochemical coupling of nucleic acids to a solid phase
    • C12Q1/6837Enzymatic or biochemical coupling of nucleic acids to a solid phase using probe arrays or probe chips
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/136Screening for pharmacological compounds
    • CCHEMISTRY; METALLURGY
    • C12BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12QMEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEIC ACIDS OR MICROORGANISMS; COMPOSITIONS OR TEST PAPERS THEREFOR; PROCESSES OF PREPARING SUCH COMPOSITIONS; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL OR ENZYMOLOGICAL PROCESSES
    • C12Q2600/00Oligonucleotides characterized by their use
    • C12Q2600/158Expression markers
    • GPHYSICS
    • G01MEASURING; TESTING
    • G01NINVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00Detection or diagnosis of diseases
    • G01N2800/52Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • the invention relates to the identification of nucleic acids and proteins identified by expression profiles, and nucleic acids, products, and antibodies thereto that are involved in metastatic cancer; and to the use of such expression profiles and compositions in diagnosis and therapy of metastatic cancer.
  • the invention further relates to methods for identifying and using agents and/or targets that inhibit metastatic cancer.
  • Metastatic disease can be viewed as two simultaneously occurring diseases; a disease at a primary site, and a related disease at a secondary location distant from the primary site. Each disease may have different mortality rates, for example in cases of metastatic breast or lung cancer to the brain. In such cases untreated brain metastases are rapidly fatal, while primary breast or lung cancer may actually be cureable.
  • cancers metastasize. While there are many variables that determine where metastatic tumors grow, often, the metastatic location is the nearest cluster of small blood vessels found by the circulating cancer cells. Thus, lung cancer commonly metastasizes to the brain; colon cancer commonly metastasizes to the liver. Alternatively, the cancer may have a preferred site of metastasis. For example, the brain is a preferred site for melanoma and small cell lung cancer. A metastasis of a metastasis may develop as well. For example, a colon cancer may metastasize to the liver, which in rum may metastasize to the lung, which may in turn metastasize to the brain.
  • metastasis occurs when cancer cells from the primary site break away and enter the body's circulatory system through the blood stream, lymph system, or spinal fluid and travel to distant locations.
  • cancer metastasis may occur in nearly any organ, brain metastases are one of the most common sites of systemic spread from solid tumors, with an annual incidence of over 100,000 cases. Indeed, metastatic brain tumors occur in about one-fourth of all cancers that metastasize, and primary and metastatic brain tumors kill 15,000 people each year.
  • the most common primary tumors that metastasize to the brain are lung, breast, melanoma, and colon, however almost any cancer has this potential. lthough almost 1 in 4 patients with cancer will develop tumors that spread to the central nervous system (CNS) cancer can metastasize to almost any organ.
  • CNS central nervous system
  • metastatic tumors Classification of metastatic tumors depends on the tissue type from which they are derived. Unfortunately, it is often difficult or impossible to determine the location of the primary cancer and this can unnecessarily complicate diagnosis and treatment of the metastatic cancer. In addition early diagnosis of metastatic cancer can greatly improve the prognostic outlook for a cancer patient. Often metastatic burden, rather than the primary cancer, is what ultimately kills a patient.
  • molecular targets for therapeutic intervention in metastatic breast and lung cancer are provided herein. Additionally, provided herein are methods that can be used in diagnosis and prognosis of metastatic breast and lung cancer. Further provided are methods that can be used to screen candidate bioactive agents for the ability to modulate metastatic cancer including metastatic brain tumors.
  • the present invention therefore provides nucleotide sequences of genes that are up- and down-regulated in metastatic breast or metastatic lung cancer cells. Such genes and the proteins they encode are useful for diagnostic and prognostic purposes, and also as targets for screening for therapeutic compounds that modulate metastatic breast or lung cancer, such as antibodies.
  • the methods of detecting nucleic acids of the invention or their encoded proteins can be used for a number of purposes.
  • Examples include, early detection of breast or lung cancers, monitoring and early detection of relapse following treatment of breast or lung cancers including early detection of metastatic cancer, monitoring response to therapy of breast or lung cancers, determining prognosis of breast or lung cancers, directing therapy of breast or lung cancers, selecting patients for postoperative chemotherapy or radiation therapy, selecting therapy, determining tumor prognosis and the likelihood that a given cancer will metastasize or has metastasized, treatment, or response to treatment, early detection of precancerous conditions and early detection of metastasis.
  • Other aspects of the invention will become apparent to the skilled artisan by the following description of the invention.
  • the present invention provides a method of detecting a metastatic breast or lung cancer-associated transcript in a cell from a patient, the method comprising contacting a biological sample from the patient with a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C.
  • the polynucleotide selectively hybridizes to a sequence at least 95%o identical to a sequence as shown in Tables 1A-12C. In another embodiment, the polynucleotide comprises a sequence as shown in Tables 1 A-12C.
  • the biological sample is a tissue sample.
  • the biological sample comprises isolated nucleic acids, e.g., mRNA.
  • the polynucleotide is labeled, e.g., with a fluorescent label. In one embodiment, the polynucleotide is immobilized on a solid surface.
  • the patient is undergoing a therapeutic regimen to treat metastatic breast or lung cancer.
  • the metastatic breast or lung cancer has metastasized to the brain.
  • the patient is a human.
  • the method further comprises the step of amplifying nucleic acids before the step of contacting the biological sample with the polynucleotide.
  • the present invention provides methods of detecting polypeptide encoded by a metastatic breast or lung cancer-associated transcript in a cell from a patient, the method comprising contacting a biological sample from the patient with an antibody that specifically binds a polypeptide encoded by a sequence at least 80%> identical to a sequence as shown in Tables 1 A-12C.
  • the present invention provides a method of monitoring the efficacy of a therapeutic treatment of metastatic breast or lung cancer, the method comprising the steps of: (i) providing a biological sample from a patient undergoing the therapeutic treatment; and (ii) determining the level of a metastatic breast or lung cancer-associated transcript in the biological sample by contacting the biological sample with a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C, thereby monitoring the efficacy of the therapy.
  • the method further comprises the step of: (iii) comparing the level of the metastatic breast or lung cancer-associated transcript to a level of the metastatic breast or lung cancer-associated transcript in a biological sample from the patient prior to, or earlier in, the therapeutic treatment.
  • the present invention provides a method of monitoring the efficacy of a therapeutic treatment of metastatic breast or lung cancer, the method comprising the steps of: (i) providing a biological sample from a patient undergoing the therapeutic treatment; and (ii) determining the level of a metastatic breast or lung cancer-associated antibody in the biological sample by contacting the biological sample with a polypeptide encoded by a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C, wherein the polypeptide specifically binds to the metastatic breast or lung cancer-associated antibody, thereby monitoring the efficacy of the therapy.
  • the method further comprises the step of: (iii) comparing the level of the metastatic breast or lung cancer-associated antibody to a level of the metastatic breast or lung cancer-associated antibody in a biological sample from the patient prior to, or earlier in, the therapeutic treatment.
  • the present invention provides a method of monitoring the efficacy of a therapeutic treatment of metastatic breast or lung cancer, the method comprising the steps of: (i) providing a biological sample from a patient undergoing the therapeutic treatment; and (ii) determining the level of a metastatic breast or lung cancer-associated polypeptide in the biological sample by contacting the biological sample with an antibody, wherein the antibody specifically binds to a polypeptide encoded by a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1 A- 12C, thereby monitoring the efficacy of the therapy.
  • the method further comprises the step of: (iii) comparing the level of the metastatic breast or lung cancer-associated polypeptide to a level of the metastatic breast or lung cancer-associated polypeptide in a biological sample from the patient prior to, or earlier in, the therapeutic treatment.
  • the present invention provides an isolated nucleic acid molecule consisting of a polynucleotide sequence as shown in Tables 1 A-12C.
  • an expression vector or cell comprises the isolated nucleic acid.
  • the present invention provides an isolated polypeptide which is encoded by a nucleic acid molecule having polynucleotide sequence as shown in Tables 1 A- 12C.
  • the present invention provides an antibody that specifically binds to an isolated polypeptide which is encoded by a nucleic acid molecule having polynucleotide sequence as shown in Tables 1 A-12C.
  • the antibody is conjugated to an effector component, e.g., a fluorescent label, a radioisotope or a cytotoxic chemical.
  • an effector component e.g., a fluorescent label, a radioisotope or a cytotoxic chemical.
  • the antibody is an antibody fragment. In another embodiment, the antibody is humanized.
  • the present invention provides a method of detecting a metastatic breast or lung cancer cell in a biological sample from a patient, the method comprising contacting the biological sample with an antibody as described herein.
  • the present invention provides a method of detecting antibodies specific to metastatic breast or lung cancer in a patient, the method comprising contacting a biological sample from the patient with a polypeptide encoded by a nucleic acid comprises a sequence from Tables 1A-12C.
  • the present invention provides a method for identifying a compound that modulates a metastatic breast or lung cancer-associated polypeptide, the method comprising the steps of: (i) contacting the compound with a metastatic breast or lung cancer-associated polypeptide, the polypeptide encoded by a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C; and (ii) determining the functional effect of the compound upon the polypeptide.
  • the functional effect is a physical effect, an enzymatic effect, or a chemical effect.
  • the polypeptide is expressed in a eukaryotic host cell or cell membrane. In another embodiment, the polypeptide is recombinant.
  • the functional effect is determined by measuring ligand binding to the polypeptide.
  • the present invention provides a method of inhibiting proliferation of a metastatic breast or lung cancer-associated cell to treat breast or lung cancer in a patient, the method comprising the step of administering to the subject a therapeutically effective amount of a compound identified as described herein.
  • the compound is an antibody.
  • the present invention provides a drag screening assay comprising the steps of: (i) administering a test compound to a mammal having metastatic breast or lung cancer or a cell isolated therefrom; (ii) comparing the level of gene expression of a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1 A-12C in a treated cell or mammal with the level of gene expression of the polynucleotide in a control cell or mammal, wherein a test compound that modulates the level of expression of the polynucleotide is a candidate for the treatment of metastatic breast or lung cancer.
  • control is a mammal with metastatic breast or lung cancer or a cell therefrom that has not been treated with the test compound. In another embodiment, the control is a normal cell or mammal.
  • the present invention provides a method for treating a mammal having metastatic breast or lung cancer comprising administering a compound identified by the assay described herein.
  • the present invention provides a pharmaceutical composition for treating a mammal having meta static breast or lung cancer, the composition comprising a compound identified by the assay described herein and a physiologically acceptable excipient.
  • the present invention provides novel methods for diagnosis and treatment of metastatic breast or metastatic lung cancer.
  • the invention is useful for the treatment of metastatic breast and metastatic lung cancer when the cancer is metastasized to the brain, as well as when the cancer is metastasized to other organs and tissues.
  • the invention also provides methods of screening for compositions which modulate metastatic breast cancer or metastatic lung cancer.
  • metastatic tumors are classified by the tissue type from which the cancer cells are derived. Almost any cancer can metastasize. The metastases may occur to any site, however some cancers preferentially metastasize to particular organs. For example lung, breast, head & neck, cervical, and bladder tumors frequently metastasize to particular organs. Specifically, lung cancer metastatisizes to: brain, bone, liver, adrenal glands, lung, pleura, subcutaneous tissue, kidney, lymph nodes, cerebrospinal fluid, pancreas, bone marrow.
  • Brain metastases are a particular concern because of the deadly nature of brain tumors in general. Because the brain is generally unforgiving in its response to both the tumor and therapy, prognosis in cases metastatic brain tumors is especially poor. This is the case whether or not the primary cancer is treatable or even cured.
  • cancer cells metastasize to the brain or other parts of the body depends on many factors including the type of cancer, stage of cancer, and original location of the cancer. Treatment for secondary (metastatic) tumors depends on where the cancer started and the extent of the spread as well as other factors, including the patient's age, general health, and response to previous treatment.
  • metastatic cancer Knowing the origin of metastatic cancer can greatly improve the probable outcome of treatment for individuals with metastatic disease. Indeed, the earlier metastatic cancer can be detected, the better is the prognosis for the individual since it is often metastatic burden that kills a patient. Because metastatic burden increases with time, early detection is essential for successful treatment.
  • Tables 1A-12C provide UniGene cluster identification numbers for the nucleotide sequence of genes that exhibit increased or decreased expression in metastasizing breast and lung cancer samples.
  • Tables 1 A-12C also provide an exemplar accession number that provides a nucleotide sequence that is part of the UniGene cluster.
  • Table 1 A shows about 461 genes upregulated in breast metastases to the brain relative to normal breast tissues.
  • Table 2 A shows about 445 genes upregulated in breast metastases to the brain relative to normal body tissues.
  • Table 3 A shows about 216 genes upregulated in breast metastases to the brain relative to primary breast tumors.
  • Table 4 A shows about 350 genes downregulated in breast metastases to the brain relative to primary breast tumors.
  • Table 5 A shows about 489 genes downregulated in breast metastases to the brain relative to normal breast tissue.
  • Table 6A shows about 1251 genes upregulated in lung metastases to the brain relative to normal lung tissues.
  • Table 7 A shows about 381 genes upregulated in lung metastases to the brain relative to normal body tissues.
  • Table 8A shows about 330 genes upregulated in lung metastases to the brain relative to primary lung tumors.
  • Table 9A shows about 252 genes downregulated in lung metastases to the brain relative to primary lung tumors.
  • Table 10A shows about 289 genes downregulated in lung metastases to the brain relative to normal lung tissue.
  • Table 11 A shows about 1198 genes upregulated in breast and lung metastases to the brain relative to normal body tissues.
  • Table 12A shows about 2867 genes upregulated in breast and lung metastases to the brain relative to normal breast and lung tissues.
  • Tables and analysis herein is derived primarily from metastases to the brain, it is expected that markers identified from these samples should also be expressed in metastasis to other organs, particularly metastasis originating from tumors in the lung, breast, head and neck, cervix, and bladder.
  • the tumor-specific genes expressed in lung tumors are often also expressed in head and neck, cervical, and bladder tumors Therefore, the genes identified in metastases of primary lung tumors may also be expressed in primary tumors and metastases arising from primary tumors of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oral pharynx, lip, larynx, hypopharynx, salivary glands, paragangliomas, esophagus, cervix, vagina, vulva, or bladder.
  • the identified metastatic markers should be useful in diagnosis, prognosis, or therapy of metastases from these cancers.
  • sequences identified in Tables 1 A-12C exhibited increased or decreased expression in metastasizing breast or lung cancer samples
  • the sequences of the invention, and their encoded proteins can also be used to diagnose, treat or prevent cancers in patients with non-metastatic breast cancers or non- metastatic lung cancers. Alteration of gene expression for a gene in Tables 1A-12C may be more likely or less likely to indicate that the subject will progress to metastatic disease. The sequences can also be used to diagnose, treat or prevent precancerous or benign conditions. Alteration of gene expression for a gene in Tables 1A-12C may or may not indicate that the subject is more likely to progress to cancer or to metastatic disease.
  • the specification focuses primarily on metastasizing breast or lung cancer, the methods described below can also be applied to non-metastasizing breast or lung cancers and precancerous or benign conditions as well. Definitions
  • metal breast cancer protein or “metastatic breast cancer polynucleotide” or “metastatic breast cancer-associated transcript” refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a nucleotide sequence of or associated with a UniGene cluster of Tables 1-5, 11, and 12; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence encoded by a nucleotide sequence of or associated with a UniGene cluster
  • a polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal.
  • a "metastatic breast cancer polypeptide” and a “metastatic breast cancer polynucleotide,” include both naturally occurring or recombinant.
  • metal lung cancer protein or “metastatic lung cancer polynucleotide” or “metastatic lung cancer-associated transcript” refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a nucleotide sequence of or associated with a UniGene cluster of Tables 6A-12C; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence encoded by a nucleotide sequence of or associated with a UniGene cluster of Table
  • a polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal.
  • a "metastatic lung cancer polypeptide” and a “metastatic lung cancer polynucleotide,” include both naturally occurring or recombinant.
  • metalastasis refers to the process by which a disease shifts from from one part of the body to another. This process may include the spreading of neoplasms from the site of a primary tumor to distant parts of the body.
  • metalastatic brain tumor refers to a tumor of the brain and/or its associated bone, blood vessels, meninges etc that has developed as a result of the metastasis of cancer from a primary site to the brain.
  • second brain tumor refers to a metastatic brain tumor as defined above.
  • metastatic breast cancer refers to any cancer in any part of the body which has its origins in breast cancer tissue. Metastatic breast cancer includes, but is not limited to "metastatic brain tumors” that have their origin in a primary breast cancer, and pre- metastatic primary tumor cells in the process of developing a metastatic phenotype.
  • Metastatic lung cancer refers to any cancer in any part of the body which has its origins in lung cancer tissue. Metastatic lung cancer includes, but is not limited to "metastatic brain tumors” that have their origin in a primary lung cancer, and pre-metastatic primary tumor cells in the process of developing a metastatic phenotype.
  • a “full length” metastatic breast or lung cancer protein or nucleic acid refers to a metastatic breast or lung cancer polypeptide or polynucleotide sequence, or a variant thereof, that contains all of the elements normally contained in one or more naturally occurring, wild type metastatic breast or lung cancer polynucleotide or polypeptide sequences.
  • the “full length” may be prior to, or after, various stages of post-translation processing or splicing, including alternative splicing.
  • "Biological sample” as used herein is a sample of biological tissue or fluid that contains nucleic acids or polypeptides, e.g., of a metastatic breast or lung cancer protein, polynucleotide or transcript.
  • Such samples include, but are not limited to, tissue isolated from primates, e.g., humans, or rodents, e.g., mice, and rats.
  • Biological samples may also include sections of tissues such as biopsy and autopsy samples, frozen sections taken for histologic purposes, blood, plasma, serum, sputum, stool, tears, mucus, hair, skin, etc.
  • Biological samples also include explants and primary and/or transformed cell cultures derived from patient tissues.
  • a biological sample is typically obtained from a eukaryotic organism, most preferably a mammal such as a primate, e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or other mammal; or a bird; reptile; fish.
  • a mammal such as a primate, e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or other mammal; or a bird; reptile; fish.
  • Providing a biological sample means to obtain a biological sample for use in methods described in this invention. Most often, this will be done by removing a sample of cells from an animal, but can also be accomplished by using previously isolated cells (e.g., isolated by another person, at another time, and/or for another purpose), or by performing the methods of the invention in vivo. Archival tissues, having treatment or outcome history, will be particularly useful.
  • nucleic acids or polypeptide sequences refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60% identity, preferably 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%o, 97%>, 98%>, 99%o, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection.
  • sequences are then said to be "substantially identical.”
  • This definition also refers to, or may be applied to, the compliment of a test sequence.
  • the definition also includes sequences that have deletions and/or additions, as well as those that have substitutions, as well as naturally occurring, e.g., polymorphic or allelic variants, and man-made variants.
  • the preferred algorithms can account for gaps and the like.
  • identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.
  • sequence comparison typically one sequence acts as a reference sequence, to which test sequences are compared.
  • test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated.
  • sequence algorithm program parameters Preferably, default program parameters can be used, or alternative parameters can be designated.
  • sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.
  • a “comparison window”, as used herein, includes reference to a segment of one of the number of contiguous positions selected from the group consisting typically of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned.
  • Methods of alignment of sequences for comparison are well-known in the art.
  • Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol.
  • BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention.
  • Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information.
  • This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive- valued threshold score T when aligned with a word of the same length in a database sequence.
  • T is referred to as the neighborhood word score threshold (Altschul et al, supra).
  • a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative- scoring residue alignments; or the end of either sequence is reached.
  • the BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment.
  • the BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. N t 7. Acad. Sci. USA 90:5873-5787 (1993)).
  • One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P( ⁇ )), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance.
  • P( ⁇ ) the smallest sum probability
  • a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01 , and most preferably less than about 0.001.
  • Log values may be large negative numbers, e.g., 5, 10, 20, 30, 40, 40, 70, 90, 110, 150, 170, etc.
  • nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid, as described below.
  • a polypeptide is typically substantially identical to a second polypeptide, e.g., where the two peptides differ only by conservative substitutions.
  • Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described below.
  • Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequences.
  • a "host cell” is a naturally occurring cell or a transformed cell that contains an expression vector and supports the replication or expression of the expression vector.
  • Host cells may be cultured cells, explants, cells in vivo, and the like.
  • Host cells may be prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect, amphibian, or mammalian cells such as CHO, HeLa, and the like (see, e.g., the American Type Culture Collection catalog or web site, www.atcc.org).
  • isolated refers to material that is substantially or essentially free from components that normally accompany it as found in its native state. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein or nucleic acid that is the predominant species present in a preparation is substantially purified. In particular, an isolated nucleic acid is separated from some open reading frames that naturally flank the gene and encode proteins other than protein encoded by the gene.
  • purified in some embodiments denotes that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel.
  • nucleic acid or protein is at least 85% pure, more preferably at least 95% pure, and most preferably at least 99%> pure.
  • “Purify” or “purification” in other embodiments means removing at least one contaminant from the composition to be purified. In this sense, purification does not require that the purified compound be homogenous, e.g., 100% pure.
  • polypeptide peptide
  • protein protein
  • amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers, those containing modified residues, and non-naturally occurring amino acid polymer.
  • amino acid refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to the naturally occurring amino acids.
  • Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, ⁇ - carboxyglutamate, and O-phosphoserine.
  • Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, e.g., an carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium.
  • Such analogs may have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid.
  • Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions similarly to a naturally occurring amino acid.
  • Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
  • Constantly modified variants applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical or associated, e.g., naturally contiguous, sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode most proteins. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine.
  • nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes silent variations of the nucleic acid.
  • AUG which is ordinarily the only codon for methionine
  • TGG which is ordinarily the only codon for tryptophan
  • nucleic acid which encodes a polypeptide is implicit in a described sequence with respect to the expression product, but not with respect to actual probe sequences.
  • amino acid sequences one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.
  • the following eight groups each contain amino acids that are typically conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)).
  • Macromolecular structures such as polypeptide structures can be described in terms of various levels of organization. For a general discussion of this organization, see, e.g., Alberts et al, Molecular Biology of the Cell (3 rd ed., 1994) and Cantor & Schimmel, Biophysical Chemistiy Part I: The Conformation of Biological Macromolecules (1980).
  • Primary structure refers to the amino acid sequence of a particular peptide.
  • “Secondary structure” refers to locally ordered, three dimensional structures within a polypeptide. These structures are commonly known as domains. Domains are portions of a polypeptide that often form a compact unit of the polypeptide and are typically 25 to approximately 500 amino acids long.
  • Typical domains are made up of sections of lesser organization such as stretches of ⁇ -sheet and ⁇ -helices.
  • Tetiary structure refers to the complete three dimensional structure of a polypeptide monomer.
  • Quaternary structure refers to the three dimensional structure formed, usually by the noncovalent association of independent tertiary units. Anisotropic terms are also known as energy terms.
  • Nucleic acid or “oligonucleotide” or “polynucleotide” or grammatical equivalents used herein means at least two nucleotides covalently linked together. Oligonucleotides are typically from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50 or more nucleotides in length, up to about 100 nucleotides in length. Nucleic acids and polynucleotides are a polymers of any length, including longer lengths, e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000, 10,000, etc.
  • a nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have alternate backbones, comprising, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O- methylphophoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press); and peptide nucleic acid backbones and linkages.
  • Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non- ribose backbones, including those described in U.S. Patent Nos.
  • nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose- phosphate backbone may be done for a variety of reasons, e.g. to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made.
  • PNA peptide nucleic acids
  • These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in two advantages.
  • the PNA backbone exhibits improved hybridization kinetics. PNAs have larger changes in the melting temperature (T m ) for mismatched versus perfectly matched basepairs. DNA and RNA typically exhibit a 2-4°C drop in T m for an internal mismatch. With the non-ionic PNA backbone, the drop is closer to 7-9°C.
  • T m melting temperature
  • hybridization of the bases attached to these backbones is relatively insensitive to salt concentration.
  • PNAs are not degraded by cellular enzymes, and thus can be more stable.
  • the nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence.
  • the depiction of a single strand also defines the sequence of the complementary strand; thus the sequences described herein also provide the complement of the sequence.
  • the nucleic acid may be DNA, both genomic and cDNA, RNA or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc.
  • Transcript typically refers to a naturally occurring RNA, e.g., a pre-mRNA, linRNA, or mRNA.
  • nucleoside includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides.
  • nucleoside includes non-naturally occurring analog structures. Thus, e.g. the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside.
  • a “label” or a “detectable moiety” is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means.
  • useful labels include 32 P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins or other entities which can be made detectable, e.g., by incorporating a radiolabel into the peptide or used to detect antibodies specifically reactive with the peptide.
  • effector or “effector moiety” or “effector component” is a molecule that is bound (or linked, or conjugated), either covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds, to an antibody.
  • the "effector” can be a variety of molecules including, e.g., detection moieties including radioactive compounds, fluorescent compounds, an enzyme or substrate, tags such as epitope tags, a toxin; activatable moieties, a chemotherapeutic agent; a lipase; an antibiotic; or a radioisotope emitting "hard” e.g., beta radiation.
  • a "labeled nucleic acid probe or oligonucleotide” is one that is bound, either covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds to a label such that the presence of the probe may be detected by detecting the presence of the label bound to the probe.
  • method using high affinity interactions may achieve the same results where one of a pair of binding partners binds to the other, e.g., biotin, streptavidin.
  • nucleic acid probe or oligonucleotide is defined as a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation.
  • a probe may include natural (i.e., A, G, C, or T) or modified bases (7-deazaguanosine, inosine, etc.).
  • the bases in a probe may be joined by a linkage other than a phosphodiester bond, so long as it does not functionally interfere with hybridization.
  • probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages. It will be understood by one of skill in the art that probes may bind target sequences lacking complete complementarity with the probe sequence depending upon the stringency of the hybridization conditions.
  • the probes are preferably directly labeled as with isotopes, chromophores, lumiphores, chromogens, or indirectly labeled such as with biotin to which a streptavidin complex may later bind. By assaying for the presence or absence of the probe, one can detect the presence or absence of the select sequence or subsequence. Diagnosis or prognosis may be based at the genomic level, or at the level of RNA or protein expression.
  • recombinant when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified.
  • recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all.
  • nucleic acid By the term “recombinant nucleic acid” herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid, e.g., using pofymerases and endonucleases, in a form not normally found in nature. In this manner, operably linkage of different sequences is achieved.
  • an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined are both considered recombinant for the purposes of this invention.
  • a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, i.e., using the hi vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non-recombinantly, are still considered recombinant for the purposes of the invention.
  • a "recombinant protein” is a protein made using recombinant techniques, i.e., through the expression of a recombinant nucleic acid as depicted above.
  • heterologous when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not normally found in the same relationship to each other in nature.
  • the nucleic acid is typically recombinantly produced, having two or more sequences, e.g., from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source.
  • a heterologous protein will often refer to two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
  • a “promoter” is defined as an array of nucleic acid control sequences that direct transcription of a nucleic acid.
  • a promoter mcludes necessary nucleic acid sequences near the start site of transcription, such as, in the case of a polymerase II type promoter, a TATA element.
  • a promoter also optionally includes distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription.
  • a “constitutive” promoter is a promoter that is active under most environmental and developmental conditions.
  • An “inducible” promoter is a promoter that is active under environmental or developmental regulation.
  • operably linked refers to a functional linkage between a nucleic acid expression control sequence (such as a promoter, or array of transcription factor binding sites) and a second nucleic acid sequence, wherein the expression control sequence directs transcription of the nucleic acid corresponding to the second sequence.
  • a nucleic acid expression control sequence such as a promoter, or array of transcription factor binding sites
  • an "expression vector” is a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid in a host cell.
  • the expression vector can be part of a plasmid, virus, or nucleic acid fragment.
  • the expression vector includes a nucleic acid to be transcribed operably linked to a promoter.
  • the phrase “selectively (or specifically) hybridizes to” refers to the binding, duplexing, or hybridizing of a molecule only to a particular nucleotide sequence under stringent hybridization conditions when that sequence is present in a complex mixture (e.g., total cellular or library DNA or RNA).
  • stringent hybridization conditions refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acids, but to essentially no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology— Hybridization with Nucleic Probes, "Overview of principles of hybridization and the strategy of nucleic acid assays” (1993). Generally, stringent conditions are selected to be about 5-10°C lower than the thermal melting point (T m ) for the specific sequence at a defined ionic strength pH.
  • T m thermal melting point
  • the T m is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at T m , 50% of the probes are occupied at equilibrium).
  • Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°C for short probes (e.g., 10 to 50 nucleotides) and at least about 60°C for long probes (e.g., greater than 50 nucleotides).
  • Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide.
  • a positive signal is at least two times background, preferably 10 times background hybridization.
  • Exemplary stringent hybridization conditions are often: 50% formamide, 5x SSC, and 1% SDS, incubating at 42°C, or, 5x SSC, 1% SDS, incubating at 65°C, with wash in 0.2x SSC, and 0.1% SDS at 65°C.
  • a temperature of about 36°C is typical for low stringency amplification, although annealing temperatures may vary between about 32°C and 48°C depending on primer length.
  • a temperature of about 62°C is typical, although high stringency annealing temperatures can range from about 50°C to about 65°C, depending on the primer length and specificity.
  • Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90°C - 95°C for 30 sec - 2 min., an annealing phase lasting 30 sec. - 2 min., and an extension phase of about 72°C for 1 - 2 min. Protocols and guidelines for low and high stringency amplification reactions are provided, e.g., in Innis et al, PCR Protocols, A Guide to Methods and Applications (1990).
  • Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions.
  • Exemplary "moderately stringent hybridization conditions” include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37°C, and a wash in IX SSC at 45°C. A positive hybridization is at least twice background.
  • Those of ordinary skill will readily recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous reference, e.g., see, e.g., Current Protocols in Molecular Biology (Ausubel et al, eds. 1995 supplement).
  • metastatic breast cancer or metastatic lung cancer protein includes the determination of a parameter that is indirectly or directly under the influence of the metastatic breast cancer or metastatic lung cancer protein or nucleic acid, e.g., an enzymatic, functional, physical, or chemical effect, such as the ability to decrease metastatic breast cancer or metastatic lung cancer.
  • ligand binding activity includes cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis, and other characteristics of metastatic breast cancer or metastatic lung cancer cells.
  • “Functional effects” include in vitro, in vivo, and ex vivo activities.
  • determining the functional effect is meant assaying for a compound that increases or decreases a parameter that is indirectly or directly under the influence of a metastatic breast cancer or metastatic lung cancer protein sequence, e.g., functional, enzymatic, physical and chemical effects.
  • Such functional effects can be measured by any means known to those skilled in the art, e.g., changes in spectroscopic characteristics (e.g., fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape), chromatographic, or solubility properties for the protein, measuring inducible markers or transcriptional activation of the metastatic breast cancer or metastatic lung cancer protein; measuring binding activity or binding assays, e.g., binding to antibodies or other ligands, and measuring cellular proliferation.
  • spectroscopic characteristics e.g., fluorescence, absorbance, refractive index
  • hydrodynamic e.g., shape
  • chromatographic, or solubility properties for the protein, measuring inducible markers or transcriptional activation of the metastatic
  • Determination of the functional effect of a compound on metastatic breast cancer or metastatic lung cancer can also be performed using metastatic breast cancer or • metastatic lung cancer assays known to those of skill in the art such as an in vitro assays, e.g., cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis, and other characteristics of metastatic breast cancer or metastatic lung cancer cells.
  • an in vitro assays e.g., cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis, and other characteristics of metastatic breast cancer or metastatic lung cancer
  • the functional effects can be evaluated by many means known to those skilled in the art, e.g., microscopy for quantitative or qualitative measures of alterations in morphological features, measurement of changes in RNA or protein levels for metastatic breast cancer or metastatic lung cancer-associated sequences, measurement of RNA stability, identification of downstream or reporter gene expression (CAT, luciferase, /3-gal, GFP and the like), e.g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, inducible markers, and ligand binding assays.
  • CAT reporter gene expression
  • Inhibitors are used to refer to activating, inhibitory, or modulating molecules or compounds identified using in vitro and in vivo assays of metastatic breast cancer or metastatic lung cancer polynucleotide and polypeptide sequences of the invention.
  • Inhibitors are compounds that, e.g., bind to, partially or totally block activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity or expression of metastatic breast cancer or metastatic lung cancer proteins of the invention, e.g., antagonists.
  • Antisense nucleic acids may seem to inhibit expression and subsequent function of the protein.
  • Activators are compounds that increase, open, activate, facilitate, enhance activation, sensitize, agonize, or up regulate metastatic breast cancer or metastatic lung cancer protein activity.
  • Inhibitors, activators, or modulators also include genetically modified versions of metastatic breast cancer or metastatic lung cancer proteins, e.g., versions with altered activity, as well as naturally occurring and synthetic ligands, antagonists, agonists, antibodies, small chemical molecules and the like.
  • Such assays for inhibitors and activators include, e.g., expressing the metastatic breast cancer or metastatic lung cancer protein in vitro, in cells, or cell membranes, applying putative modulator compounds, and then determining the functional effects on activity, as described above.
  • Activators and inhibitors of metastatic breast cancer or metastatic lung cancer can also be identified by incubating metastatic breast cancer or metastatic lung cancer cells with the test compound and determining increases or decreases in the expression of 1 or more metastatic breast cancer or metastatic lung cancer proteins, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50 or more metastatic breast cancer or metastatic lung cancer proteins, such as metastatic breast cancer or metastatic lung cancer proteins encoded by the sequences set out in Tables 1-12.
  • 1 or more metastatic breast cancer or metastatic lung cancer proteins e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50 or more metastatic breast cancer or metastatic lung cancer proteins, such as metastatic breast cancer or metastatic lung cancer proteins encoded by the sequences set out in Tables 1-12.
  • Samples or assays comprising metastatic breast cancer or metastatic lung cancer proteins that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of inhibition.
  • Control samples (untreated with inhibitors) are assigned a relative protein activity value of 100%. Inhibition of a polypeptide is achieved when the activity value relative to the control is about 80%, preferably 50%), more preferably 25-0%).
  • Activation of a metastatic breast cancer or metastatic lung cancer polypeptide is achieved when the activity value relative to the control (untreated with activators) is 110%, more preferably 150%), more preferably 200-500% (i.e., two to five fold higher relative to the control), more preferably 1000-3000% higher.
  • change in cell growth refers to any change in cell growth and proliferation characteristics in vitro or in vivo, such as formation of foci, anchorage independence, semi-solid or soft agar growth, changes in contact inhibition and density limitation of growth, loss of growth factor or serum requirements, changes in cell morphology, gaining or losing immortalization, gaining or losing tumor specific markers, ability to form or suppress tumors when injected into suitable animal hosts, and/or immortalization of the cell. See, e.g., Freshney, Culture of Animal Cells a Manual of Basic Technique -pp. 231-241 (3 rd ed. 1994).
  • Tumor cell refers to precancerous, cancerous, and normal cells in a tumor.
  • Cancer cells “transformed” cells or “transformation” in tissue culture, refers to spontaneous or induced phenotypic changes that do not necessarily involve the uptake of new genetic material. Although transformation can arise from infection with a transforming virus and incorporation of new genomic DNA, or uptake of exogenous DNA, it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation is associated with phenotypic changes, such as immortalization of cells, aberrant growth control, nonmorphological changes, and/or malignancy (see, Freshney, Culture of Animal Cells a Manual of Basic Technique (3 rd ed. 1994)).
  • Antibody refers to a polypeptide comprising a framework region from an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen.
  • the recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes.
  • Light chains are classified as either kappa or lambda.
  • Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in rum define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively.
  • the antigen-binding region of an antibody or its functional equivalent will be most critical in specificity and affinity of binding. See Paul, Fundamental Immunology.
  • An exemplary immunoglobulin (antibody) structural unit comprises a tetramer.
  • Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one "light” (about 25 kD) and one "heavy” chain (about 50-70 kD).
  • the N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition.
  • the terms variable light chain (V L ) and variable heavy chain (V H ) refer to these light and heavy chains respectively.
  • Antibodies exist, e.g., as intact immunoglobulins or as a number of well- characterized fragments produced by digestion with various peptidases.
  • pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab') 2; a dimer of Fab which itself is a light chain joined to V H -C H 1 by a disulfide bond.
  • the F(ab') 2 may be reduced under mild conditions to break the disulfide linkage in the hinge region, thereby converting the F(ab')' 2 dimer into an Fab' monomer.
  • the Fab' monomer is essentially Fab with part of the hinge region (see Fundamental Immunology (Paul ed., 3d ed. 1993). While various antibody fragments are defined in terms of the digestion of an intact antibody, one of skill will appreciate that such fragments may be synthesized de novo either chemically or by using recombinant DNA methodology. Thus, the term antibody, as used herein, also mcludes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e.g., single chain Fv) or those identified using phage display libraries (see, e.g., McCafferty et al, Nature 348:552-554 (1990))
  • Patent 4,946,778 can be adapted to produce antibodies to polypeptides of this invention.
  • transgenic mice, or other organisms such as other mammals may be used to express humanized antibodies.
  • phage display technology can be used to identify antibodies and heteromeric Fab fragments that specifically bind to selected antigens (see, e.g., McCafferty et al, Nature 348:552-554 (1990); Marks et al, Biotechnology 10:779-783 (1992)).
  • a “chimeric antibody” is an antibody molecule in which, e.g, (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and/or species, or an entirely different molecule which confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity.
  • the expression levels of genes are determined in different patient samples for which diagnosis information is desired, to provide expression profiles.
  • An expression profile of a particular sample is essentially a "fingerprint" of the state of the sample; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is characteristic of the state of the cell. That is, normal tissue may be distinguished from cancerous or metastatic cancerous tissue, or metastatic cancerous tissue can be compared with tissue from surviving cancer patients. By comparing expression profiles of tissue in known different metastatic breast cancer or metastatic lung cancer states, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained.
  • sequences that are differentially expressed in metastatic breast cancer or metastatic lung cancer versus non-metastatic breast cancer or non- metastatic lung cancer tissue allows the use of this information in a number of ways. For example, a particular treatment regime may be evaluated: does a chemotherapeutic drag act to down- regulate metastatic breast cancer or metastatic lung cancer, and thus tumor growth or recurrence, in a particular patient. Similarly, diagnosis and treatment outcomes may be done or confirmed by comparing patient samples with the known expression profiles. Metastatic tissue can also be analyzed to determine the stage of metastatic breast cancer or metastatic lung cancer in the tissue.
  • these gene expression profiles allow screening of drug candidates with an eye to mimicking or altering a particular expression profile; e.g., screening can be done for drugs that suppress the metastatic breast cancer or metastatic lung cancer expression profile.
  • screening can be done for drugs that suppress the metastatic breast cancer or metastatic lung cancer expression profile.
  • biochips comprising sets of the important metastatic breast cancer or metastatic lung cancer genes, which can then be used in these screens.
  • PCR methods may be applied with selected primer pairs, and analysis may be of RNA or of genomic sequences. These methods can also be done on the protein basis; that is, protein expression levels of the metastatic breast cancer or metastatic lung cancer proteins can be evaluated for diagnostic purposes or to screen candidate agents.
  • metastatic breast cancer or metastatic lung cancer nucleic acid sequences can be administered for gene therapy purposes, including the administration of antisense nucleic acids, or the metastatic breast cancer or metastatic lung cancer proteins (including antibodies and other modulators thereof) administered as therapeutic drugs or as protein or DNA vaccines.
  • the present invention provides nucleic acid and protein sequences that are differentially expressed in metastatic breast cancer or metastatic lung cancer, herein termed "metastatic breast cancer or metastatic lung cancer sequences.”
  • metastatic breast cancer or metastatic lung cancer sequences include those that are upregulated (i.e., expressed at a higher level) in metastatic breast cancer or metastatic lung cancer, as well as those that are down-regulated (i.e., expressed at a lower level).
  • metastatic breast cancer or metastatic lung cancer sequences are from humans; however, as will be appreciated by those in the art, metastatic breast cancer or metastatic lung cancer sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other metastatic breast cancer or metastatic lung cancer sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc.) and pets (dogs, cats, etc.). Metastatic breast cancer or metastatic lung cancer sequences from other organisms may be obtained using the techniques outlined below.
  • Metastatic breast cancer or metastatic lung cancer sequences can include both nucleic acid and amino acid sequences.
  • metastatic breast cancer or metastatic lung cancer nucleic acid sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes or PCR microtiter plates with selected probes to the metastatic breast cancer or metastatic lung cancer sequences can be generated.
  • a metastatic breast cancer or metastatic lung cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the metastatic breast cancer or metastatic lung cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
  • the metastatic breast cancer or metastatic lung cancer screen typically mcludes comparing genes identified in different tissues, e.g., normal and cancerous tissues, or tumor tissue samples from patients who have metastatic disease vs. non metastatic tissue, or tumor tissue samples from patients who have been diagnosed cancer but have survived vs. metastatic tissue.
  • Other suitable tissue comparisons include comparing metastatic breast cancer or metastatic lung cancer samples with metastatic cancer samples from other cancers, such as gastrointestinal cancers, prostate, ovarian, etc. Samples of, e.g., breast cancer survivor tissue and tissue undergoing metastasis are applied to biochips comprising nucleic acid probes.
  • the samples are first microdissected, if applicable, and treated as is known in the art for the preparation of mRNA.
  • Suitable biochips are commercially available, e.g., GENECHIP ® (DNA microarray) technology from Affymetrix, Inc. (Santa Clara, CA). Gene expression profiles as described herein are generated and the data analyzed.
  • the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, preferably normal colon, but also including, and not limited to lung, heart, brain, liver, breast, kidney, muscle, prostate, small intestine, large intestine, spleen, bone and placenta.
  • those genes identified during the metastatic breast cancer or metastatic lung cancer screen that are expressed in significant amounts in other tissues are removed from the profile, although in some embodiments, this is not necessary. That is, when screening for drags, it is usually preferable that the target be disease specific, to minimize possible side effects.
  • metastatic breast cancer or metastatic lung cancer sequences are those that are up-regulated in metastatic breast cancer or metastatic lung cancer; that is, the expression of these genes is higher in the metastatic tissue as compared to non-metastatic cancerous tissue or normal tissue (see, e.g., Tables 1-3, 6-8, 11-12).
  • Up- regulation means, when the ratio is presented as a number greater than one, that the ratio is greater than one, preferably 1.5 or greater, more preferably 2.0 or greater. All UniGene cluster identification numbers and accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference.
  • metastatic breast cancer or metastatic lung cancer sequences are those that are down-regulated in the metastatic breast cancer or metastatic lung cancer; that is, the expression of these genes is lower in metastatic tissue as compared to non- metastatic cancerous tissue or normal tissue (see, e.g., Tables 4-5 and 9-10).
  • Down- regulation means, when the ratio is presented as a number greater than one, that the ratio is greater than one, preferably 1.5 or greater, more preferably 2.0 or greater, or, when the ratio is presented as a number less than one, that the ratio is less than one, preferably 0.5 or less, more preferably 0.25 or less.
  • the ability to identify genes that are over or under expressed in metastatic breast cancer or metastatic lung cancer can additionally provide high-resolution, high-sensitivity datasets which can be used in the areas of diagnostics, therapeutics, drag development, pharmacogenetics, protein stracture, biosensor development, and other related areas.
  • the expression profiles can be used in diagnostic or prognostic evaluation of patients with metastatic breast cancer or metastatic lung cancer.
  • subcellular toxicological information can be generated to better direct drag stracture and activity correlation (see Anderson, Pharmaceutical Proteomics: Targets, Mechanism, and Function, paper presented at the IBC Proteomics conference, Coronado, CA (June 11-12, 1998)).
  • Subcellular toxicological information can also be utilized in a biological sensor device to predict the likely toxicological effect of chemical exposures and likely tolerable exposure thresholds (see U.S. Patent No. 5,811,231). Similar advantages accrue from datasets relevant to other biomolecules and bioactive agents (e.g., nucleic acids, saccharides, lipids, drags, and the like).
  • bioactive agents e.g., nucleic acids, saccharides, lipids, drags, and the like.
  • the present invention provides a database that includes at least one set of assay data.
  • the data contained in the database is acquired, e.g., using array analysis either singly or in a library format.
  • the database can be in substantially any form in which data can be maintained and transmitted, but is preferably an electronic database.
  • the electronic database of the invention can be maintained on any electronic device allowing for the storage of and access to the database, such as a personal computer, but is preferably distributed on a wide area network, such as the World Wide Web.
  • compositions and methods for identifying and/or quantitating the relative and/or absolute abundance of a variety of molecular and macromolecular species from a biological sample undergoing metastatic breast cancer or metastatic lung cancer i.e., the identification of metastatic breast cancer or metastatic lung cancer-associated sequences described herein, provide an abundance of information, which can be correlated with pathological conditions, predisposition to disease, drag testing, therapeutic monitoring, gene- disease causal linkages, identification of correlates of immunity and physiological status, among others.
  • data generated from the assays of the invention is suited for manual review and analysis, in a preferred embodiment, prior data processing using highspeed computers is utilized.
  • U.S. Patents 6,023,659 and 5,966,712 disclose a relational database system for storing biomolecular sequence information in a manner that allows sequences to be catalogued and searched according to one or more protein function hierarchies.
  • U.S. Patent 5,953,727 discloses a relational database having sequence records containing information in a format that allows a collection of partial-length DNA sequences to be catalogued and searched according to association with one or more sequencing projects for obtaining full-length sequences from the collection of partial length sequences.
  • Patent 5,706,498 discloses a gene database retrieval system for making a retrieval of a gene sequence similar to a sequence data item in a gene database based on the degree of similarity between a key sequence and a target sequence.
  • U.S. Patent 5,538,897 discloses a method using mass spectroscopy fragmentation patterns of peptides to identify amino acid sequences in computer databases by comparison of predicted mass spectra with experimentally-derived mass spectra using a closeness-of-fit measure.
  • U.S. Patent 5,926,818 discloses a multidimensional database comprising a functionality for multi-dimensional data analysis described as on-line analytical processing (OLAP), which entails the consolidation of projected and actual data according to more than one consolidation path or dimension.
  • OLAP on-line analytical processing
  • Patent 5,295,261 reports a hybrid database structure in which the fields of each database record are divided into two classes, navigational and informational data, with navigational fields stored in a hierarchical topological map which can be viewed as a tree structure or as the merger of two or more such tree structures.
  • Bioinformatics A Practical Guide to the Analysis of Genes and Proteins (Baxevanis & Oeullette eds., 1998)); Rashidi & Buehler, Bioinformatics: Basic Applications in Biological Science and Medicine (1999); Introduction to Computational Molecular Biology (Setubal et al., eds 1997); Bioinformatics: Methods and Protocols (Misener & Krawetz, eds, 2000); Bioinformatics: Sequence, Structure, and Databanks: A Practical Approach (Higgins & Taylor, eds., 2000); Brown, Bioinformatics: A Biologist's Guide to Biocomputing and the Internet (2001); Han & Kamber, Data Mining: Concepts and Techniques (2000); and Waterman, Introduction to Computational Biology: Maps, Sequences, and Genomes (1995).
  • the present invention provides a computer database comprising a computer and software for storing in computer-retrievable form assay data records cross-tabulated, e.g., with data specifying the source of the target-containing sample from which each sequence specificity record was obtained.
  • At least one of the sources of target-containing sample is from a control tissue sample known to be free of pathological disorders.
  • at least one of the sources is a known pathological tissue specimen, e.g., a neoplastic lesion or another tissue specimen to be analyzed for metastatic breast cancer or metastatic lung cancer.
  • the assay records cross-tabulate one or more of the following parameters for each target species in a sample: (1) a unique identification code, which can include, e.g., a target molecular stracture and/or characteristic separation coordinate (e.g., electrophoretic coordinates); (2) sample source; and (3) absolute and/or relative quantity of the target species present in the sample.
  • the invention also provides for the storage and retrieval of a collection of target data in a computer data storage apparatus, which can include magnetic disks, optical disks, magneto-optical disks, DRAM, SRAM, SGRAM, SDRAM, RDRAM, DDR RAM, magnetic bubble memory devices, and other data storage devices, including CPU registers and on-CPU data storage arrays.
  • the target data records are stored as a bit pattern in an array of magnetic domains on a magnetizable medium or as an array of charge states or transistor gate states, such as an array of cells in a DRAM device (e.g., each cell comprised of a transistor and a charge storage area, which may be on the transistor).
  • the invention provides such storage devices, and computer systems built therewith, comprising a bit pattern encoding a protein expression fingerprint record comprising unique identifiers for at least 10 target data records cross-tabulated with target source.
  • the invention preferably provides a method for identifying related peptide or nucleic acid sequences, comprising performing a computerized comparison between a peptide or nucleic acid sequence assay record stored in or retrieved from a computer storage device or database and at least one other sequence.
  • the comparison can include a sequence analysis or comparison algorithm or computer program embodiment thereof (e.g., FASTA, TFASTA, GAP, BESTFIT) and/or the comparison may be of the relative amount of a peptide or nucleic acid sequence in a pool of sequences determined from a polypeptide or nucleic acid sample of a specimen.
  • the invention also preferably provides a magnetic disk, such as an IBM-compatible (DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g., Linux, SunOS, Solaris, ATX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or hard (fixed, Winchester) disk drive, comprising a bit pattern encoding data from an assay of the invention in a file format suitable for retrieval and processing in a computerized sequence analysis, comparison, or relative quantitation method.
  • a magnetic disk such as an IBM-compatible (DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g., Linux, SunOS, Solaris, ATX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or hard (fixed, Winchester) disk drive, comprising a bit pattern encoding data from an assay of the invention in a file format suitable for retrieval and processing
  • the invention also provides a network, comprising a plurality of computing devices linked via a data link, such as an Ethernet cable (coax or lOBaseT), telephone line, ISDN line, wireless network, optical fiber, or other suitable signal transmission medium, whereby at least one network device (e.g., computer, disk array, etc.) comprises a pattern of magnetic domains (e.g., magnetic disk) and or charge domains (e.g., an array of DRAM cells) composing a bit pattern encoding data acquired from an assay of the invention.
  • a network device e.g., computer, disk array, etc.
  • a pattern of magnetic domains e.g., magnetic disk
  • charge domains e.g., an array of DRAM cells
  • the invention also provides a method for transmitting assay data that mcludes generating an electronic signal on an electronic communications device, such as a modem, ISDN terminal adapter, DSL, cable modem, ATM switch, or the like, wherein the signal includes (in native or encrypted format) a bit pattern encoding data from an assay or a database comprising a plurality of assay results obtained by the method of the invention.
  • an electronic communications device such as a modem, ISDN terminal adapter, DSL, cable modem, ATM switch, or the like
  • the signal includes (in native or encrypted format) a bit pattern encoding data from an assay or a database comprising a plurality of assay results obtained by the method of the invention.
  • the invention provides a computer system for comparing a query target to a database containing an array of data structures, such as an assay result obtained by the method of the invention, and ranking database targets based on the degree of identity and gap weight to the target data.
  • a central processor is preferably initialized to load and execute the computer program for alignment and/or comparison of the assay results.
  • Data for a query target is entered into the central processor via an I/O device.
  • Execution of the computer program results in the central processor retrieving the assay data from the data file, which comprises a binary description of an assay result.
  • the target data or record and the computer program can be transferred to secondary memory, which is typically random access memory (e.g., DRAM, SRAM, SGRAM, or SDRAM).
  • Targets are ranked according to the degree of correspondence between a selected assay characteristic (e.g., binding to a selected affinity moiety) and the same characteristic of the query target and results are output via an I/O device.
  • a central processor can be a conventional computer (e.g., Intel Pentium, PowerPC, Alpha, PA-8000, SPARC, MIPS 4400, MIPS 10000, VAX, etc.);
  • a program can be a commercial or public domain molecular biology software package (e.g., UWGCG Sequence Analysis Software, Darwin);
  • a data file can be an optical or magnetic disk, a data server, a memory device (e.g., DRAM, SRAM, SGRAM, SDRAM, EPROM, bubble memory, flash memory, etc.);
  • an I O device can be a terminal comprising a video display and a keyboard, a modem, an ISDN terminal adapter, an Ethernet port, a punched card reader, a magnetic strip reader, or other suitable I/O device.
  • the invention also preferably provides the use of a computer system, such as that described above, which comprises: (1) a computer; (2) a stored bit pattern encoding a collection of peptide sequence specificity records obtained by the methods of the invention, which may be stored in the computer; (3) a comparison target, such as a query target; and (4) a program for alignment and comparison, typically with rank-ordering of comparison results on the basis of computed similarity values.
  • a computer system such as that described above, which comprises: (1) a computer; (2) a stored bit pattern encoding a collection of peptide sequence specificity records obtained by the methods of the invention, which may be stored in the computer; (3) a comparison target, such as a query target; and (4) a program for alignment and comparison, typically with rank-ordering of comparison results on the basis of computed similarity values.
  • Metastatic breast cancer or metastatic lung cancer proteins of the present invention may be classified as secreted proteins, transmembrane proteins or intracellular proteins.
  • the metastatic breast cancer or metastatic lung cancer protein is an intracellular protein. Intracellular proteins may be found in the cytoplasm and/or in the nucleus and/or in the organelles. Proteins containing one or more transmembrane domains that exclusively reside in organelles are also considered intracellular proteins.
  • Intracellular proteins are involved in all aspects of cellular function and replication (including, e.g., signaling pathways); aberrant expression of such proteins often results in unregulated or disregulated cellular processes (see, e.g., Molecular Biology of the Cell (Alberts, ed., 3rd ed., 1994).
  • many intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity, polymerase activity and the like.
  • Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various subcellular localizations, and are involved in maintaining the structural integrity of organelles.
  • Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner.
  • PTB domains which are distinct from SH2 domains, also bind tyrosine phosphorylated targets.
  • SH3 domains bind to proline-rich targets.
  • PH domains, tetratricopeptide repeats and WD domains have been shown to mediate protein-protein interactions.
  • Pfam protein families
  • Pfam protein families
  • the metastatic breast cancer or metastatic lung cancer sequences are transmembrane proteins.
  • Transmembrane proteins are molecules that span a phospholipid bilayer of a cell. They may have an intracellular domain, an extracellular domain, or both. The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular domain may have enzymatic activity and/or may serve as a binding site for additional proteins.
  • transmembrane proteins may contain from one to many transmembrane domains.
  • receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/tlireonme protein kinases contain a single transmembrane domain.
  • various other proteins including channels, pumps, and adenylyl cyclases contain numerous transmembrane domains.
  • GPCRs G protem coupled receptors
  • extracellular domains of transmembrane proteins are diverse; however, conserved motifs are found repeatedly among various extracellular domains. conserveed structure and/or functions have been ascribed to different extracellular motifs. Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are found on receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF and PDGF are circulating growth factors that bind to their cognate receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, hormones, neurotrophic factors and the like.
  • Extracellular domains also bind to cell-associated molecules, hi this respect, they mediate cell-cell interactions.
  • Cell-associated ligands can be tethered to the cell, e.g., via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins.
  • Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.
  • transmembrane proteins are particularly preferred in the present invention as they are readily accessible targets for extracellular immunotherapeutics, as are described herein.
  • transmembrane proteins can be also useful in imaging modalities.
  • Antibodies may be used to label such readily accessible proteins in situ or in histological analysis. Alternatively, antibodies can also label intracellular proteins, in which case analytical samples are typically permeablized to provide access to intracellular proteins.
  • transmembrane protein can be made soluble by removing transmembrane sequences, e.g., tlirough recombinant methods.
  • transmembrane proteins that have been made soluble can be made to be secreted through recombinant means by adding an appropriate signal sequence.
  • the metastatic breast cancer or metastatic lung cancer proteins are secreted proteins; the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway.
  • Secreted proteins are involved in numerous physiological events; by virtue of their circulating nature, they often serve to transmit signals to various other cell types.
  • the secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor) or an endocrine manner (acting on cells at a distance).
  • Metastatic breast cancer or metastatic lung cancer proteins that are secreted proteins are particularly preferred in the present invention as they serve as good targets for diagnostic markers, e.g., for blood, plasma, serum, or stool tests.
  • metastatic breast cancer or metastatic lung cancer sequence is initially identified by substantial nucleic acid and/or amino acid sequence homology or linkage to the metastatic breast cancer or metastatic lung cancer sequences outlined herein.
  • Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
  • linked sequences on a mRNA are found on the same molecule.
  • the metastatic breast cancer or metastatic lung cancer nucleic acid sequences of the invention can be fragments of larger genes, i.e., they are nucleic acid segments. "Genes" in this context includes coding regions, non-coding regions, and mixtures of coding and non-coding regions. Accordingly, as will be appreciated by those in the art, using the sequences provided herein, extended sequences, in either direction, of the metastatic breast cancer or metastatic lung cancer genes can be obtained, using techniques well known in the art for cloning either longer sequences or the full length sequences; see Ausubel, et al, supra. Much can be done by informatics and many sequences can be clustered to include multiple sequences corresponding to a single gene, e.g., systems such as UniGene.
  • the metastatic breast cancer or metastatic lung cancer nucleic acid Once the metastatic breast cancer or metastatic lung cancer nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombined to form the entire metastatic breast cancer or metastatic lung cancer nucleic acid coding regions or the entire mRNA sequence.
  • the recombinant metastatic breast cancer or metastatic lung cancer nucleic acid can be further- used as a probe to identify and isolate other metastatic breast cancer or metastatic lung cancer nucleic acids, e.g., extended coding regions. It can also be used as a "precursor" nucleic acid to make modified or variant metastatic breast cancer or metastatic lung cancer nucleic acids and proteins.
  • metastatic breast cancer or metastatic lung cancer nucleic acids of the present invention are used in several ways.
  • nucleic acid probes to the metastatic breast cancer or metastatic lung cancer nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, e.g., for gene therapy, vaccine, and/or antisense applications.
  • the metastatic breast cancer or metastatic lung cancer nucleic acids that include coding regions of metastatic breast cancer or metastatic lung cancer proteins can be put into expression vectors for the expression of metastatic breast cancer or metastatic lung cancer proteins, again for screening purposes or for administration to a patient.
  • nucleic acid probes to metastatic breast cancer or metastatic lung cancer nucleic acids are made.
  • the nucleic acid probes attached to the biochip are designed to be substantially complementary to the metastatic breast cancer or metastatic lung cancer nucleic acids, i.e. the target sequence (either the target sequence of the sample or to other probe sequences, e.g., in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs.
  • this complementarity need not be perfect; there may be any number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention.
  • the sequence is not a complementary target sequence.
  • substantially complementary herein is meant that the probes are sufficiently complementary to the target sequences to hybridize under appropriate reaction conditions, particularly high stringency conditions, as outlined herein.
  • a nucleic acid probe is generally single stranded but can be partially single and partially double stranded.
  • the strandedness of the probe is dictated by the stracture, composition, and properties of the target sequence.
  • the nucleic acid probes range from about 8 to about 100 bases long, with from about 10 to about 80 bases being preferred, and from about 30 to about 50 bases being particularly preferred. That is, generally complements of ORFs or whole genes are not used.
  • nucleic acids of lengths up to hundreds of bases can be used.
  • more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used. That is, two, three, four or more probes, with three being preferred, are used to build in a redundancy for a particular target.
  • the probes can be overlapping (i.e., have some sequence in common), or separate.
  • PCR primers may be used to amplify signal for higher sensitivity.
  • nucleic acids can be attached or immobilized to a solid support in a wide variety of ways.
  • immobilized and grammatical equivalents herein is meant the association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined below.
  • the binding can typically be covalent or non-covalent.
  • non- covalent binding and grammatical equivalents herein is typically meant one or more of electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non- covalent binding of the biotinylated probe to the streptavidin.
  • covalent binding and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds. Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Immobilization may also involve a combination of covalent and non-covalent interactions.
  • the probes are attached to a biochip in a wide variety of ways, as will be appreciated by those in the art.
  • the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be directly synthesized on the biochip.
  • the biochip comprises a suitable solid substrate.
  • substrate or “solid support” or other grammatical equivalents herein is meant a material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method.
  • the number of possible substrates are very large, and include, but are not limited to, glass and modified or fiinctionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, Teflon, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica- based materials including silicon and modified silicon, carbon, metals, inorganic glasses, plastics, etc.
  • the substrates allow optical detection and do not appreciably fluoresce.
  • a preferred substrate is described in copending application entitled Reusable Low Fluorescent Plastic Biochip, U.S. Application Serial No. 09/270,214, filed March 15, 1999, herein incorporated by reference in its entirety.
  • the substrate is planar, although as will be appreciated by those in the art, other configurations of substrates may be used as well.
  • the probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume.
  • the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics.
  • the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two.
  • the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly preferred.
  • the probes can be attached using functional groups on the probes.
  • nucleic acids containing amino groups can be attached to surfaces comprising amino groups, e.g., using linkers as are known in the art; e.g., homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross-linkers, pages 155-200).
  • oligonucleotides are synthesized as is known in the art, and then attached to the surface of the solid support. As will be appreciated by those skilled in the art, either the 5 ' or 3 ' terminus may be attached to the solid support, or attachment may be via an internal nucleoside.
  • the immobilization to the solid support may be very strong, yet non-covalent.
  • biotinylated oligonucleotides can be made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.
  • the oligonucleotides may be synthesized on the surface, as is known in the art.
  • photoactivation techniques utilizing photopolymerization compounds and techniques are used.
  • the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO 95/35505; U.S. Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which are expressly incorporated by reference; these methods of attachment form the basis of the GENECHIP ® (DNA microarray) technology from Affymetrix, Inc. (Santa Clara, CA).
  • amplification-based assays are performed to measure the expression level of metastatic breast cancer or metastatic lung cancer-associated sequences. These assays are typically performed in conjunction with reverse transcription.
  • a metastatic breast cancer or metastatic lung cancer-associated nucleic acid sequence acts as a template in an amplification reaction (e.g., Polymerase Chain Reaction, or PCR).
  • an amplification reaction e.g., Polymerase Chain Reaction, or PCR
  • the amount of amplification product will be proportional to the amount of template in the original sample.
  • Comparison to appropriate controls provides a measure of the amount of metastatic breast cancer or metastatic lung cancer-associated RNA.
  • Methods of quantitative amplification are well known to those of skill in the art. Detailed protocols for quantitative PCR are provided, e.g., in Innis et al. , PCR Protocols, A Guide to Methods and Applications (1990).
  • a TAQMAN ® (PCR reagent kit) based assay is used to measure expression.
  • TAQMAN ® (PCR reagent kit) based assays use a fluorogenic oligonucleotide probe that contains a 5' fluorescent dye and a 3' quenching agent. The probe hybridizes to a PCR product, but cannot itself be extended due to a blocking agent at the 3 ' end.
  • the 5' nuclease activity of the polymerase e.g., AMPLITAQ ® (PCR enzyme reagent)
  • metastatic breast cancer or metastatic lung cancer nucleic acids e.g., encoding metastatic breast cancer or metastatic lung cancer proteins
  • expression vectors and recombinant DNA technology are well known to those of skill in the art (see, e.g., Ausubel, supra, and Gene Expression Systems (Fernandez & Hoeffler, eds, 1999)) and are used to express proteins.
  • the expression vectors may be either self- replicating extrachromosomal vectors or vectors which integrate into a host genome.
  • control sequences refers to DNA sequences used for the expression of an operably linked coding sequence in a particular host organism.
  • Control sequences that are suitable for prokaryotes, e.g., include a promoter, optionally an operator sequence, and a ribosome binding site.
  • Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
  • Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence.
  • DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide;
  • a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or
  • a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation.
  • "operably linked” means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase.
  • Enhancers do not have to be contiguous. Linking is typically accomplished by ligation at convenient restriction sites. If such sites do not exist, synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice.
  • Transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the metastatic breast cancer or metastatic lung cancer protein. Numerous types of appropriate expression vectors, and suitable regulatory sequences are known in the art for a variety of host cells.
  • transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences.
  • the regulatory sequences include a promoter and transcriptional start and stop sequences.
  • Promoter sequences encode either constitutive or inducible promoters.
  • the promoters may be either naturally occurring promoters or hybrid promoters.
  • Hybrid promoters which combine elements of more than one promoter, are also known in the art, and are useful in the present invention.
  • an expression vector may comprise additional elements.
  • the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, e.g., in mammalian or insect cells for expression and in a procaryotic host for cloning and amplification.
  • the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct.
  • the integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for integrating vectors are well known in the art (e.g., Fernandez & Hoeffler, supra).
  • the expression vector contains a selectable marker gene to allow the selection of transformed host cells.
  • Selection genes are well known in the art and will vary with the host cell used.
  • the metastatic breast cancer or metastatic lung cancer proteins of the present invention are produced by culturmg a host cell transformed with an expression vector containing nucleic acid encoding a metastatic breast cancer or metastatic lung cancer protein, under the appropriate conditions to induce or cause expression of the metastatic breast cancer or metastatic lung cancer protein.
  • Conditions appropriate for metastatic breast cancer or metastatic lung cancer protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained by one skilled in the art through routine experimentation or optimization.
  • the use of constitutive promoters in the expression vector will require optimizing the growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction.
  • the timing of the harvest is important.
  • the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial for product yield.
  • Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect and animal cells, including mammalian cells. Of particular interest are Saccharomyces cerevisiae and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, HUVEC (human umbilical vein endothelial cells), THP1 cells (a macrophage cell line) and various other human cells and cell lines.
  • the metastatic breast cancer or metastatic lung cancer proteins are expressed in mammalian cells.
  • Mammalian expression systems are also known in the art, and include retroviral and adenoviral systems.
  • mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the SV40 early promoter, mouse mammary tumor virus LTR promoter, adenovirus major late promoter, herpes simplex virus promoter, and the CMV promoter (see, e.g., Fernandez & Hoeffler, supra).
  • transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3' to the translation stop codon and thus, together with the promoter elements, flank the coding sequence.
  • transcription terminator and polyadenylation signals include those derived form SV40.
  • metastatic breast cancer or metastatic lung cancer proteins are expressed in bacterial systems. Promoters from bacteriophage may also be used and are known in the art. In addition, synthetic promoters and hybrid promoters are also useful; e.g., the tac promoter is a hybrid of the tip and lac promoter sequences. Furthermore, a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. In addition to a functioning promoter sequence, an efficient ribosome binding site is desirable.
  • the expression vector may also include a signal peptide sequence that provides for secretion of the metastatic breast cancer or metastatic lung cancer protein in bacteria.
  • the protein is either secreted into the growth media (gram-positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria).
  • the bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed. Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin and tetracycline. Selectable markers also include biosynthetic genes, such as those in the histidine, tryptophan and leucine biosynthetic pathways. These components are assembled into expression vectors. Expression vectors for bacteria are well known in the art, and include vectors for Bacillus subtilis, E.
  • the bacterial expression vectors are transformed into bacterial host cells using techniques well known in the art, such as calcium chloride treatment, electroporation, and others.
  • metastatic breast cancer or metastatic lung cancer proteins are produced in insect cells.
  • Expression vectors for the transformation of insect cells, and in particular, baculovirus-based expression vectors, are well known in the art.
  • metastatic breast cancer or metastatic lung cancer protein is produced in yeast cells.
  • Yeast expression systems are well known in the art, and include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis sn.dK. lactis, Pichia guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yarrowia lipolytica.
  • the metastatic breast cancer or metastatic lung cancer protein may also be made as a fusion protein, using techniques well known in the art.
  • the metastatic breast cancer or metastatic lung cancer protein may be fused to a carrier protein to form an immunogen.
  • the metastatic breast cancer or metastatic lung cancer protein may be made as a fusion protein to increase expression for affinity purification purposes, or for other reasons.
  • the metastatic breast cancer or metastatic lung cancer protein is a metastatic breast cancer or metastatic lung cancer peptide
  • the nucleic acid encoding the peptide may be linked to other nucleic acid for expression purposes.
  • the metastatic breast cancer or metastatic lung cancer protein is purified or isolated after expression.
  • Metastatic breast cancer or metastatic lung cancer proteins may be isolated or purified in a variety of appropriate ways. Standard purification methods include electrophoretic, molecular, immunological and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing.
  • the metastatic breast cancer or metastatic lung cancer protein may be purified using a standard anti-metastatic breast cancer or metastatic lung cancer protein antibody column. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. For general guidance in suitable purification techniques, see Scopes, Protein Purification (1982). The degree of purification necessary will vary depending on the use of the metastatic breast cancer or metastatic lung cancer protein. In some instances no purification will be necessary.
  • metastatic breast cancer or metastatic lung cancer proteins and nucleic acids are useful in a number of applications. They may be used as immunoselection reagents, as vaccine reagents, as screening agents, etc.
  • the metastatic breast cancer or metastatic lung cancer proteins are derivative or variant metastatic breast cancer or metastatic lung cancer proteins as compared to the wild-type sequence. That is, as outlined more fully below, the derivative metastatic breast cancer or metastatic lung cancer peptide will often contain at least one amino acid substitution, deletion or insertion, with amino acid substitutions being particularly preferred. The amino acid substitution, insertion or deletion may occur at a particular residue within the metastatic breast cancer or metastatic lung cancer peptide. Also included within one embodiment of metastatic breast cancer or metastatic lung cancer proteins of the present invention are amino acid sequence variants. These variants typically fall into one or more of three classes: substitutional, insertional or deletional variants.
  • variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the metastatic breast cancer or metastatic lung cancer protein, using cassette or PCR mutagenesis or other techniques, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above.
  • variant metastatic breast cancer or metastatic lung cancer protein fragments having up to about 100-150 residues may be prepared by in vitro synthesis.
  • Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the metastatic breast cancer or metastatic lung cancer protein amino acid sequence.
  • the variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics as will be more fully outlined below.
  • the mutation per se need not be predetermined.
  • random mutagenesis may be conducted at the target codon or region and the expressed metastatic breast cancer or metastatic lung cancer variants screened for the optimal combination of desired activity.
  • Techniques exist for making substitution mutations at predetermined sites in DNA having a known sequence e.g., M13 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of metastatic breast cancer or metastatic lung cancer protein activities.
  • Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1 to 20 amino acids, although considerably larger insertions may be occasionally tolerated. Deletions range from about 1 to about 20 residues, although in some cases deletions may be much larger.
  • substitutions, deletions, insertions or any combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. Larger changes may be tolerated in certain circumstances. When small alterations in the characteristics of a metastatic breast cancer or metastatic lung cancer protein are desired, substitutions are generally made in accordance with the amino acid substitution chart provided in the definition section.
  • Variants typically exhibit the same qualitative biological activity and will elicit the same immune response as the naturally-occurring analog, although variants also are selected to modify the characteristics of the metastatic breast cancer or metastatic lung cancer proteins as needed.
  • the variant may be designed or reorganized such that the biological activity of the metastatic breast cancer or metastatic lung cancer protein is altered. For example, glycosylation sites may be altered or removed.
  • Covalent modifications of metastatic breast cancer or metastatic lung cancer polypeptides are included within the scope of this invention.
  • One type of covalent modification includes reacting targeted amino acid residues of a metastatic breast cancer or metastatic lung cancer polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of a metastatic breast cancer or metastatic lung cancer polypeptide.
  • Derivatization with bifunctional agents is useful, for instance, for crosslinking metastatic breast cancer or metastatic lung cancer polypeptides to a water-insoluble support matrix or surface for use in the method for purifying anti-metastatic breast cancer or metastatic lung cancer polypeptide antibodies or screening assays, as is more fully described below.
  • crosslinking agents include, e.g., l,l-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, e.g., esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido-l,8-octane and agents such as methyl-3-((p- azidophenyl)dithio)propioimidate.
  • l,l-bis(diazoacetyl)-2-phenylethane glutaraldehyde
  • N-hydroxysuccinimide esters e.g., esters with 4-azidosalicylic acid
  • homobifunctional imidoesters including disuccinimidyl esters such as 3,
  • Another type of covalent modification of the metastatic breast cancer or metastatic lung cancer polypeptide encompassed by this invention is an altered native glycosylation pattern of the polypeptide.
  • "Altering the native glycosylation pattern” is intended herein to mean adding to or deleting one or more carbohydrate moieties of a native sequence metastatic breast cancer or metastatic lung cancer polypeptide.
  • Glycosylation patterns can be altered in many ways. For example the use of different cell types to express metastatic breast cancer or metastatic lung cancer-associated sequences can result in different glycosylation patterns.
  • Addition of glycosylation sites to metastatic breast cancer or metastatic lung cancer polypeptides may also be accomplished by altering the amino acid sequence thereof.
  • the alteration may be made, e.g., by the addition of, or substitution by, one or more serine or threonine residues to the native sequence metastatic breast cancer or metastatic lung cancer polypeptide (for 0-linked glycosylation sites).
  • the metastatic breast cancer or metastatic lung cancer amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the metastatic breast cancer or metastatic lung cancer polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
  • Another means of increasing the number of carbohydrate moieties on the metastatic breast cancer or metastatic lung cancer polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e.g., in WO 87/05330, and in Aplin & Wriston, CRC Crit. Rev. Biochem., pp. 259-306 (1981).
  • Removal of carbohydrate moieties present on the metastatic breast cancer or metastatic lung cancer polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation.
  • Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al, Arch. Biochem. Biophys., 259:52 (1987) and by Edge et al, Anal. Biochem., 118:131 (1981).
  • Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo-and exo-glycosidases as described by Thotakura et al, Meth. Enzymol., 138:350 (1987).
  • Another type of covalent modification of metastatic breast cancer or metastatic lung cancer comprises linking the metastatic breast cancer or metastatic lung cancer polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337, each of which is hereby incorporated by reference herein.
  • nonproteinaceous polymers e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes
  • Metastatic breast cancer or metastatic lung cancer polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising a metastatic breast cancer or metastatic lung cancer polypeptide fused to another, heterologous polypeptide or amino acid sequence.
  • such a chimeric molecule comprises a fusion of a metastatic breast cancer or metastatic lung cancer polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind.
  • the epitope tag is generally placed at the amino-or carboxyl-terminus of the metastatic breast cancer or metastatic lung cancer polypeptide.
  • the presence of such epitope-tagged forms of a metastatic breast cancer or metastatic lung cancer polypeptide can be detected using an antibody against the tag polypeptide.
  • provision of the epitope tag enables the metastatic breast cancer or metastatic lung cancer polypeptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag.
  • the chimeric molecule may comprise a fusion of a metastatic breast cancer or metastatic lung cancer polypeptide with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule.
  • tag polypeptides and their respective antibodies are well known and examples include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly) tags; HIS6 and metal chelation tags, the flu HA tag polypeptide and its antibody 12CA5 (Field et al, Mol. Cell. Biol. 8:2159-2165 (1988)); the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10 antibodies thereto (Evan et al, Molecular and Cellular Biology 5:3610-3616 (1985)); and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody (Paborsky et al,
  • tag polypeptides include the Flag-peptide (Hopp et al, BioTechnology 6: 1204-1210 (1988)); the KT3 epitope peptide (Martin et al, Science 255:192-194 (1992)); rubulin epitope peptide (Skinner et al, J. Biol. Chem. 266:15163-15166 (1991)); and the T7 gene 10 protein peptide tag (Lutz-Freyermuth et al, Proc. Natl Acad. Sci. USA 87:6393-6397 (1990)).
  • probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related metastatic breast cancer or metastatic lung cancer proteins from primates or other organisms.
  • probe or degenerate polymerase chain reaction (PCR) primer sequences include unique areas of the metastatic breast cancer or metastatic lung cancer nucleic acid sequence.
  • preferred PCR primers are from about 15 to about 35 nucleotides in length, with from about 20 to about 30 being preferred, and may contain inosine as needed.
  • PCR reaction conditions are well known in the art (e.g., Innis, PCR Protocols, supra).
  • the metastatic breast cancer or metastatic lung cancer protein when a metastatic breast cancer or metastatic lung cancer protein is to be used to generate antibodies, e.g., for immunotherapy or immunodiagnosis, the metastatic breast cancer or metastatic lung cancer protein should share at least one epitope or determinant with the full length protein.
  • epitope or “determinant” herein is typically meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC.
  • antibodies made to a smaller metastatic breast cancer or metastatic lung cancer protein will be able to bind to the full-length protein, particularly linear epitopes.
  • the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross- reactivity.
  • Polyclonal antibodies can be raised in a mammal, e.g., by one or more injections of an immunizing agent and, if desired, an adjuvant.
  • an immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections.
  • the immunizing agent may include a protem encoded by a nucleic acid of Tables 1-12 or fragment thereof or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized.
  • Immunogenic proteins include, e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor.
  • Adjuvants include, e.g., Freund's complete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate).
  • the immunization protocol may be selected by one skilled in the art.
  • the antibodies may, alternatively, be monoclonal antibodies.
  • Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler & Milstein, Nature 256:495 (1975).
  • a hybridoma method a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent.
  • the lymphocytes may be immunized in vitro.
  • the immunizing agent will typically include a polypeptide encoded by a nucleic acid of Tables 1- 12, or fragment thereof, or a fusion protein thereof.
  • peripheral blood lymphocytes are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired.
  • the lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (1986)).
  • Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and primate origin. Usually, rat or mouse myeloma cell lines are employed.
  • the hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells.
  • a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells.
  • the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.
  • the antibodies are bispecific antibodies.
  • Bispecific antibodies are typically monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens or that have binding specificities for two epitopes on the same antigen.
  • one of the binding specificities is for a protein encoded by a nucleic acid of Tables 1-12 or a fragment thereof, the other one is for any other antigen, and preferably for a cell-surface protem or receptor or receptor subunit, preferably one that is tumor specific.
  • tetramer-type technology may create multivalent reagents.
  • the antibodies to metastatic breast cancer or metastatic lung cancer protein are capable of reducing or eliminating a biological function of a metastatic breast cancer or metastatic lung cancer protein, as is described below. That is, the addition of anti-metastatic breast cancer or metastatic lung cancer protein antibodies (either polyclonal or preferably monoclonal) to metastatic breast cancer or metastatic lung cancer tissue (or cells containing metastatic breast cancer or metastatic lung cancer) may reduce or eliminate the metastatic breast cancer or metastatic lung cancer. Generally, at least a 25% decrease in activity, growth, size or the like is preferred, with at least about 50% being particularly preferred and about a 95-100%) decrease being especially preferred.
  • the antibodies to the metastatic breast cancer or metastatic lung cancer proteins are humanized antibodies (e.g., Xenerex Biosciences, Mederex, Inc., Abgenix, Inc., Protein Design Labs, Inc.)
  • Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin.
  • Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity.
  • CDR complementary determining region
  • donor antibody non-human species
  • Fv framework residues of the human immunoglobulin are replaced by corresponding non- human residues.
  • Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences.
  • a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non- human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin consensus sequence.
  • the humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al, Nature 321 :522-525 (1986); Riechmann et al, Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992)).
  • Humanization can be essentially performed following the method of Winter and co-workers (Jones et al, Nature 321:522-525 (1986); Riechmann et al, Nature 332:323-327 (1988); Verhoeyen et al, Science 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody.
  • rodent CDRs or CDR sequences for the corresponding sequences of a human antibody.
  • humanized antibodies are chimeric antibodies (U.S. Patent No. 4,816,567, which is hereby incorporated by reference herein.), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species.
  • Human-like antibodies can also be produced using various techniques known in the art, including phage display libraries (Hoogenboom & Winter, J. Mol. Biol. 227:381 (1991); Marks et al, J. Mol. Biol. 222:581 (1991)).
  • the techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al, Monoclonal Antibodies and Cancer Therapy, p. 77 (1985) and Boerner et al, J. Immunol. 147(l):86-95 (1991)).
  • human antibodies can be made by introducing of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in virtually all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, e.g., in U.S. Patent Nos.
  • immunotherapy is meant treatment of metastatic breast cancer or metastatic lung cancer with an antibody raised against a metastatic breast cancer or metastatic lung cancer proteins.
  • immunotherapy can be passive or active. Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient). Active immunization is the induction of antibody and/or T-cell responses in a recipient (patient). Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised.
  • the antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and under conditions for expression of the antigen, leading to an immune response.
  • metastatic breast cancer or metastatic lung cancer proteins against which antibodies are raised are secreted proteins as described above.
  • antibodies used for treatment bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted metastatic breast cancer or metastatic lung cancer protein.
  • the metastatic breast cancer or metastatic lung cancer protein to which antibodies are raised is a transmembrane protein.
  • antibodies used for this treatment typically bind the extracellular domain of the metastatic breast cancer or metastatic lung cancer protein and prevent it from binding to other proteins, such as circulating ligands or cell-associated molecules.
  • the antibody may cause down-regulation of the transmembrane metastatic breast cancer or metastatic lung cancer protein.
  • the antibody may be a competitive, non-competitive or uncompetitive inhibitor of protein binding to the extracellular domain of the metastatic breast cancer or metastatic lung cancer protein.
  • the antibody may be an antagonist of the metastatic breast cancer or metastatic lung cancer protem or may prevent activation of the transmembrane metastatic breast cancer or metastatic lung cancer protein.
  • the antibody when the antibody prevents the binding of other molecules to the metastatic breast cancer or metastatic lung cancer protein, the antibody prevents growth of the cell.
  • the antibody may also be used to target or sensitize the cell to cytotoxic agents, including, but not limited to TNF- ⁇ , TNF- ⁇ , IL-1, INF- ⁇ and IL-2, or chemotherapeutic agents including 5FU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like.
  • the antibody belongs to a sub-type that activates serum complement when complexed with the transmembrane protein thereby mediating cytotoxicity or antigen-dependent cytotoxicity (ADCC).
  • ADCC antigen-dependent cytotoxicity
  • metastatic breast cancer or metastatic lung cancer is treated by administering to a patient antibodies directed against the transmembrane metastatic breast cancer or metastatic lung cancer protein.
  • Antibody-labeling may activate a co-toxin, localize a toxin payload, or otherwise provide means to locally ablate cells.
  • the antibody is conjugated to an effector moiety.
  • the effector moiety can be any number of molecules, including labeling moieties such as radioactive labels or fluorescent labels, or can be a therapeutic moiety.
  • the therapeutic moiety is a small molecule that modulates the activity of the metastatic breast cancer or metastatic lung cancer protein.
  • the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the metastatic breast cancer or metastatic lung cancer protein.
  • the therapeutic moiety may inhibit enzymatic activity such as protease or collagenase activity associated with metastatic breast cancer or metastatic lung cancer.
  • the therapeutic moiety can also be a cytotoxic agent.
  • targeting the cytotoxic agent to metastatic breast cancer or metastatic lung cancer tissue or cells results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with metastatic breast cancer or metastatic lung cancer.
  • Cytotoxic agents are numerous and varied and include, but are not limited to, cytotoxic drags or toxins or active fragments of such toxins. Suitable toxins and their corresponding fragments include diphtheria A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, enomycin and the like.
  • Cytotoxic agents also include radiochemicals made by conjugating radioisotopes to antibodies raised against metastatic breast cancer or metastatic lung cancer proteins, or binding of a radionuclide to a chelating agent that has been covalently attached to the antibody.
  • Targeting the therapeutic moiety to transmembrane metastatic breast cancer or metastatic lung cancer proteins not only serves to increase the local concentration of therapeutic moiety in the metastatic breast cancer or metastatic lung cancer afflicted area, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety.
  • the metastatic breast cancer or metastatic lung cancer protein against which the antibodies are raised is an intracellular protein.
  • the antibody may be conjugated to a protein or other entity which facilitates entry into the cell.
  • the antibody enters the cell by endocytosis.
  • a nucleic acid encoding the antibody is administered to the individual or cell.
  • an antibody thereto contains a signal for that target localization, i.e., a nuclear localization signal.
  • metastatic breast cancer or metastatic lung cancer antibodies of the invention specifically bind to metastatic breast cancer or metastatic lung cancer proteins.
  • “specifically bind” herein is meant that the antibodies bind to the protein with a K d of at least about 0.1 mM, more usually at least about 1 ⁇ M, preferably at least about 0.1 ⁇ M or better, and most preferably, 0.01 ⁇ M or better. Selectivity of binding is also important.
  • the RNA expression levels of genes are determined for different cellular states in the metastatic breast cancer or metastatic lung cancer phenotype. Expression levels of genes in normal tissue (i.e., not undergoing metastatic breast cancer or metastatic lung cancer) and in metastatic breast cancer or metastatic lung cancer tissue (and in some cases, for varying severities of metastatic breast cancer or metastatic lung cancer that relate to prognosis, as outlined below) are evaluated to provide expression profiles.
  • An expression profile of a particular cell state or point of development is essentially a "fingerprint" of the state. While two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is reflective of the state of the cell.
  • differential expression refers to qualitative or quantitative differences in the temporal and/or cellular gene expression patterns within and among cells and tissue.
  • a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, e.g., normal versus metastatic breast cancer or metastatic lung cancer tissue.
  • Genes may be turned on or turned off in a particular state, relative to another state thus permitting comparison of two or more states.
  • a qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard techniques. Some genes will be expressed in one state or cell type, but not in both.
  • the difference in expression may be quantitative, e.g., in that expression is increased or decreased; i.e., gene expression is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript.
  • the degree to which expression differs need only be large enough to quantify via standard characterization techniques as outlined below, such as by use of GENECHIP ® (DNA microarray) expression arrays from Affymetrix, Inc. (Santa Clara, CA), as described in Lockhart et al, Nature Biotechnology 14:1675-1680 (1996), hereby expressly incorporated by reference.
  • Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, northern analysis and RNase protection.
  • the change in expression i.e., upregulation or dowmegulation
  • the change in expression is typically at least about 50%, more preferably at least about 100%), more preferably at least about 150%), more preferably at least about 200%, with from 300 to at least 1000%) being especially preferred.
  • Evaluation may be at the gene transcript, or the protein level.
  • the amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, e.g., with antibodies to the metastatic breast cancer or metastatic lung cancer protein and standard immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc.
  • Proteins corresponding to metastatic breast cancer or metastatic lung cancer genes i.e., those identified as being important in a metastatic breast cancer or metastatic lung cancer phenotype, can be evaluated in a metastatic breast cancer or metastatic lung cancer diagnostic test.
  • gene expression monitoring is performed simultaneously on a number of genes.
  • the metastatic breast cancer or metastatic lung cancer nucleic acid probes may be attached to biochips as outlined herein for the detection and quantification of metastatic breast cancer or metastatic lung cancer sequences in a particular cell.
  • the assays are further described below in the example. PCR techniques can be used to provide greater sensitivity. Multiple protein expression monitoring can be performed as well. Similarly, these assays may be performed on an individual basis as well.
  • nucleic acids encoding the metastatic breast cancer or metastatic lung cancer protein are detected.
  • DNA or RNA encoding the metastatic breast cancer or metastatic lung cancer protein may be detected, of particular interest are methods wherein an mRNA encoding a metastatic breast cancer or metastatic lung cancer protein is detected.
  • Probes to detect mRNA can be a nucleotide/deoxynucleotide probe that is complementary to and hybridizes with the mRNA and includes, but is not limited to, oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein.
  • the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample. Following washing to remove the non-specifically bound probe, the label is detected.
  • detection of the mRNA is performed in situ. In this method permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA. Following washing to remove the non-specifically bound probe, the label is detected.
  • RNA probe for example a digoxygenin labeled riboprobe (RNA probe) that is complementary to the mRNA encoding a metastatic breast cancer or metastatic lung cancer protein is detected by binding the digoxygenin with an anti-digoxygenin secondary antibody and developed with nitro blue tetrazolium and 5-bromo-4-chloro-3-indoyl phosphate.
  • various proteins from the three classes of proteins as described herein are used in diagnostic assays.
  • the metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing metastatic breast cancer or metastatic lung cancer sequences are used in diagnostic assays. This can be performed on an individual gene or corresponding polypeptide level.
  • the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes and/or corresponding polypeptides.
  • metastatic breast cancer or metastatic lung cancer proteins including intracellular, transmembrane or secreted proteins, find use as markers of metastatic breast cancer or metastatic lung cancer.
  • Detection of these proteins in putative metastatic breast cancer or metastatic lung cancer tissue allows for detection or diagnosis of metastatic breast cancer or metastatic lung cancer.
  • antibodies are used to detect metastatic breast cancer or metastatic lung cancer proteins.
  • a preferred method separates proteins from a sample by electrophoresis on a gel (typically a denaturing and reducing protein gel, but may be another type of gel, including isoelectric focusing gels and the like).
  • the metastatic breast cancer or metastatic lung cancer protein is detected, e.g., by immunoblotting with antibodies raised against the metastatic breast cancer or metastatic lung cancer protein. Methods of immunoblotting are well known to those of ordinary skill in the art.
  • antibodies to the metastatic breast cancer or metastatic lung cancer protein find use in in situ imaging techniques, e.g., in histology (e.g., Methods in Cell Biology: Antibodies in Cell Biology, volume 37 (Asai, ed. 1993)).
  • cells are contacted with from one to many antibodies to the metastatic breast cancer or metastatic lung cancer protein(s).
  • the presence of the antibody or antibodies is detected.
  • the antibody is detected by incubating with a secondary antibody that contains a detectable label, e.g., multicolor fluorescence or confocal imaging.
  • the primary antibody to the metastatic breast cancer or metastatic lung cancer protein(s) contains a detectable label, e.g., an enzyme marker that can act on a substrate.
  • each one of multiple primary antibodies contains a distinct and detectable label. This method finds particular use in simultaneous screening for a plurality of metastatic breast cancer or metastatic lung cancer proteins. Many other histological imaging techniques are also provided by the invention.
  • the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths.
  • a fluorescence activated cell sorter FACS
  • FACS fluorescence activated cell sorter
  • antibodies find use in diagnosing metastatic breast cancer or metastatic lung cancer from blood, serum, plasma, stool, and other samples. Such samples, therefore, are useful as samples to be probed or tested for the presence of metastatic breast cancer or metastatic lung cancer proteins.
  • Antibodies can be used to detect a metastatic breast cancer or metastatic lung cancer protein by previously described immunoassay techniques including ELISA, immunoblotting (western blotting), immunoprecipitation, BIACORE technology and the like.
  • the presence of antibodies may indicate an immune response against an endogenous metastatic breast cancer or metastatic lung cancer protein or vaccine.
  • in situ hybridization of labeled metastatic breast cancer or metastatic lung cancer nucleic acid probes to tissue arrays is done. For example, arrays of tissue samples, including metastatic breast cancer or metastatic lung cancer tissue and/or normal tissue, are made, ht situ hybridization (see, e.g., Ausubel, supra) is then performed.
  • ht situ hybridization see, e.g., Ausubel, supra
  • the skilled artisan can make a diagnosis, a prognosis, or a prediction based on the findings. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis and molecular profiling of the condition of the cells may lead to distinctions between responsive or refractory conditions or may be predictive of outcomes.
  • metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing metastatic breast cancer or metastatic lung cancer sequences are used in prognosis assays.
  • gene expression profiles can be generated that correlate to metastatic breast cancer or metastatic lung cancer, in terms of long term prognosis. Again, this may be done on either a protein or gene level, with the use of genes being preferred.
  • metastatic breast cancer or metastatic lung cancer probes may be attached to biochips for the detection and quantification of metastatic breast cancer or metastatic lung cancer sequences in a tissue or patient. The assays proceed as outlined above for diagnosis. PCR method may provide more sensitive and accurate quantification.
  • members of the three classes of proteins as described herein are used in drug screening assays.
  • the metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing metastatic breast cancer or metastatic lung cancer sequences are used in drug screening assays or by evaluating the effect of drag candidates on a "gene expression profile" or expression profile of polypeptides.
  • the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent (e.g., Zlokarnik, et al, Science 279:84-8 (1998); Heid, Genome Res 6:986-94, 1996).
  • the metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified metastatic breast cancer or metastatic lung cancer proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the metastatic breast cancer or metastatic lung cancer phenotype or an identified physiological function of a metastatic breast cancer or metastatic lung cancer protein. As above, this can be done on an individual gene level or by evaluating the effect of drag candidates on a "gene expression profile".
  • the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, see Zlokamik, supra.
  • assays may be ran on an individual gene or protein level. That is, having identified a particular gene with altered regulation in metastatic breast cancer or metastatic lung cancer, test compounds can be screened for the ability to modulate gene expression or for binding to the metastatic breast cancer or metastatic lung cancer protein. "Modulation" thus includes an increase or a decrease in gene expression. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tissue undergoing metastatic breast cancer or metastatic lung cancer, with changes of at least 10%>, preferably 50%, more preferably 100-300%), and in some embodiments 300-1000% or greater.
  • a gene exhibits a 4-fold increase in metastatic breast cancer or metastatic lung cancer tissue compared to normal tissue, a decrease of about four-fold is often desired; similarly, a 10-fold decrease in metastatic breast cancer or metastatic lung cancer tissue compared to normal tissue often provides a target value of a 10- fold increase in expression to be induced by the test compound.
  • the amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the gene product itself can be monitored, e.g., through the use of antibodies to the metastatic breast cancer or metastatic lung cancer protein and standard immunoassays. Proteomics and separation techniques may also allow quantification of expression.
  • gene or protein expression monitoring of a number of entities i.e., an expression profile
  • Such profiles will typically involve a plurality of those entities described herein.
  • the metastatic breast cancer or metastatic lung cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of metastatic breast cancer or metastatic lung cancer sequences in a particular cell.
  • PCR may be used.
  • a series e.g., of microtiter plate, may be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well.
  • Expression monitoring can be performed to identify compounds that modify the expression of one or more metastatic breast cancer or metastatic lung cancer-associated sequences, e.g., a polynucleotide sequence set out in Tables 1-12.
  • a test compound is added to the cells prior to analysis.
  • screens are also provided to identify agents that modulate metastatic breast cancer or metastatic lung cancer, modulate metastatic breast cancer or metastatic lung cancer proteins, bind to a metastatic breast cancer or metastatic lung cancer protein, or interfere with the binding of a metastatic breast cancer or metastatic lung cancer protein and an antibody, substrate, or other binding partner.
  • test compound or “drug candidate” or “modulator” or grammatical equivalents as used herein describes any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the metastatic breast cancer or metastatic lung cancer phenotype or the expression of a metastatic breast cancer or metastatic lung cancer sequence, e.g., a nucleic acid or protein sequence.
  • modulators alter expression profiles of nucleic acids or proteins provided herein.
  • the modulator suppresses a metastatic breast cancer or metastatic lung cancer phenotype, e.g., to a normal tissue fingerprint.
  • a modulator induces a metastatic breast cancer or metastatic lung cancer phenotype.
  • a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations.
  • one of these concentrations serves as a negative control, i.e., at zero concentration or below the level of detection.
  • a modulator will neutralize the effect of a metastatic breast cancer or metastatic lung cancer protein.
  • neutralize is meant that activity of a protein and the consequent effect on the cell is inhibited or blocked.
  • combinatorial libraries of potential modulators will be screened for an ability to bind to a metastatic breast cancer or metastatic lung cancer polypeptide or to modulate activity.
  • new chemical entities with useful properties are generated by identifying a chemical compound (called a "lead compound") with some desirable property or activity, e.g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds.
  • HTS high throughput screening
  • high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such "combinatorial chemical libraries” are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds” or can themselves be used as potential or actual therapeutics.
  • a combinatorial chemical library is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical "building blocks" such as reagents.
  • a linear combinatorial chemical library such as a polypeptide (e.g., mutein) library, is formed by combining a set of chemical building blocks called amino acids in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound). Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks (Gallop et al, J. Med. Chem. 37(9):1233-1251 (1994)). Preparation and screening of combinatorial chemical libraries is well known to those of skill in the art.
  • Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Patent No. 5,010,175, Furka, Pept. Prot. Res. 37:487-493 (1991), Houghton et al, Nature, 354:84-88 (1991)), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio-oligomers (PCT Publication WO 92/00091), benzodiazepines (U.S. Pat. No.
  • Patent 5,539,083, which is hereby incorporated by reference herein antibody libraries (see, e.g., Vaughn et al, Nature Biotechnology 14(3):309-314 (1996), and PCT/US96/10287), carbohydrate libraries (see, e.g., Liang et al, Science 274:1520-1522 (1996), and U.S. Patent No. 5,593,853, which is hereby incorporated by reference herein), and small organic molecule libraries (see, e.g., benzodiazepines, Baum, C&EN, Jan 18, page 33 (1993); isoprenoids, U.S. Patent No.
  • a number of well known robotic systems have also been developed for solution phase chemistries. These systems include automated workstations like the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate II, Zymark Corporation, Hopkinton, Mass.; Orca, Hewlett-Packard, Palo Alto, Calif), which mimic the manual synthetic operations performed by a chemist.
  • the above devices, with appropriate modification, are suitable for use with the present invention.
  • numerous combinatorial libraries are themselves commercially available (see, e.g., ComGenex, Princeton, N.J.; Asinex, Moscow, RU; Tripos, Inc., St. Louis, MO; ChemStar, Ltd, Moscow, RU; 3D Pharmaceuticals, Exton, PA; Martek Biosciences, Columbia, MD, etc.).
  • the assays to identify modulators are amenable to high throughput screening. Preferred assays thus detect modulation of metastatic breast cancer or metastatic lung cancer gene transcription, polypeptide expression, and polypeptide activity.
  • high throughput screening systems are commercially available (see, e.g., Zymark Corp., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman Instruments, Inc. Fullerton, CA; Precision Systems, Inc., Natick, MA, etc.). These systems typically automate procedures, including sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the assay.
  • These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems.
  • Zymark Corp. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.
  • modulators are proteins, often naturally occurring proteins or fragments of naturally occurring proteins.
  • cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts may be used.
  • libraries of proteins may be made for screening in the methods of the invention.
  • Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred.
  • Particularly useful test compound will be directed to the class of proteins to which the target belongs, e.g., substrates for enzymes or ligands and receptors.
  • modulators are peptides of from about 5 to about 30 amino acids, with from about 5 to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred.
  • the peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or "biased” random peptides.
  • randomized or grammatical equivalents herein is meant that the nucleic acid or peptide consists of essentially random sequences of nucleotides and amino acids, respectively. Since these random peptides (or nucleic acids, discussed below) are often chemically synthesized, they may incorporate any nucleotide or amino acid at any position.
  • the synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents.
  • the library is fully randomized, with no sequence preferences or constants at any position.
  • the library is biased. That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities.
  • the nucleotides or amino acid residues are randomized within a defined class, e.g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc.
  • a defined class e.g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc.
  • Modulators of metastatic breast cancer or metastatic lung cancer can also be nucleic acids, as defined above.
  • nucleic acid modulating agents may be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. Digests of procaryotic or eucaryotic genomes may be used as is outlined above for proteins.
  • the candidate compounds are organic chemical moieties, a wide variety of which are available in the literature.
  • the sample containing a target sequence is analyzed.
  • the target sequence is prepared using known techniques.
  • the sample may be treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate.
  • an in vitro transcription with labels covalently attached to the nucleotides is performed.
  • the nucleic acids are labeled with biotin-FITC or PE, or with Cy-3 or Cy-5.
  • the target sequence is labeled with, e.g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe.
  • the label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected.
  • the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme.
  • the label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin.
  • the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis.
  • Nucleic acid assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes, as is generally outlined in U.S. Patent Nos. 5,681,702, 5,597,909, 5,545,730, 5,594,117, 5,591,584, 5,571,670, 5,580,731, 5,571,670, 5,591,584, 5,624,802, 5,635,352, 5,594,118, 5,359,100, 5,124,246 and 5,681,697, all of which are hereby incorporated by reference herein.
  • the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.
  • hybridization conditions may be used in the present invention, including high, moderate and low stringency conditions as outlined above.
  • the assays are generally run under stringency conditions which allow formation of the label probe hybridization complex only in the presence of target.
  • Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration, pH, organic solvent concentration, etc.
  • the reactions outlined herein may be accomplished in a variety of ways. Components of the reaction may be added simultaneously, or sequentially, in different orders, with preferred embodiments outlined below.
  • the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g., albumin, detergents, etc. which may be used to facilitate optimal hybridization and detection, and/or reduce nonspecific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target.
  • the assay data are analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.
  • Screens are performed to identify modulators of the metastatic breast cancer or metastatic lung cancer phenotype.
  • screening is performed to identify modulators that can induce or suppress a particular expression profile, thus preferably generating the associated phenotype.
  • screens can be performed to identify modulators that alter expression of individual genes.
  • screening is performed to identify modulators that alter a biological function of the expression product of a differentially expressed gene. Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product, or evaluate genetic polymorphisms. Genes can be screened for those that are induced in response to a candidate agent.
  • a screen as described above can be performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated metastatic breast cancer or metastatic lung cancer tissue reveals genes that are not expressed in normal tissue or metastatic breast cancer or metastatic lung cancer tissue, but are expressed in agent treated tissue.
  • agent-specific sequences can be identified and used by methods described herein for metastatic breast cancer or metastatic lung cancer genes or proteins. In particular these sequences and the proteins they encode find use in marking or identifying agent treated cells.
  • a test compound is administered to a population of , metastatic breast cancer or metastatic lung cancer cells, that have an associated metastatic breast cancer or metastatic lung cancer expression profile.
  • administration or “contacting” herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface.
  • nucleic acid encoding a proteinaceous candidate agent may be put into a viral construct such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is accomplished, e.g., PCT US97/01019.
  • a viral construct such as an adenoviral or retroviral construct
  • Regulatable gene therapy systems can also be used.
  • the test compound Once the test compound has been administered to the cells, the cells can be washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.
  • metastatic breast cancer or metastatic lung cancer tissue may be screened for agents that modulate, e.g., induce or suppress the metastatic breast cancer or metastatic lung cancer phenotype.
  • a change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on metastatic breast cancer or metastatic lung cancer activity.
  • Measure of metastatic breast cancer or metastatic lung cancer polypeptide activity, or of metastatic breast cancer or metastatic lung cancer or the metastatic breast cancer or metastatic lung cancer phenotype can be performed using a variety of assays.
  • the effects of the test compounds upon the function of the metastatic polypeptides can be measured by examining parameters described above.
  • a suitable physiological change that affects activity can be used to assess the influence of a test compound on the polypeptides of this invention.
  • metastatic breast cancer or metastatic lung cancer associated with tumors, tumor growth, tumor metastasis, neovascularization, hormone release, transcriptional changes to both known and uncharacterized genetic markers (e.g., northern blots), changes in cell metabolism such as cell growth or pH changes, and changes in intracellular second messengers such as cGMP.
  • mammalian metastatic breast cancer or metastatic lung cancer polypeptide is typically used, e.g., mouse, preferably human.
  • Assays to identify compounds with modulating activity can be performed in vitro.
  • a metastatic breast cancer or metastatic lung cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e.g., from 0.5 to 48 hours.
  • the metastatic breast cancer or metastatic lung cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA.
  • the level of protein is measured using immunoassays such as western blotting, ELISA and the like with an antibody that selectively binds to the metastatic breast cancer or metastatic lung cancer polypeptide or a fragment thereof.
  • amplification e.g., using PCR, LCR, or hybridization assays, e.g., northern hybridization, RNAse protection, dot blotting, are prefened.
  • the level of protein or mRNA is detected using directly or indirectly labeled detection agents, e.g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein.
  • a reporter gene system can be devised using the metastatic breast cancer or metastatic lung cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or /3-gal.
  • the reporter construct is typically transfected into a cell. After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques known to those of skill in the art.
  • screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself can be done.
  • metastatic breast cancer or metastatic lung cancer proteins The gene products of differentially expressed genes are sometimes referred to herein as "metastatic breast cancer or metastatic lung cancer proteins.”
  • the metastatic breast cancer or metastatic lung cancer protem may be a fragment, or alternatively, be the full length protein to a fragment shown herein.
  • screening for modulators of expression of specific genes is performed. Typically, the expression of only one or a few genes are evaluated.
  • screens are designed to first find compounds that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity. Moreover, once initial candidate compounds are identified, variants can be further screened to better evaluate stracture activity relationships.
  • binding assays are done.
  • purified or isolated gene product is used; that is, the gene products of one or more differentially expressed nucleic acids are made.
  • antibodies are generated to the protein gene products, and standard immunoassays are ran to determine the amount of protein present.
  • cells comprising the metastatic breast cancer or metastatic lung cancer proteins can be used in the assays.
  • the methods comprise combining a metastatic breast cancer or metastatic lung cancer protein and a candidate compound, and determining the binding of the compound to the metastatic breast cancer or metastatic lung cancer protein.
  • Preferred embodiments utilize the human metastatic breast cancer or metastatic lung cancer protein, although other mammalian proteins may also be used, e.g., for the development of animal models of human disease.
  • variant or derivative metastatic breast cancer or metastatic lung cancer proteins may be used.
  • the metastatic breast cancer or metastatic lung cancer protein or the candidate agent is non-diffusably bound to an insoluble support having isolated sample receiving areas (e.g., a microtiter plate, an anay, etc.).
  • the insoluble supports may be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening.
  • the surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports include microtiter plates, anays, membranes and beads. These are typically made of glass, plastic (e.g., polystyrene), polysaccharides, nylon or nitrocellulose, TEFLON ® , etc.
  • Microtiter plates and anays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples.
  • the particular manner of binding of the composition is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable.
  • Prefened methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protem is bound to the support), direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety.
  • BSA bovine serum albumin
  • the metastatic breast cancer or metastatic lung cancer protein is bound to the support, and a test compound is added to the assay.
  • the candidate agent is bound to the support and the metastatic breast cancer or metastatic lung cancer protein is added.
  • Novel binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like.
  • the determination of the binding of the test modulating compound to the metastatic breast cancer or metastatic lung cancer protein may be done in a number of ways.
  • the compound is labeled, and binding determined directly, e.g., by attaching all or a portion of the metastatic breast cancer or metastatic lung cancer protein to a solid support, adding a labeled candidate agent (e.g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support.
  • a labeled candidate agent e.g., a fluorescent label
  • washing off excess reagent e.g., a fluorescent label
  • only one of the components is labeled, e.g., the proteins (or proteinaceous candidate compounds) can be labeled.
  • more than one component can be labeled with different labels, e.g., 125 I for the proteins and a fluorophor for the compound.
  • Proximity reagents e.g., quenching or energy transfer reagents are also useful.
  • the binding of the test compound is determined by competitive binding assay.
  • the competitor is a binding moiety known to bind to the target molecule (i.e., a metastatic breast cancer or metastatic lung cancer protein), such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding between the compound and the binding moiety, with the binding moiety displacing the compound.
  • the test compound is labeled. Either the compound, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present. Incubations may be performed at a temperature which facilitates optimal activity, typically between 4 and 40°C. Incubation periods are typically optimized, e.g., to facilitate rapid high throughput screening. Typically between 0.1 and 1 hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.
  • the competitor is added first, followed by the test compound.
  • Displacement of the competitor is an indication that the test compound is binding to the metastatic breast cancer or metastatic lung cancer protein and thus is capable of binding to, and potentially modulating, the activity of the metastatic breast cancer or metastatic lung cancer protein.
  • either component can be labeled.
  • the presence of label in the wash solution indicates displacement by the agent.
  • the test compound is labeled, the presence of the label on the support indicates displacement.
  • the test compound is added first, with incubation and washing, followed by the competitor.
  • the absence of binding by the competitor may indicate that the test compound is bound to the metastatic breast cancer or metastatic lung cancer protein with a higher affinity.
  • the presence of the label on the support, coupled with a lack of competitor binding may indicate that the test compound is capable of binding to the metastatic breast cancer or metastatic lung cancer protein.
  • the methods comprise differential screening to identity agents that are capable of modulating the activity of the metastatic breast cancer or metastatic lung cancer proteins.
  • the methods comprise combining a metastatic breast cancer or metastatic lung cancer protein and a competitor in a first sample.
  • a second sample comprises a test compound, a metastatic breast cancer or metastatic lung cancer protein, and a competitor.
  • the binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the metastatic breast cancer or metastatic lung cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the metastatic breast cancer or metastatic lung cancer protein.
  • differential screening is used to identify drag candidates that bind to the native metastatic breast cancer or metastatic lung cancer protem, but cannot bind to modified metastatic breast cancer or metastatic lung cancer proteins.
  • the stracture of the metastatic breast cancer or metastatic lung cancer protein may be modeled, and used in rational drag design to synthesize agents that interact with that site.
  • Drag candidates that affect the activity of a metastatic breast cancer or metastatic lung cancer protein are also identified by screening drags for the ability to either enhance or reduce the activity of the protein.
  • Positive controls and negative controls may be used in the assays.
  • control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein. Following incubation, samples are washed free of non-specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.
  • reagents may be included in the screening assays. These include reagents like salts, neutral proteins, e.g., albumin, detergents, etc. which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components may be added in an order that provides for the requisite binding. In a prefened embodiment, the invention provides methods for screening for a compound capable of modulating the activity of a metastatic breast cancer or metastatic lung cancer protein.
  • the methods comprise adding a test compound, as defined above, to a cell comprising metastatic breast cancer or metastatic lung cancer proteins.
  • Prefened cell types include almost any cell.
  • the cells contain a recombinant nucleic acid that encodes a metastatic breast cancer or metastatic lung cancer protein.
  • a library of candidate agents are tested on a plurality of cells.
  • the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e.g., hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i.e. cell-cell contacts).
  • physiological signals e.g., hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i.e. cell-cell contacts).
  • the determinations are determined at different stages of the cell cycle process.
  • a method of inhibiting metastatic breast cancer or metastatic lung cancer cell division comprises administration of a metastatic breast cancer or metastatic lung cancer inhibitor.
  • a method of inhibiting metastatic breast cancer or metastatic lung cancer is provided.
  • the method comprises administration of a metastatic breast cancer or metastatic lung cancer inhibitor.
  • methods of treating cells or individuals with metastatic breast cancer or metastatic lung cancer are provided.
  • the method comprises administration of a metastatic breast cancer or metastatic lung cancer inhibitor.
  • Soft agar growth or colony formation in suspension Normal cells require a solid substrate to attach and grow. When the cells are transformed, they lose this phenotype and grow detached from the substrate. For example, transformed cells can grow in sti ⁇ ed suspension culture or suspended in semi-solid media, such as semi-solid or soft agar. The transformed cells, when transfected with tumor suppressor genes, regenerate normal phenotype and require a solid substrate to attach and grow. Soft agar growth or colony formation in suspension assays can be used to identify modulators of metastatic breast cancer or metastatic lung cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation. A therapeutic compound would reduce or eliminate the host cells' ability to grow in sti ⁇ ed suspension culture or suspended in semi-solid media, such as semi-solid or soft.
  • labeling index with ( 3 H)-thymidine at saturation density is a prefened method of measuring density limitation of growth.
  • Transformed host cells are transfected with a metastatic breast cancer or metastatic lung cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions.
  • the percentage of cells labeling with ( 3 H)-thymidine is determined autoradiographically. See, Freshney (1994), supra.
  • Tumor specific markers levels Tumor cells release an increased amount of certain factors (hereinafter "tumor specific markers") than their normal counterparts.
  • plasminogen activator PA is released from human glioma at a higher level than from normal brain cells (see, e.g.,
  • Tumor angiogenesis factor TAF is released at a higher level in tumor cells than their normal counterparts. See, e.g., Folkman, Angiogenesis and Cancer, Sem Cancer Biol. (1992)). Various techniques which measure the release of these factors are described in
  • Invasiveness into Matrigel The degree of invasiveness into Matrigel or some other extracellular matrix constituent can be used as an assay to identify compounds that modulate metastatic breast cancer or metastatic lung cancer-associated sequences.
  • Tumor cells exhibit a good co ⁇ elation between malignancy and invasiveness of cells into Matrigel or some other extracellular matrix constituent.
  • tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells. Techniques described in Freshney (1994), supra, can be used. Briefly, the level of invasion of host cells can be measured by using filters coated with Matrigel or some other extracellular matrix constituent.
  • Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by number of cells and distance moved, or by prelabeling the cells with 125 I and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e.g., Freshney (1984), supra.
  • Knock-out fransgenic mice can be made, in which the metastatic breast cancer or metastatic lung cancer gene is disrupted or in which a metastatic breast cancer or metastatic lung cancer gene is inserted.
  • Knock-out fransgenic mice can be made by insertion of a marker gene or other heterologous gene into the endogenous metastatic breast cancer or metastatic lung cancer gene site in the mouse genome via homologous recombination.
  • mice can also be made by substituting the endogenous metastatic breast cancer or metastatic lung cancer gene with a mutated version of the metastatic breast cancer or metastatic lung cancer gene, or by mutating the endogenous metastatic breast cancer or metastatic lung cancer gene, e.g., by exposure to carcinogens.
  • a DNA construct is introduced into the nuclei of embryonic stem cells. Cells containing the newly engineered genetic lesion are injected into a host mouse embryo, which is re-implanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells partially derived from the mutant cell line.
  • Chimeric targeted mice can be derived according to Hogan et al. , Manipulating the Mouse Embryo: A Laboratory Manual, Cold Spring Harbor Laboratory (1988) and Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, Robertson, ed., IRL Press, Washington, D.C., (1987).
  • various immune-suppressed or immune-deficient host animals can be used.
  • genetically athymic "nude" mouse see, e.g., Giovanella et al, J. Natl Cancer Inst. 52:921 (1974)
  • SCID mouse a SCID mouse
  • a thymectomized mouse a thymectomized mouse
  • an inadiated mouse see, e.g., Bradley et al, Br. J. Cancer 38:263 (1978); Selby et al, Br. J. Cancer 41:52 (1980)
  • Transplantable tumor cells typically about 10 6 cells
  • injected into isogenic hosts will produce invasive tumors in a high proportions of cases, while normal cells of similar origin will not.
  • tumor growth is measured (e.g., by volume or by its two largest dimensions) and compared to the control. Tumors that have statistically significant reduction (using, e.g., Student's T test) are said to have inhibited growth.
  • human tumor cells expressing the genes of the invention may be injected into immune compromised animals. Growth of these tumors, or xenografts, is compared to growth of similar human tumor cell that do not express the genes of the invention. These animals may also be used to binding assays and efficacy studies for therapeutic compounds that modulate metastatic breast cancer or metastatic lung cancer, such as antibodies or small molecules.
  • the activity of a metastatic breast cancer or metastatic lung cancer-associated protein is downregulated, or entirely inhibited, by the use of antisense polynucleotide, i.e., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a metastatic breast cancer or metastatic lung cancer protein mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of the mRNA.
  • antisense polynucleotide i.e., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a metastatic breast cancer or metastatic lung cancer protein mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/
  • antisense polynucleotides can comprise naturally- occurring nucleotides, or synthetic species formed from naturally-occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter- sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species which are known for use in the art. Analogs are comprehended by this invention so long as they function effectively to hybridize with the metastatic breast cancer or metastatic lung cancer protein mRNA. See, e.g., Isis Pharmaceuticals, Carlsbad, CA; Sequitor, Inc., Natick, MA.
  • antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems (Norwalk, CT). The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known to those of skill in the art.
  • Antisense molecules as used herein include antisense or sense oligonucleotides.
  • Sense oligonucleotides can, e.g., be employed to block transcription by binding to the anti- sense strand.
  • the antisense and sense oligonucleotide comprise a single-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for metastatic breast cancer or metastatic lung cancer molecules.
  • a prefened antisense molecule is for a metastatic breast cancer or metastatic lung cancer sequence selected from those listed in Tables 1 A-12C, or for a ligand or activator thereof.
  • Antisense or sense oligonucleotides comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides.
  • the ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, e.g., Stein & Cohen (Cancer Res. 48:2659 (1988 and van der Krol et al. (BioTechniques 6:958 (1988)).
  • Ribozymes In addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of metastatic breast cancer or metastatic lung cancer-associated nucleotide sequences.
  • a ribozyme is an RNA molecule that catalytically cleaves other RNA molecules.
  • Different kinds of ribozymes have been described, including group I ribozymes, hammerhead ribozymes, hairpin ribozymes, RNase P, and axhead ribozymes (see, e.g., Castanotto et al, Adv. in Pharmacology 25: 289-317 (1994) for a general review of the properties of different ribozymes).
  • hairpin ribozymes are described, e.g., in Hampel et al, Nucl Acids Res. 18:299-304 (1990); European Patent Publication No. 0 360 257; U.S. Patent No. 5,254,678, which is hereby incorporated by reference herein..
  • Methods of preparing are well known to those of skill in the art (see, e.g., WO 94/26877; Ojwang et al, Proc. Natl. Acad. Sci. USA 90:6340-6344 (1993); Yamada et al, Human Gene Therapy 1:39-45 (1994); Leavitt et al, Proc. Natl. Acad. Sci. USA 92:699-703 (1995); Leavitt et al, Human Gene Therapy 5:1151-120 (1994); and Yamada et al, Virology 205: 121-126 (1994)).
  • Polynucleotide modulators of metastatic breast cancer or metastatic lung cancer may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753.
  • Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors.
  • conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its conesponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell.
  • a polynucleotide modulator of metastatic breast cancer or metastatic lung cancer may be introduced into a cell containing the target nucleic acid sequence, e.g., by formation of an polynucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.
  • methods of modulating metastatic breast cancer or metastatic lung cancer in cells or organisms comprise administering to a cell an anti-metastatic breast cancer or metastatic lung cancer antibody that reduces or eliminates the biological activity of an endogenous metastatic breast cancer or metastatic lung cancer protein.
  • the methods comprise administering to a cell or organism a recombinant nucleic acid encoding a metastatic breast cancer or metastatic lung cancer protem. This may be accomplished in any number of ways.
  • a prefened embodiment e.g., when the metastatic breast cancer or metastatic lung cancer sequence is down-regulated in metastatic breast cancer or metastatic lung cancer, such state may be reversed by increasing the amount of metastatic breast cancer or metastatic lung cancer gene product in the cell.
  • This can be accomplished, e.g., by overexpressing the endogenous metastatic breast cancer or metastatic lung cancer gene or administering a gene encoding the metastatic breast cancer or metastatic lung cancer sequence, using known gene- therapy techniques.
  • the gene therapy techniques include the incorporation of the exogenous gene using enhanced homologous recombination (EHR), e.g., as described in PCT/US93/03868, hereby incorporated by reference in its entirety.
  • EHR enhanced homologous recombination
  • metastatic breast cancer or metastatic lung cancer proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to metastatic breast cancer or metastatic lung cancer proteins.
  • the metastatic breast cancer or metastatic lung cancer proteins can be coupled, using standard technology, to affinity chromatography columns. These columns may then be used to purify metastatic breast cancer or metastatic lung cancer antibodies useful for production, diagnostic, or therapeutic purposes.
  • the antibodies are generated to epitopes unique to a metastatic breast cancer or metastatic lung cancer protein; that is, the antibodies show little or no cross-reactivity to other proteins.
  • the metastatic breast cancer or metastatic lung cancer antibodies may be coupled to standard affinity chromatography columns and used to purify metastatic breast cancer or metastatic lung cancer proteins.
  • the antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the metastatic breast cancer or metastatic lung cancer protein.
  • metastatic breast cancer or metastatic lung cancer sequences is conelated with metastatic breast cancer or metastatic lung cancer. Accordingly, disorders based on mutant or variant metastatic breast cancer or metastatic lung cancer genes may be determined.
  • the invention provides methods for identifying cells containing variant metastatic breast cancer or metastatic lung cancer genes, e.g., determining all or part of the sequence of at least one endogenous metastatic breast cancer or metastatic lung cancer genes in a cell. This may be accomplished using any number of sequencing techniques.
  • the invention provides methods of identifying the metastatic breast cancer or metastatic lung cancer genotype of an individual, e.g., determining all or part of the sequence of at least one metastatic breast cancer or metastatic lung cancer gene of the individual. This is generally done in at least one tissue of the individual, and may include the evaluation of a number of tissues or different samples of the same tissue.
  • the method may include comparing the sequence of the sequenced metastatic breast cancer or metastatic lung cancer gene to a known metastatic breast cancer or metastatic lung cancer gene, i.e., a wild-type gene.
  • the sequence of all or part of the metastatic breast cancer or metastatic lung cancer gene can then be compared to the sequence of a known metastatic breast cancer or metastatic lung cancer gene to determine if any differences exist. This can be done using any number of known homology programs, such as Bestfit, etc.
  • the presence of a difference in the sequence between the metastatic breast cancer or metastatic lung cancer gene of the patient and the known metastatic breast cancer or metastatic lung cancer gene conelates with a disease state or a propensity for a disease state, as outlined herein.
  • the metastatic breast cancer or metastatic lung cancer genes are used as probes to detennine the number of copies of the metastatic breast cancer or metastatic lung cancer gene in the genome.
  • the metastatic breast cancer or metastatic lung cancer genes are used as probes to determine the chromosomal localization of the metastatic breast cancer or metastatic lung cancer genes.
  • Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the metastatic breast cancer or metastatic lung cancer gene locus.
  • a therapeutically effective dose of a metastatic breast cancer or metastatic lung cancer protein or modulator thereof is administered to a patient.
  • therapeutically effective dose herein is meant a dose that produces effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertamable by one skilled in the art using known techniques (e.g., Ansel et al, Pharmaceutical Dosage Forms and Drug Delivery; Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992), Dekker, ISBN 0824770846, 082476918X, 0824712692, 0824716981; Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); and Pickar, Dosage Calculations (1999)).
  • a "patient” for the purposes of the present invention includes both humans and other animals, particularly mammals. Thus the methods are applicable to both human therapy and veterinary applications.
  • the patient is a mammal, preferably a primate, and in the most prefened embodiment the patient is human.
  • metastatic breast cancer or metastatic lung cancer proteins and modulators thereof of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, infranasally, fransdermally, intraperitoneally, intramuscularly, intrapulmonary, vaginally, rectally, or intraocularly.
  • the metastatic breast cancer or metastatic lung cancer proteins and modulators may be directly applied as a solution or spray.
  • compositions of the present invention comprise a metastatic breast cancer or metastatic lung cancer protein in a form suitable for administration to a patient.
  • the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both acid and base addition salts.
  • “Pharmaceutically acceptable acid addition salt” refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyravic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like.
  • inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like
  • organic acids such as acetic acid, propionic acid, glycolic acid, pyravic acid,
  • “Pharmaceutically acceptable base addition salts” include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Particularly prefened are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
  • the pharmaceutical compositions may also include one or more of the following: carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, corn and other starches; binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol.
  • carrier proteins such as serum albumin
  • buffers such as buffers
  • fillers such as microcrystalline cellulose, lactose, corn and other starches
  • binding agents such as microcrystalline
  • the metastatic breast cancer or metastatic lung cancer modulators of the invention may need to be protected from excretion, hydrolisis, proteolytic digestion or modification, or detoxification by the liver.
  • protection is typically accomplished either by complexing the molecule(s) with a composition to render it resistant to acidic and enzymatic hydrolysis, or by packaging the molecule(s) in an appropriately resistant carrier, such as a liposome or a protection barrier or by modifying the molecular size, weight, and/or charge of the modulator.
  • an appropriately resistant carrier such as a liposome or a protection barrier
  • Means of protecting agents from digestion degradation, and excretion are well known in the art.
  • compositions for administration will commonly comprise a metastatic breast cancer or metastatic lung cancer protein modulator dissolved in a pharmaceutically acceptable carrier, preferably an aqueous carrier.
  • a pharmaceutically acceptable carrier preferably an aqueous carrier.
  • aqueous carriers can be used, e.g., buffered saline and the like. These solutions are sterile and generally free of undesirable matter.
  • These compositions may be sterilized by conventional, well known sterilization techniques.
  • the compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like.
  • concentration of active agent in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight and the like in accordance with the particular mode of administration selected and the patient's needs (e.g., Remington 's Pharmaceutical Science (15th ed., 1980) and Goodman & Gillman, 77ze Pharmacologial Basis ofTlierapeutics (Hardman et al., eds., 1996)).
  • a typical pharmaceutical composition for intravenous administration would be about 0.1 to 10 mg per patient per day.
  • Dosages from 0.1 up to about 100 mg per patient per day may be used, particularly when the drug is administered to a secluded site and not into the blood stream, such as into a body cavity or into a lumen of an organ. Substantially higher dosages are possible in topical administration. Actual methods for preparing parenterally administrable compositions will be known or apparent to those skilled in the art, e.g.,
  • compositions containing modulators of metastatic breast cancer or metastatic lung cancer proteins can be administered for therapeutic or prophylactic treatments.
  • compositions are administered to a patient suffering from a disease (e.g., a cancer) in an amount sufficient to cure or at least partially anest the disease and its complications.
  • An amount adequate to accomplish this is defined as a "therapeutically effective dose.” Amounts effective for this use will depend upon the severity of the disease and the general state of the patient's health.
  • Single or multiple administrations of the compositions may be administered depending on the dosage and frequency as required and tolerated by the patient. In any event, the composition should provide a sufficient quantity of the agents of this invention to effectively treat the patient.
  • An amount of modulator that is capable of preventing or slowing the development of cancer in a mammal is refened to as a "prophylactically effective dose.”
  • the particular dose required for a prophylactic treatment will depend upon the medical condition and history of the mammal, the particular cancer being prevented, as well as other factors such as age, weight, gender, administration route, efficiency, etc.
  • Such prophylactic treatments may be used, e.g., in a mammal who has previously had cancer to prevent a recunence of the cancer, or in a mammal who is suspected of having a significant likelihood of developing cancer.
  • metastatic breast cancer or metastatic lung cancer protein-modulating compounds can be administered alone or in combination with additional metastatic breast cancer or metastatic lung cancer modulating compounds or with other therapeutic agent, e.g., other anti-cancer agents or treatments.
  • additional metastatic breast cancer or metastatic lung cancer modulating compounds or with other therapeutic agent e.g., other anti-cancer agents or treatments.
  • one or more nucleic acids e.g., polynucleotides comprising nucleic acid sequences set forth in Tables 1 A-12C, such as antisense polynucleotides or ribozymes, will be introduced into cells, in vitro or in vivo.
  • the present invention provides methods, reagents, vectors, and cells useful for expression of metastatic breast cancer or metastatic lung cancer-associated polypeptides and nucleic acids using in vitro (cell-free), ex vivo or in vivo (cell or organism-based) recombinant expression systems.
  • the particular procedure used to introduce the nucleic acids into a host cell for expression of a protein or nucleic acid is application specific. Many procedures for introducing foreign nucleotide sequences into host cells may be used.
  • metastatic breast cancer or metastatic lung cancer proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above.
  • metastatic breast cancer or metastatic lung cancer genes (including both the full-length sequence, partial sequences, or regulatory sequences of the metastatic breast cancer or metastatic lung cancer coding regions) can be administered in a gene therapy application.
  • These metastatic breast cancer or metastatic lung cancer genes can include antisense applications, either as gene therapy (i.e., for incorporation into the genome) or as antisense compositions, as will be appreciated by those in the art.
  • Metastatic breast cancer or metastatic lung cancer polypeptides and polynucleotides can also be administered as vaccine compositions to stimulate HTL, CTL and antibody responses.
  • vaccine compositions can include, e.g., lipidated peptides (see, e.g.,Vitiello, et al, J. Gin. Invest. 95:341 (1995)), peptide compositions encapsulated in poly(DL-lactide- co-glycolide) ("PLG”) microspheres (see, e.g., Eldridge, et al, Molec. Immunol.
  • Toxin-targeted delivery technologies also known as receptor mediated targeting, such as those of Avant Immunotherapeutics, Inc. (Needham, Massachusetts) may also be used.
  • Vaccine compositions often include adjuvants.
  • Many adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins.
  • adjuvants are commercially available as, e.g., Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline Beecham, Philadelphia, PA); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A.
  • Cytokines such as GM-CSF, interleukin-2, -7, -12, and other like growth factors, may also be used as adjuvants.
  • Vaccines can be administered as nucleic acid compositions wherein DNA or RNA encoding one or more of the polypeptides, or a fragment thereof, is administered to a patient.
  • This approach is described, for instance, in Wolff et. al, Science 247:1465 (1990) as well as U.S. Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98/04720, each of which is hereby incorporated by reference herein.; and in more detail below.
  • DNA-based delivery technologies include "naked DNA”, facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle- mediated (“gene gun”) or pressure-mediated delivery (see, e.g., U.S. Patent No. 5,922,687, which is hereby incorporated by reference herein.).
  • the peptides of the invention can be expressed by viral or bacterial vectors.
  • expression vectors include attenuated viral hosts, such as vaccinia or fowlpox. This approach involves the use of vaccinia virus, e.g., as a vector to express nucleotide sequences that encode metastatic breast cancer or metastatic lung cancer polypeptides or polypeptide fragments. Upon introduction into a host, the recombinant vaccinia virus expresses the immunogenic peptide, and thereby elicits an immune response.
  • Vaccinia vectors and methods useful in immunization protocols are described in, e.g., U.S. Patent No.
  • BCG Bacillus Calmette Guerin
  • BCG vectors are described in Stover et al, Nature 351:456-460 (1991).
  • adeno and adeno-associated virus vectors retroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like, will be apparent to those skilled in the art from the description herein (see, e.g., Shata et al, Mol Med Today 6:66-71 (2000); Shedlock et al, JLeukoc Biol 68:793-806 (2000); Hipp et al, In Vivo 14:571-85 (2000)).
  • Methods for the use of genes as DNA vaccines are well known, and include placing a metastatic breast cancer or metastatic lung cancer gene or portion of a metastatic breast cancer or metastatic lung cancer gene under the control of a regulatable promoter or a tissue- specific promoter for expression in a metastatic breast cancer or metastatic lung cancer patient.
  • the metastatic breast cancer or metastatic lung cancer gene used for DNA vaccines can encode full-length metastatic breast cancer or metastatic lung cancer proteins, but more preferably encodes portions of the metastatic breast cancer or metastatic lung cancer proteins including peptides derived from the metastatic breast cancer or metastatic lung cancer protein.
  • a patient is immunized with a DNA vaccine comprising a plurality of nucleotide sequences derived from a metastatic breast cancer or metastatic lung cancer gene.
  • a DNA vaccine comprising a plurality of nucleotide sequences derived from a metastatic breast cancer or metastatic lung cancer gene.
  • metastatic breast cancer or metastatic lung cancer-associated genes or sequence encoding subfragments of a metastatic breast cancer or metastatic lung cancer protein are introduced into expression vectors and tested for their immunogenicity in the context of Class I MHC and an ability to generate cytotoxic T cell responses. This procedure provides for production of cytotoxic T cell responses against cells which present antigen, including intracellular epitopes.
  • the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine.
  • adjuvant molecules include cytokines that increase the immunogenic response to the metastatic breast cancer or metastatic lung cancer polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are available.
  • metastatic breast cancer or metastatic lung cancer genes find use in generating animal models of metastatic breast cancer or metastatic lung cancer. When the metastatic breast cancer or metastatic lung cancer gene identified is repressed or diminished in metastatic tissue, gene therapy technology, e.g., wherein antisense RNA directed to the metastatic breast cancer or metastatic lung cancer gene will also diminish or repress expression of the gene.
  • Animal models of metastatic breast cancer or metastatic lung cancer find use in screening for modulators of a metastatic breast cancer or metastatic lung cancer-associated sequence or modulators of metastatic breast cancer or metastatic lung cancer.
  • fransgenic animal technology including gene knockout technology, e.g., as a result of homologous recombination with an appropriate gene targeting vector, will result in the absence or increased expression of the metastatic breast cancer or metastatic lung cancer protein.
  • tissue-specific expression or knockout of the metastatic breast cancer or metastatic lung cancer protein may be necessary. It is also possible that the metastatic breast cancer or metastatic lung cancer protein is overexpressed in metastatic breast cancer or metastatic lung cancer.
  • fransgenic animals can be generated that overexpress the metastatic breast cancer or metastatic lung cancer protein.
  • promoters of various strengths can be employed to express the fransgene.
  • the number of copies of the integrated fransgene can be determined and compared for a determination of the expression level of the fransgene. Animals generated by such methods find use as animal models of metastatic breast cancer or metastatic lung cancer and are additionally useful in screening for modulators to treat metastatic breast cancer or metastatic lung cancer.
  • kits are also provided by the invention.
  • such kits may include any or all of the following: assay reagents, buffers, metastatic breast cancer or metastatic lung cancer-specific nucleic acids or antibodies, hybridization probes and/or primers, antisense polynucleotides, ribozymes, dominant negative metastatic breast cancer or metastatic lung cancer polypeptides or polynucleotides, small molecules inhibitors of metastatic breast cancer or metastatic lung cancer-associated sequences etc.
  • a therapeutic product may include sterile saline or another pharmaceutically acceptable emulsion and suspension base.
  • kits may include instructional materials containing directions (i.e., protocols) for the practice of the methods of this invention.
  • instructional materials typically comprise written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this invention.
  • Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like.
  • Such media may include addresses to internet sites that provide such instructional materials.
  • kits for screening for modulators of metastatic breast cancer or metastatic lung cancer-associated sequences can be prepared from readily available materials and reagents.
  • such kits can comprise one or more of the following materials: a metastatic breast cancer or metastatic lung cancer- associated polypeptide or polynucleotide, reaction tubes, and instructions for testing metastatic breast cancer or metastatic lung cancer-associated activity.
  • the kit contains biologically active metastatic breast cancer or metastatic lung cancer protem.
  • kits and components can be prepared according to the present invention, depending upon the intended user of the kit and the particular needs of the user. Diagnosis would typically involve evaluation of a plurality of genes or products. The genes will be selected based on conelations with important parameters in disease which may be identified in historical or outcome data.
  • Table 1 A shows about 461 genes pregulated In breast metastases to the brain relative to normal breast tissues These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 2A shows about 445 genes Upregulated in breast metastases to the brain relative to normal body tissues These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 3A shows about 216 genes upregulated In breast metastases to the brain relative to p ⁇ mary breast tumors These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 4A shows about 350 genes downregulated In breast metastases to the brain relative to pnmary breast tumors These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 5A shows about 489 genes downregulated In breast metastases to the brain relative to normal breast tissue These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 6A shows about 1251 genes upregulated in lung metastases to the brain relative to normal lung tissues These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 7A shows about 381 genes upregulated In lung metastases to the brain relative to normal body tissues These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 8A shows about 330 genes upregulated In lung metastases to the brain relative to p ⁇ mary lung tumors These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 9A shows about 252 genes downregulated In lung metastases to the brain relative to pnmary lung tumors These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 10A shows about 289 genes downregulated in lung metastases to the brain relative to normal lung tissue These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 11 A shows about 1198 genes upregulated in breast and lung metastases to the brain relative to normal body tissues These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Table 12A shows about 2867 genes upregulated In breast and lung metastases to the brain relative to normal breast and lung tissues These genes were selected from 59680 probesets on the Eos/Affymet ⁇ x Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
  • Tables 1B-12C shows the accession numbers for those pkeys in Tables 1A-12A lacking unlgenelD's
  • Tables 1B-12C shows the accession numbers for those pkeys in Tables 1A-12A lacking unlgenelD's
  • Gene clusters were compiled using sequences denved from Ge ⁇ bank ESTs and mRNAs These sequences were clustered based on sequence simllanty using Cluste ⁇ ng and Alignment Tools (DoubleTwist, Oakland California) The Genbank accession numbers for sequences compnsing each cluster are listed in the Accession column
  • Tables 1C-12C shows genomic positioning for those pkeys lacking unlgene ID's and accession numbers in tables 1A-12A
  • genomic sequence source used for prediction Nucleotide locations of each predicted exon are also listed
  • RAIG1 retinoic acid Induced 3
  • HDGF hepatoma-de ⁇ ved growth factor
  • AI334881 AW075006 AW075181 AA464019 AW302733 AW075100 AW073433 AI802854 AI334909 AI802853 AI345036 AI348921 AI340734
  • AI307478 AI251289 AW302327 AW072520 AI312145 AW073656 AW072513 AW071289 AI307559 AA876186 T29587 AI307493 AI255068
  • AI252868 AI252839 AW074809 AI252926 AI252160 AI251662 AI251262 AI610913 AI270787 AI270156 AI252075 AW073469 AW072901
  • AI334733 AI054335 BE139260 AI054302
  • AI054060 AI054057 AI053722
  • AI289711 BE139228 AW470478 AW271039 AW302085 BE041872

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Abstract

Described herein are methods and compositions that can be used for diagnosis and treatment of metastatic cancer. Also described herein are methods that can be used to identify modulators of metastatic cancer.

Description

NOVEL METHODS OF DIAGNOSIS OF METASTATIC CANCER,
COMPOSITIONS AND METHODS OF SCREENING FOR
MODULATORS OF METASTATIC CANCER
FIELD OF THE INVENTION
The invention relates to the identification of nucleic acids and proteins identified by expression profiles, and nucleic acids, products, and antibodies thereto that are involved in metastatic cancer; and to the use of such expression profiles and compositions in diagnosis and therapy of metastatic cancer. The invention further relates to methods for identifying and using agents and/or targets that inhibit metastatic cancer.
BACKGROUND OF THE INVENTION Metastatic disease can be viewed as two simultaneously occurring diseases; a disease at a primary site, and a related disease at a secondary location distant from the primary site. Each disease may have different mortality rates, for example in cases of metastatic breast or lung cancer to the brain. In such cases untreated brain metastases are rapidly fatal, while primary breast or lung cancer may actually be cureable.
Unfortunately, many cancers metastasize. While there are many variables that determine where metastatic tumors grow, often, the metastatic location is the nearest cluster of small blood vessels found by the circulating cancer cells. Thus, lung cancer commonly metastasizes to the brain; colon cancer commonly metastasizes to the liver. Alternatively, the cancer may have a preferred site of metastasis. For example, the brain is a preferred site for melanoma and small cell lung cancer. A metastasis of a metastasis may develop as well. For example, a colon cancer may metastasize to the liver, which in rum may metastasize to the lung, which may in turn metastasize to the brain.
Without wishing to be bound by theory, it is believed that metastasis occurs when cancer cells from the primary site break away and enter the body's circulatory system through the blood stream, lymph system, or spinal fluid and travel to distant locations. Although cancer metastasis may occur in nearly any organ, brain metastases are one of the most common sites of systemic spread from solid tumors, with an annual incidence of over 100,000 cases. Indeed, metastatic brain tumors occur in about one-fourth of all cancers that metastasize, and primary and metastatic brain tumors kill 15,000 people each year. The most common primary tumors that metastasize to the brain are lung, breast, melanoma, and colon, however almost any cancer has this potential. lthough almost 1 in 4 patients with cancer will develop tumors that spread to the central nervous system (CNS) cancer can metastasize to almost any organ.
Classification of metastatic tumors depends on the tissue type from which they are derived. Unfortunately, it is often difficult or impossible to determine the location of the primary cancer and this can unnecessarily complicate diagnosis and treatment of the metastatic cancer. In addition early diagnosis of metastatic cancer can greatly improve the prognostic outlook for a cancer patient. Often metastatic burden, rather than the primary cancer, is what ultimately kills a patient.
Thus need exists for an efficient and effective method for the identification of metastatic tumor origins, as well as methods for diagnosis, prognosis and treatment of metastatic cancer. The development of successful therapeutic modalities is however, unlikely to follow the conventional approaches of surgery, radiation and cytotoxic chemotherapy. Rather, the best hope lies in the rapidly expanding field of molecular medicine.
Accordingly, provided herein are molecular targets for therapeutic intervention in metastatic breast and lung cancer. Additionally, provided herein are methods that can be used in diagnosis and prognosis of metastatic breast and lung cancer. Further provided are methods that can be used to screen candidate bioactive agents for the ability to modulate metastatic cancer including metastatic brain tumors.
SUMMARY OF THE INVENTION The present invention therefore provides nucleotide sequences of genes that are up- and down-regulated in metastatic breast or metastatic lung cancer cells. Such genes and the proteins they encode are useful for diagnostic and prognostic purposes, and also as targets for screening for therapeutic compounds that modulate metastatic breast or lung cancer, such as antibodies. The methods of detecting nucleic acids of the invention or their encoded proteins can be used for a number of purposes. Examples include, early detection of breast or lung cancers, monitoring and early detection of relapse following treatment of breast or lung cancers including early detection of metastatic cancer, monitoring response to therapy of breast or lung cancers, determining prognosis of breast or lung cancers, directing therapy of breast or lung cancers, selecting patients for postoperative chemotherapy or radiation therapy, selecting therapy, determining tumor prognosis and the likelihood that a given cancer will metastasize or has metastasized, treatment, or response to treatment, early detection of precancerous conditions and early detection of metastasis. Other aspects of the invention will become apparent to the skilled artisan by the following description of the invention. In one aspect, the present invention provides a method of detecting a metastatic breast or lung cancer-associated transcript in a cell from a patient, the method comprising contacting a biological sample from the patient with a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C.
In one embodiment, the polynucleotide selectively hybridizes to a sequence at least 95%o identical to a sequence as shown in Tables 1A-12C. In another embodiment, the polynucleotide comprises a sequence as shown in Tables 1 A-12C.
In one embodiment, the biological sample is a tissue sample. In another embodiment, the biological sample comprises isolated nucleic acids, e.g., mRNA.
In one embodiment, the polynucleotide is labeled, e.g., with a fluorescent label. In one embodiment, the polynucleotide is immobilized on a solid surface.
In one embodiment, the patient is undergoing a therapeutic regimen to treat metastatic breast or lung cancer. In another embodiment, the metastatic breast or lung cancer has metastasized to the brain.
In one embodiment, the patient is a human. In one embodiment, the method further comprises the step of amplifying nucleic acids before the step of contacting the biological sample with the polynucleotide.
In another aspect, the present invention provides methods of detecting polypeptide encoded by a metastatic breast or lung cancer-associated transcript in a cell from a patient, the method comprising contacting a biological sample from the patient with an antibody that specifically binds a polypeptide encoded by a sequence at least 80%> identical to a sequence as shown in Tables 1 A-12C.
In another aspect, the present invention provides a method of monitoring the efficacy of a therapeutic treatment of metastatic breast or lung cancer, the method comprising the steps of: (i) providing a biological sample from a patient undergoing the therapeutic treatment; and (ii) determining the level of a metastatic breast or lung cancer-associated transcript in the biological sample by contacting the biological sample with a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C, thereby monitoring the efficacy of the therapy. In one embodiment, the method further comprises the step of: (iii) comparing the level of the metastatic breast or lung cancer-associated transcript to a level of the metastatic breast or lung cancer-associated transcript in a biological sample from the patient prior to, or earlier in, the therapeutic treatment. In another aspect, the present invention provides a method of monitoring the efficacy of a therapeutic treatment of metastatic breast or lung cancer, the method comprising the steps of: (i) providing a biological sample from a patient undergoing the therapeutic treatment; and (ii) determining the level of a metastatic breast or lung cancer-associated antibody in the biological sample by contacting the biological sample with a polypeptide encoded by a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C, wherein the polypeptide specifically binds to the metastatic breast or lung cancer-associated antibody, thereby monitoring the efficacy of the therapy.
In one embodiment, the method further comprises the step of: (iii) comparing the level of the metastatic breast or lung cancer-associated antibody to a level of the metastatic breast or lung cancer-associated antibody in a biological sample from the patient prior to, or earlier in, the therapeutic treatment.
In another aspect, the present invention provides a method of monitoring the efficacy of a therapeutic treatment of metastatic breast or lung cancer, the method comprising the steps of: (i) providing a biological sample from a patient undergoing the therapeutic treatment; and (ii) determining the level of a metastatic breast or lung cancer-associated polypeptide in the biological sample by contacting the biological sample with an antibody, wherein the antibody specifically binds to a polypeptide encoded by a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1 A- 12C, thereby monitoring the efficacy of the therapy.
In one embodiment, the method further comprises the step of: (iii) comparing the level of the metastatic breast or lung cancer-associated polypeptide to a level of the metastatic breast or lung cancer-associated polypeptide in a biological sample from the patient prior to, or earlier in, the therapeutic treatment. In one aspect, the present invention provides an isolated nucleic acid molecule consisting of a polynucleotide sequence as shown in Tables 1 A-12C.
In one embodiment, an expression vector or cell comprises the isolated nucleic acid. In one aspect, the present invention provides an isolated polypeptide which is encoded by a nucleic acid molecule having polynucleotide sequence as shown in Tables 1 A- 12C.
In another aspect, the present invention provides an antibody that specifically binds to an isolated polypeptide which is encoded by a nucleic acid molecule having polynucleotide sequence as shown in Tables 1 A-12C.
In one embodiment, the antibody is conjugated to an effector component, e.g., a fluorescent label, a radioisotope or a cytotoxic chemical.
In one embodiment, the antibody is an antibody fragment. In another embodiment, the antibody is humanized.
In one aspect, the present invention provides a method of detecting a metastatic breast or lung cancer cell in a biological sample from a patient, the method comprising contacting the biological sample with an antibody as described herein.
In another aspect, the present invention provides a method of detecting antibodies specific to metastatic breast or lung cancer in a patient, the method comprising contacting a biological sample from the patient with a polypeptide encoded by a nucleic acid comprises a sequence from Tables 1A-12C.
In another aspect, the present invention provides a method for identifying a compound that modulates a metastatic breast or lung cancer-associated polypeptide, the method comprising the steps of: (i) contacting the compound with a metastatic breast or lung cancer-associated polypeptide, the polypeptide encoded by a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1A-12C; and (ii) determining the functional effect of the compound upon the polypeptide.
In one embodiment, the functional effect is a physical effect, an enzymatic effect, or a chemical effect.
In one embodiment, the polypeptide is expressed in a eukaryotic host cell or cell membrane. In another embodiment, the polypeptide is recombinant.
In one embodiment, the functional effect is determined by measuring ligand binding to the polypeptide. In another aspect, the present invention provides a method of inhibiting proliferation of a metastatic breast or lung cancer-associated cell to treat breast or lung cancer in a patient, the method comprising the step of administering to the subject a therapeutically effective amount of a compound identified as described herein.
In one embodiment, the compound is an antibody. In another aspect, the present invention provides a drag screening assay comprising the steps of: (i) administering a test compound to a mammal having metastatic breast or lung cancer or a cell isolated therefrom; (ii) comparing the level of gene expression of a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence as shown in Tables 1 A-12C in a treated cell or mammal with the level of gene expression of the polynucleotide in a control cell or mammal, wherein a test compound that modulates the level of expression of the polynucleotide is a candidate for the treatment of metastatic breast or lung cancer.
In one embodiment, the control is a mammal with metastatic breast or lung cancer or a cell therefrom that has not been treated with the test compound. In another embodiment, the control is a normal cell or mammal.
In another aspect, the present invention provides a method for treating a mammal having metastatic breast or lung cancer comprising administering a compound identified by the assay described herein. In another aspect, the present invention provides a pharmaceutical composition for treating a mammal having meta static breast or lung cancer, the composition comprising a compound identified by the assay described herein and a physiologically acceptable excipient.
DETAILED DESCRIPTION OF THE INVENTION
In accordance with the objects outlined above, the present invention provides novel methods for diagnosis and treatment of metastatic breast or metastatic lung cancer. The invention is useful for the treatment of metastatic breast and metastatic lung cancer when the cancer is metastasized to the brain, as well as when the cancer is metastasized to other organs and tissues. The invention also provides methods of screening for compositions which modulate metastatic breast cancer or metastatic lung cancer.
Primary tumors are classified by the type of tissue from which they arise, metastatic tumors are classified by the tissue type from which the cancer cells are derived. Almost any cancer can metastasize. The metastases may occur to any site, however some cancers preferentially metastasize to particular organs. For example lung, breast, head & neck, cervical, and bladder tumors frequently metastasize to particular organs. Specifically, lung cancer metastatisizes to: brain, bone, liver, adrenal glands, lung, pleura, subcutaneous tissue, kidney, lymph nodes, cerebrospinal fluid, pancreas, bone marrow. Breast cancer metastatisizes to: lymph nodes, breast, abdominal viscera, lungs, bones, liver, adrenal glands, brain, meninges, pleura, cerebrospinal fluid. Head and neck cancer metastatisizes to: lung, esophagus, upper aerodigestive tract, lymph nodes, oral cavity, nasal cavity. Cervical cancer metastatisizes to: vagina, paracervical spaces, bladder, rectum, pelvic wall, lymph nodes. Bladder cancer metastatisizes to: prostate, uterus, vagina, bowel, pelvic wall, lymph nodes, and perivesical fat.
Brain metastases are a particular concern because of the deadly nature of brain tumors in general. Because the brain is generally unforgiving in its response to both the tumor and therapy, prognosis in cases metastatic brain tumors is especially poor. This is the case whether or not the primary cancer is treatable or even cured.
Whether or not cancer cells metastasize to the brain or other parts of the body depends on many factors including the type of cancer, stage of cancer, and original location of the cancer. Treatment for secondary (metastatic) tumors depends on where the cancer started and the extent of the spread as well as other factors, including the patient's age, general health, and response to previous treatment.
Knowing the origin of metastatic cancer can greatly improve the probable outcome of treatment for individuals with metastatic disease. Indeed, the earlier metastatic cancer can be detected, the better is the prognosis for the individual since it is often metastatic burden that kills a patient. Because metastatic burden increases with time, early detection is essential for successful treatment.
Thus, in accordance with the objectives of the invention, Tables 1A-12C provide UniGene cluster identification numbers for the nucleotide sequence of genes that exhibit increased or decreased expression in metastasizing breast and lung cancer samples. Tables 1 A-12C also provide an exemplar accession number that provides a nucleotide sequence that is part of the UniGene cluster.
Table 1 A shows about 461 genes upregulated in breast metastases to the brain relative to normal breast tissues. Table 2 A shows about 445 genes upregulated in breast metastases to the brain relative to normal body tissues. Table 3 A shows about 216 genes upregulated in breast metastases to the brain relative to primary breast tumors. Table 4 A shows about 350 genes downregulated in breast metastases to the brain relative to primary breast tumors. Table 5 A shows about 489 genes downregulated in breast metastases to the brain relative to normal breast tissue. Table 6A shows about 1251 genes upregulated in lung metastases to the brain relative to normal lung tissues. Table 7 A shows about 381 genes upregulated in lung metastases to the brain relative to normal body tissues. Table 8A shows about 330 genes upregulated in lung metastases to the brain relative to primary lung tumors. Table 9A shows about 252 genes downregulated in lung metastases to the brain relative to primary lung tumors. Table 10A shows about 289 genes downregulated in lung metastases to the brain relative to normal lung tissue. Table 11 A shows about 1198 genes upregulated in breast and lung metastases to the brain relative to normal body tissues. Table 12A shows about 2867 genes upregulated in breast and lung metastases to the brain relative to normal breast and lung tissues.
Although the Tables and analysis herein is derived primarily from metastases to the brain, it is expected that markers identified from these samples should also be expressed in metastasis to other organs, particularly metastasis originating from tumors in the lung, breast, head and neck, cervix, and bladder. Indeed, the tumor-specific genes expressed in lung tumors are often also expressed in head and neck, cervical, and bladder tumors Therefore, the genes identified in metastases of primary lung tumors may also be expressed in primary tumors and metastases arising from primary tumors of the nasal cavity, paranasal sinuses, nasopharynx, oral cavity, oral pharynx, lip, larynx, hypopharynx, salivary glands, paragangliomas, esophagus, cervix, vagina, vulva, or bladder. Thus, the identified metastatic markers should be useful in diagnosis, prognosis, or therapy of metastases from these cancers.
Furthermore, one of skill will recognize that although the sequences identified in Tables 1 A-12C exhibited increased or decreased expression in metastasizing breast or lung cancer samples, the sequences of the invention, and their encoded proteins, can also be used to diagnose, treat or prevent cancers in patients with non-metastatic breast cancers or non- metastatic lung cancers. Alteration of gene expression for a gene in Tables 1A-12C may be more likely or less likely to indicate that the subject will progress to metastatic disease. The sequences can also be used to diagnose, treat or prevent precancerous or benign conditions. Alteration of gene expression for a gene in Tables 1A-12C may or may not indicate that the subject is more likely to progress to cancer or to metastatic disease. Thus, although the specification focuses primarily on metastasizing breast or lung cancer, the methods described below can also be applied to non-metastasizing breast or lung cancers and precancerous or benign conditions as well. Definitions
The term "metastatic breast cancer protein" or "metastatic breast cancer polynucleotide" or "metastatic breast cancer-associated transcript" refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a nucleotide sequence of or associated with a UniGene cluster of Tables 1-5, 11, and 12; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence encoded by a nucleotide sequence of or associated with a UniGene cluster of Tables 1-5, 11, and 12, and conservatively modified variants thereof; (3) specifically hybridize under stringent hybridization conditions to a nucleic acid sequence, or the complement thereof of Tables 1-5, 11, and 12 and conservatively modified variants thereof or (4) have an amino acid sequence that has greater than about 60% amino acid sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater amino sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more amino acid, to an amino acid sequence encoded by a nucleotide sequence of or associated with a UniGene cluster of Tables 1-5, 11, and 12. A polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal. A "metastatic breast cancer polypeptide" and a "metastatic breast cancer polynucleotide," include both naturally occurring or recombinant.
The term "metastatic lung cancer protein" or "metastatic lung cancer polynucleotide" or "metastatic lung cancer-associated transcript" refers to nucleic acid and polypeptide polymorphic variants, alleles, mutants, and interspecies homologs that: (1) have a nucleotide sequence that has greater than about 60% nucleotide sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater nucleotide sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500, 1000, or more nucleotides, to a nucleotide sequence of or associated with a UniGene cluster of Tables 6A-12C; (2) bind to antibodies, e.g., polyclonal antibodies, raised against an immunogen comprising an amino acid sequence encoded by a nucleotide sequence of or associated with a UniGene cluster of Tables 6A-12C, and conservatively modified variants thereof; (3) specifically hybridize under stringent hybridization conditions to a nucleic acid sequence, or the complement thereof of Tables 6A- 12C and conservatively modified variants thereof or (4) have an amino acid sequence that has greater than about 60% amino acid sequence identity, 65%, 70%, 75%, 80%, 85%, 90%, preferably 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% or 99% or greater amino sequence identity, preferably over a region of over a region of at least about 25, 50, 100, 200, 500,
1000, or more amino acid, to an amino acid sequence encoded by a nucleotide sequence of or associated with a UniGene cluster of Tables 6A-12C. A polynucleotide or polypeptide sequence is typically from a mammal including, but not limited to, primate, e.g., human; rodent, e.g., rat, mouse, hamster; cow, pig, horse, sheep, or other mammal. A "metastatic lung cancer polypeptide" and a "metastatic lung cancer polynucleotide," include both naturally occurring or recombinant.
The term "metastasis" refers to the process by which a disease shifts from from one part of the body to another. This process may include the spreading of neoplasms from the site of a primary tumor to distant parts of the body. The term "metastatic brain tumor" refers to a tumor of the brain and/or its associated bone, blood vessels, meninges etc that has developed as a result of the metastasis of cancer from a primary site to the brain.
The term "secondary brain tumor" refers to a metastatic brain tumor as defined above. The term "metastatic breast cancer" refers to any cancer in any part of the body which has its origins in breast cancer tissue. Metastatic breast cancer includes, but is not limited to "metastatic brain tumors" that have their origin in a primary breast cancer, and pre- metastatic primary tumor cells in the process of developing a metastatic phenotype.
The term "metastatic lung cancer" refers to any cancer in any part of the body which has its origins in lung cancer tissue. Metastatic lung cancer includes, but is not limited to "metastatic brain tumors" that have their origin in a primary lung cancer, and pre-metastatic primary tumor cells in the process of developing a metastatic phenotype.
A "full length" metastatic breast or lung cancer protein or nucleic acid refers to a metastatic breast or lung cancer polypeptide or polynucleotide sequence, or a variant thereof, that contains all of the elements normally contained in one or more naturally occurring, wild type metastatic breast or lung cancer polynucleotide or polypeptide sequences. The "full length" may be prior to, or after, various stages of post-translation processing or splicing, including alternative splicing. "Biological sample" as used herein is a sample of biological tissue or fluid that contains nucleic acids or polypeptides, e.g., of a metastatic breast or lung cancer protein, polynucleotide or transcript. Such samples include, but are not limited to, tissue isolated from primates, e.g., humans, or rodents, e.g., mice, and rats. Biological samples may also include sections of tissues such as biopsy and autopsy samples, frozen sections taken for histologic purposes, blood, plasma, serum, sputum, stool, tears, mucus, hair, skin, etc. Biological samples also include explants and primary and/or transformed cell cultures derived from patient tissues. A biological sample is typically obtained from a eukaryotic organism, most preferably a mammal such as a primate, e.g., chimpanzee or human; cow; dog; cat; a rodent, e.g., guinea pig, rat, mouse; rabbit; or other mammal; or a bird; reptile; fish.
"Providing a biological sample" means to obtain a biological sample for use in methods described in this invention. Most often, this will be done by removing a sample of cells from an animal, but can also be accomplished by using previously isolated cells (e.g., isolated by another person, at another time, and/or for another purpose), or by performing the methods of the invention in vivo. Archival tissues, having treatment or outcome history, will be particularly useful.
The terms "identical" or percent "identity," in the context of two or more nucleic acids or polypeptide sequences, refer to two or more sequences or subsequences that are the same or have a specified percentage of amino acid residues or nucleotides that are the same (i.e., about 60% identity, preferably 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%o, 97%>, 98%>, 99%o, or higher identity over a specified region, when compared and aligned for maximum correspondence over a comparison window or designated region) as measured using a BLAST or BLAST 2.0 sequence comparison algorithms with default parameters described below, or by manual alignment and visual inspection. Such sequences are then said to be "substantially identical." This definition also refers to, or may be applied to, the compliment of a test sequence. The definition also includes sequences that have deletions and/or additions, as well as those that have substitutions, as well as naturally occurring, e.g., polymorphic or allelic variants, and man-made variants. As described below, the preferred algorithms can account for gaps and the like. Preferably, identity exists over a region that is at least about 25 amino acids or nucleotides in length, or more preferably over a region that is 50-100 amino acids or nucleotides in length.
For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are entered into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. Preferably, default program parameters can be used, or alternative parameters can be designated. The sequence comparison algorithm then calculates the percent sequence identities for the test sequences relative to the reference sequence, based on the program parameters.
A "comparison window", as used herein, includes reference to a segment of one of the number of contiguous positions selected from the group consisting typically of from 20 to 600, usually about 50 to about 200, more usually about 100 to about 150 in which a sequence may be compared to a reference sequence of the same number of contiguous positions after the two sequences are optimally aligned. Methods of alignment of sequences for comparison are well-known in the art. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman, Adv. Appl. Math. 2:482 (1981), by the homology alignment algorithm of Needleman & Wunsch, J. Mol. Biol. 48:443 (1970), by the search for similarity method of Pearson & Lipman, Proc. Nat 'I. Acad. Sci. USA 85:2444 (1988), by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, WI), or by manual alignment and visual inspection (see, e.g., Current Protocols in Molecular Biology (Ausubel et al., eds. 1995 supplement)).
Preferred examples of algorithms that are suitable for determining percent sequence identity and sequence similarity include the BLAST and BLAST 2.0 algorithms, which are described in Altschul et al, Nuc. Acids Res. 25:3389-3402 (1977) and Altschul et al., J. Mol. Biol. 215:403-410 (1990). BLAST and BLAST 2.0 are used, with the parameters described herein, to determine percent sequence identity for the nucleic acids and proteins of the invention. Software for performing BLAST analyses is publicly available through the National Center for Biotechnology Information. This algorithm involves first identifying high scoring sequence pairs (HSPs) by identifying short words of length W in the query sequence, which either match or satisfy some positive- valued threshold score T when aligned with a word of the same length in a database sequence. T is referred to as the neighborhood word score threshold (Altschul et al, supra). These initial neighborhood word hits act as seeds for initiating searches to find longer HSPs containing them. The word hits are extended in both directions along each sequence for as far as the cumulative alignment score can be increased. Cumulative scores are calculated using, e.g., for nucleotide sequences, the parameters M (reward score for a pair of matching residues; always > 0) and N (penalty score for mismatching residues; always < 0). For amino acid sequences, a scoring matrix is used to calculate the cumulative score. Extension of the word hits in each direction are halted when: the cumulative alignment score falls off by the quantity X from its maximum achieved value; the cumulative score goes to zero or below, due to the accumulation of one or more negative- scoring residue alignments; or the end of either sequence is reached. The BLAST algorithm parameters W, T, and X determine the sensitivity and speed of the alignment. The BLASTN program (for nucleotide sequences) uses as defaults a wordlength (W) of 11, an expectation (E) of 10, M=5, N=-4 and a comparison of both strands. For amino acid sequences, the BLASTP program uses as defaults a wordlength of 3, and expectation (E) of 10, and the BLOSUM62 scoring matrix (see Henikoff & Henikoff, Proc. Natl. Acad. Sci. USA 89:10915 (1989)) alignments (B) of 50, expectation (E) of 10, M=5, N=-4, and a comparison of both strands.
The BLAST algorithm also performs a statistical analysis of the similarity between two sequences (see, e.g., Karlin & Altschul, Proc. N t 7. Acad. Sci. USA 90:5873-5787 (1993)). One measure of similarity provided by the BLAST algorithm is the smallest sum probability (P(Ν)), which provides an indication of the probability by which a match between two nucleotide or amino acid sequences would occur by chance. For example, a nucleic acid is considered similar to a reference sequence if the smallest sum probability in a comparison of the test nucleic acid to the reference nucleic acid is less than about 0.2, more preferably less than about 0.01 , and most preferably less than about 0.001. Log values may be large negative numbers, e.g., 5, 10, 20, 30, 40, 40, 70, 90, 110, 150, 170, etc.
An indication that two nucleic acid sequences or polypeptides are substantially identical is that the polypeptide encoded by the first nucleic acid is immunologically cross reactive with the antibodies raised against the polypeptide encoded by the second nucleic acid, as described below. Thus, a polypeptide is typically substantially identical to a second polypeptide, e.g., where the two peptides differ only by conservative substitutions. Another indication that two nucleic acid sequences are substantially identical is that the two molecules or their complements hybridize to each other under stringent conditions, as described below. Yet another indication that two nucleic acid sequences are substantially identical is that the same primers can be used to amplify the sequences. A "host cell" is a naturally occurring cell or a transformed cell that contains an expression vector and supports the replication or expression of the expression vector. Host cells may be cultured cells, explants, cells in vivo, and the like. Host cells may be prokaryotic cells such as E. coli, or eukaryotic cells such as yeast, insect, amphibian, or mammalian cells such as CHO, HeLa, and the like (see, e.g., the American Type Culture Collection catalog or web site, www.atcc.org).
The terms "isolated," "purified," or "biologically pure" refer to material that is substantially or essentially free from components that normally accompany it as found in its native state. Purity and homogeneity are typically determined using analytical chemistry techniques such as polyacrylamide gel electrophoresis or high performance liquid chromatography. A protein or nucleic acid that is the predominant species present in a preparation is substantially purified. In particular, an isolated nucleic acid is separated from some open reading frames that naturally flank the gene and encode proteins other than protein encoded by the gene. The term "purified" in some embodiments denotes that a nucleic acid or protein gives rise to essentially one band in an electrophoretic gel. Preferably, it means that the nucleic acid or protein is at least 85% pure, more preferably at least 95% pure, and most preferably at least 99%> pure. "Purify" or "purification" in other embodiments means removing at least one contaminant from the composition to be purified. In this sense, purification does not require that the purified compound be homogenous, e.g., 100% pure.
The terms "polypeptide," "peptide" and "protein" are used interchangeably herein to refer to a polymer of amino acid residues. The terms apply to amino acid polymers in which one or more amino acid residue is an artificial chemical mimetic of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers, those containing modified residues, and non-naturally occurring amino acid polymer.
The term "amino acid" refers to naturally occurring and synthetic amino acids, as well as amino acid analogs and amino acid mimetics that function similarly to the naturally occurring amino acids. Naturally occurring amino acids are those encoded by the genetic code, as well as those amino acids that are later modified, e.g., hydroxyproline, γ- carboxyglutamate, and O-phosphoserine. Amino acid analogs refers to compounds that have the same basic chemical structure as a naturally occurring amino acid, e.g., an carbon that is bound to a hydrogen, a carboxyl group, an amino group, and an R group, e.g., homoserine, norleucine, methionine sulfoxide, methionine methyl sulfonium. Such analogs may have modified R groups (e.g., norleucine) or modified peptide backbones, but retain the same basic chemical structure as a naturally occurring amino acid. Amino acid mimetics refers to chemical compounds that have a structure that is different from the general chemical structure of an amino acid, but that functions similarly to a naturally occurring amino acid.
Amino acids may be referred to herein by either their commonly known three letter symbols or by the one-letter symbols recommended by the IUPAC-IUB Biochemical Nomenclature Commission. Nucleotides, likewise, may be referred to by their commonly accepted single-letter codes.
"Conservatively modified variants" applies to both amino acid and nucleic acid sequences. With respect to particular nucleic acid sequences, conservatively modified variants refers to those nucleic acids which encode identical or essentially identical amino acid sequences, or where the nucleic acid does not encode an amino acid sequence, to essentially identical or associated, e.g., naturally contiguous, sequences. Because of the degeneracy of the genetic code, a large number of functionally identical nucleic acids encode most proteins. For instance, the codons GCA, GCC, GCG and GCU all encode the amino acid alanine. Thus, at every position where an alanine is specified by a codon, the codon can be altered to another of the corresponding codons described without altering the encoded polypeptide. Such nucleic acid variations are "silent variations," which are one species of conservatively modified variations. Every nucleic acid sequence herein which encodes a polypeptide also describes silent variations of the nucleic acid. One of skill will recognize that in certain contexts each codon in a nucleic acid (except AUG, which is ordinarily the only codon for methionine, and TGG, which is ordinarily the only codon for tryptophan) can be modified to yield a functionally identical molecule. Accordingly, often silent variations of a nucleic acid which encodes a polypeptide is implicit in a described sequence with respect to the expression product, but not with respect to actual probe sequences. As to amino acid sequences, one of skill will recognize that individual substitutions, deletions or additions to a nucleic acid, peptide, polypeptide, or protein sequence which alters, adds or deletes a single amino acid or a small percentage of amino acids in the encoded sequence is a "conservatively modified variant" where the alteration results in the substitution of an amino acid with a chemically similar amino acid. Conservative substitution tables providing functionally similar amino acids are well known in the art. Such conservatively modified variants are in addition to and do not exclude polymorphic variants, interspecies homologs, and alleles of the invention.
The following eight groups each contain amino acids that are typically conservative substitutions for one another: 1) Alanine (A), Glycine (G); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W); 7) Serine (S), Threonine (T); and 8) Cysteine (C), Methionine (M) (see, e.g., Creighton, Proteins (1984)). Macromolecular structures such as polypeptide structures can be described in terms of various levels of organization. For a general discussion of this organization, see, e.g., Alberts et al, Molecular Biology of the Cell (3rd ed., 1994) and Cantor & Schimmel, Biophysical Chemistiy Part I: The Conformation of Biological Macromolecules (1980). "Primary structure" refers to the amino acid sequence of a particular peptide. "Secondary structure" refers to locally ordered, three dimensional structures within a polypeptide. These structures are commonly known as domains. Domains are portions of a polypeptide that often form a compact unit of the polypeptide and are typically 25 to approximately 500 amino acids long. Typical domains are made up of sections of lesser organization such as stretches of β-sheet and α-helices. "Tertiary structure" refers to the complete three dimensional structure of a polypeptide monomer. "Quaternary structure" refers to the three dimensional structure formed, usually by the noncovalent association of independent tertiary units. Anisotropic terms are also known as energy terms.
"Nucleic acid" or "oligonucleotide" or "polynucleotide" or grammatical equivalents used herein means at least two nucleotides covalently linked together. Oligonucleotides are typically from about 5, 6, 7, 8, 9, 10, 12, 15, 25, 30, 40, 50 or more nucleotides in length, up to about 100 nucleotides in length. Nucleic acids and polynucleotides are a polymers of any length, including longer lengths, e.g., 200, 300, 500, 1000, 2000, 3000, 5000, 7000, 10,000, etc. A nucleic acid of the present invention will generally contain phosphodiester bonds, although in some cases, nucleic acid analogs are included that may have alternate backbones, comprising, e.g., phosphoramidate, phosphorothioate, phosphorodithioate, or O- methylphophoroamidite linkages (see Eckstein, Oligonucleotides and Analogues: A Practical Approach, Oxford University Press); and peptide nucleic acid backbones and linkages. Other analog nucleic acids include those with positive backbones; non-ionic backbones, and non- ribose backbones, including those described in U.S. Patent Nos. 5,235,033 and 5,034,506, and Chapters 6 and 7, ASC Symposium Series 580, Carbohydrate Modifications in Antisense Research, Sanghui & Cook, eds.. Nucleic acids containing one or more carbocyclic sugars are also included within one definition of nucleic acids. Modifications of the ribose- phosphate backbone may be done for a variety of reasons, e.g. to increase the stability and half-life of such molecules in physiological environments or as probes on a biochip. Mixtures of naturally occurring nucleic acids and analogs can be made; alternatively, mixtures of different nucleic acid analogs, and mixtures of naturally occurring nucleic acids and analogs may be made. Particularly preferred are peptide nucleic acids (PNA) which includes peptide nucleic acid analogs. These backbones are substantially non-ionic under neutral conditions, in contrast to the highly charged phosphodiester backbone of naturally occurring nucleic acids. This results in two advantages. First, the PNA backbone exhibits improved hybridization kinetics. PNAs have larger changes in the melting temperature (Tm) for mismatched versus perfectly matched basepairs. DNA and RNA typically exhibit a 2-4°C drop in Tm for an internal mismatch. With the non-ionic PNA backbone, the drop is closer to 7-9°C. Similarly, due to their non-ionic nature, hybridization of the bases attached to these backbones is relatively insensitive to salt concentration. In addition, PNAs are not degraded by cellular enzymes, and thus can be more stable.
The nucleic acids may be single stranded or double stranded, as specified, or contain portions of both double stranded or single stranded sequence. As will be appreciated by those in the art, the depiction of a single strand also defines the sequence of the complementary strand; thus the sequences described herein also provide the complement of the sequence. The nucleic acid may be DNA, both genomic and cDNA, RNA or a hybrid, where the nucleic acid may contain combinations of deoxyribo- and ribo-nucleotides, and combinations of bases, including uracil, adenine, thymine, cytosine, guanine, inosine, xanthine hypoxanthine, isocytosine, isoguanine, etc. "Transcript" typically refers to a naturally occurring RNA, e.g., a pre-mRNA, linRNA, or mRNA. As used herein, the term "nucleoside" includes nucleotides and nucleoside and nucleotide analogs, and modified nucleosides such as amino modified nucleosides. In addition, "nucleoside" includes non-naturally occurring analog structures. Thus, e.g. the individual units of a peptide nucleic acid, each containing a base, are referred to herein as a nucleoside.
A "label" or a "detectable moiety" is a composition detectable by spectroscopic, photochemical, biochemical, immunochemical, chemical, or other physical means. For example, useful labels include 32P, fluorescent dyes, electron-dense reagents, enzymes (e.g., as commonly used in an ELISA), biotin, digoxigenin, or haptens and proteins or other entities which can be made detectable, e.g., by incorporating a radiolabel into the peptide or used to detect antibodies specifically reactive with the peptide. An "effector" or "effector moiety" or "effector component" is a molecule that is bound (or linked, or conjugated), either covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds, to an antibody. The "effector" can be a variety of molecules including, e.g., detection moieties including radioactive compounds, fluorescent compounds, an enzyme or substrate, tags such as epitope tags, a toxin; activatable moieties, a chemotherapeutic agent; a lipase; an antibiotic; or a radioisotope emitting "hard" e.g., beta radiation.
A "labeled nucleic acid probe or oligonucleotide" is one that is bound, either covalently, through a linker or a chemical bond, or noncovalently, through ionic, van der Waals, electrostatic, or hydrogen bonds to a label such that the presence of the probe may be detected by detecting the presence of the label bound to the probe. Alternatively, method using high affinity interactions may achieve the same results where one of a pair of binding partners binds to the other, e.g., biotin, streptavidin.
As used herein a "nucleic acid probe or oligonucleotide" is defined as a nucleic acid capable of binding to a target nucleic acid of complementary sequence through one or more types of chemical bonds, usually through complementary base pairing, usually through hydrogen bond formation. As used herein, a probe may include natural (i.e., A, G, C, or T) or modified bases (7-deazaguanosine, inosine, etc.). In addition, the bases in a probe may be joined by a linkage other than a phosphodiester bond, so long as it does not functionally interfere with hybridization. Thus, e.g., probes may be peptide nucleic acids in which the constituent bases are joined by peptide bonds rather than phosphodiester linkages. It will be understood by one of skill in the art that probes may bind target sequences lacking complete complementarity with the probe sequence depending upon the stringency of the hybridization conditions. The probes are preferably directly labeled as with isotopes, chromophores, lumiphores, chromogens, or indirectly labeled such as with biotin to which a streptavidin complex may later bind. By assaying for the presence or absence of the probe, one can detect the presence or absence of the select sequence or subsequence. Diagnosis or prognosis may be based at the genomic level, or at the level of RNA or protein expression.
The term "recombinant" when used with reference, e.g., to a cell, or nucleic acid, protein, or vector, indicates that the cell, nucleic acid, protein or vector, has been modified by the introduction of a heterologous nucleic acid or protein or the alteration of a native nucleic acid or protein, or that the cell is derived from a cell so modified. Thus, e.g., recombinant cells express genes that are not found within the native (non-recombinant) form of the cell or express native genes that are otherwise abnormally expressed, under expressed or not expressed at all. By the term "recombinant nucleic acid" herein is meant nucleic acid, originally formed in vitro, in general, by the manipulation of nucleic acid, e.g., using pofymerases and endonucleases, in a form not normally found in nature. In this manner, operably linkage of different sequences is achieved. Thus an isolated nucleic acid, in a linear form, or an expression vector formed in vitro by ligating DNA molecules that are not normally joined, are both considered recombinant for the purposes of this invention. It is understood that once a recombinant nucleic acid is made and reintroduced into a host cell or organism, it will replicate non-recombinantly, i.e., using the hi vivo cellular machinery of the host cell rather than in vitro manipulations; however, such nucleic acids, once produced recombinantly, although subsequently replicated non-recombinantly, are still considered recombinant for the purposes of the invention. Similarly, a "recombinant protein" is a protein made using recombinant techniques, i.e., through the expression of a recombinant nucleic acid as depicted above.
The term "heterologous" when used with reference to portions of a nucleic acid indicates that the nucleic acid comprises two or more subsequences that are not normally found in the same relationship to each other in nature. For instance, the nucleic acid is typically recombinantly produced, having two or more sequences, e.g., from unrelated genes arranged to make a new functional nucleic acid, e.g., a promoter from one source and a coding region from another source. Similarly, a heterologous protein will often refer to two or more subsequences that are not found in the same relationship to each other in nature (e.g., a fusion protein).
A "promoter" is defined as an array of nucleic acid control sequences that direct transcription of a nucleic acid. As used herein, a promoter mcludes necessary nucleic acid sequences near the start site of transcription, such as, in the case of a polymerase II type promoter, a TATA element. A promoter also optionally includes distal enhancer or repressor elements, which can be located as much as several thousand base pairs from the start site of transcription. A "constitutive" promoter is a promoter that is active under most environmental and developmental conditions. An "inducible" promoter is a promoter that is active under environmental or developmental regulation. The term "operably linked" refers to a functional linkage between a nucleic acid expression control sequence (such as a promoter, or array of transcription factor binding sites) and a second nucleic acid sequence, wherein the expression control sequence directs transcription of the nucleic acid corresponding to the second sequence.
An "expression vector" is a nucleic acid construct, generated recombinantly or synthetically, with a series of specified nucleic acid elements that permit transcription of a particular nucleic acid in a host cell. The expression vector can be part of a plasmid, virus, or nucleic acid fragment. Typically, the expression vector includes a nucleic acid to be transcribed operably linked to a promoter. The phrase "selectively (or specifically) hybridizes to" refers to the binding, duplexing, or hybridizing of a molecule only to a particular nucleotide sequence under stringent hybridization conditions when that sequence is present in a complex mixture (e.g., total cellular or library DNA or RNA). The phrase "stringent hybridization conditions" refers to conditions under which a probe will hybridize to its target subsequence, typically in a complex mixture of nucleic acids, but to essentially no other sequences. Stringent conditions are sequence-dependent and will be different in different circumstances. Longer sequences hybridize specifically at higher temperatures. An extensive guide to the hybridization of nucleic acids is found in Tijssen, Techniques in Biochemistry and Molecular Biology— Hybridization with Nucleic Probes, "Overview of principles of hybridization and the strategy of nucleic acid assays" (1993). Generally, stringent conditions are selected to be about 5-10°C lower than the thermal melting point (Tm) for the specific sequence at a defined ionic strength pH. The Tm is the temperature (under defined ionic strength, pH, and nucleic concentration) at which 50% of the probes complementary to the target hybridize to the target sequence at equilibrium (as the target sequences are present in excess, at Tm, 50% of the probes are occupied at equilibrium). Stringent conditions will be those in which the salt concentration is less than about 1.0 M sodium ion, typically about 0.01 to 1.0 M sodium ion concentration (or other salts) at pH 7.0 to 8.3 and the temperature is at least about 30°C for short probes (e.g., 10 to 50 nucleotides) and at least about 60°C for long probes (e.g., greater than 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. For selective or specific hybridization, a positive signal is at least two times background, preferably 10 times background hybridization. Exemplary stringent hybridization conditions are often: 50% formamide, 5x SSC, and 1% SDS, incubating at 42°C, or, 5x SSC, 1% SDS, incubating at 65°C, with wash in 0.2x SSC, and 0.1% SDS at 65°C. For PCR, a temperature of about 36°C is typical for low stringency amplification, although annealing temperatures may vary between about 32°C and 48°C depending on primer length. For high stringency PCR amplification, a temperature of about 62°C is typical, although high stringency annealing temperatures can range from about 50°C to about 65°C, depending on the primer length and specificity. Typical cycle conditions for both high and low stringency amplifications include a denaturation phase of 90°C - 95°C for 30 sec - 2 min., an annealing phase lasting 30 sec. - 2 min., and an extension phase of about 72°C for 1 - 2 min. Protocols and guidelines for low and high stringency amplification reactions are provided, e.g., in Innis et al, PCR Protocols, A Guide to Methods and Applications (1990).
Nucleic acids that do not hybridize to each other under stringent conditions are still substantially identical if the polypeptides which they encode are substantially identical. This occurs, e.g., when a copy of a nucleic acid is created using the maximum codon degeneracy permitted by the genetic code. In such cases, the nucleic acids typically hybridize under moderately stringent hybridization conditions. Exemplary "moderately stringent hybridization conditions" include a hybridization in a buffer of 40% formamide, 1 M NaCl, 1% SDS at 37°C, and a wash in IX SSC at 45°C. A positive hybridization is at least twice background. Those of ordinary skill will readily recognize that alternative hybridization and wash conditions can be utilized to provide conditions of similar stringency. Additional guidelines for determining hybridization parameters are provided in numerous reference, e.g., see, e.g., Current Protocols in Molecular Biology (Ausubel et al, eds. 1995 supplement).
The phrase "functional effects" in the context of assays for testing compounds that modulate activity of a metastatic breast cancer or metastatic lung cancer protein includes the determination of a parameter that is indirectly or directly under the influence of the metastatic breast cancer or metastatic lung cancer protein or nucleic acid, e.g., an enzymatic, functional, physical, or chemical effect, such as the ability to decrease metastatic breast cancer or metastatic lung cancer. It includes ligand binding activity; cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis, and other characteristics of metastatic breast cancer or metastatic lung cancer cells. "Functional effects" include in vitro, in vivo, and ex vivo activities.
By "determining the functional effect" is meant assaying for a compound that increases or decreases a parameter that is indirectly or directly under the influence of a metastatic breast cancer or metastatic lung cancer protein sequence, e.g., functional, enzymatic, physical and chemical effects. Such functional effects can be measured by any means known to those skilled in the art, e.g., changes in spectroscopic characteristics (e.g., fluorescence, absorbance, refractive index), hydrodynamic (e.g., shape), chromatographic, or solubility properties for the protein, measuring inducible markers or transcriptional activation of the metastatic breast cancer or metastatic lung cancer protein; measuring binding activity or binding assays, e.g., binding to antibodies or other ligands, and measuring cellular proliferation. Determination of the functional effect of a compound on metastatic breast cancer or metastatic lung cancer can also be performed using metastatic breast cancer or • metastatic lung cancer assays known to those of skill in the art such as an in vitro assays, e.g., cell growth on soft agar; anchorage dependence; contact inhibition and density limitation of growth; cellular proliferation; cellular transformation; growth factor or serum dependence; tumor specific marker levels; invasiveness into Matrigel; tumor growth and metastasis in vivo; mRNA and protein expression in cells undergoing metastasis, and other characteristics of metastatic breast cancer or metastatic lung cancer cells. The functional effects can be evaluated by many means known to those skilled in the art, e.g., microscopy for quantitative or qualitative measures of alterations in morphological features, measurement of changes in RNA or protein levels for metastatic breast cancer or metastatic lung cancer-associated sequences, measurement of RNA stability, identification of downstream or reporter gene expression (CAT, luciferase, /3-gal, GFP and the like), e.g., via chemiluminescence, fluorescence, colorimetric reactions, antibody binding, inducible markers, and ligand binding assays.
"Inhibitors", "activators", and "modulators" of metastatic breast cancer or metastatic lung cancer polynucleotide and polypeptide sequences are used to refer to activating, inhibitory, or modulating molecules or compounds identified using in vitro and in vivo assays of metastatic breast cancer or metastatic lung cancer polynucleotide and polypeptide sequences of the invention. Inhibitors are compounds that, e.g., bind to, partially or totally block activity, decrease, prevent, delay activation, inactivate, desensitize, or down regulate the activity or expression of metastatic breast cancer or metastatic lung cancer proteins of the invention, e.g., antagonists. Antisense nucleic acids may seem to inhibit expression and subsequent function of the protein. "Activators" are compounds that increase, open, activate, facilitate, enhance activation, sensitize, agonize, or up regulate metastatic breast cancer or metastatic lung cancer protein activity. Inhibitors, activators, or modulators also include genetically modified versions of metastatic breast cancer or metastatic lung cancer proteins, e.g., versions with altered activity, as well as naturally occurring and synthetic ligands, antagonists, agonists, antibodies, small chemical molecules and the like. Such assays for inhibitors and activators include, e.g., expressing the metastatic breast cancer or metastatic lung cancer protein in vitro, in cells, or cell membranes, applying putative modulator compounds, and then determining the functional effects on activity, as described above. Activators and inhibitors of metastatic breast cancer or metastatic lung cancer can also be identified by incubating metastatic breast cancer or metastatic lung cancer cells with the test compound and determining increases or decreases in the expression of 1 or more metastatic breast cancer or metastatic lung cancer proteins, e.g., 1, 2, 3, 4, 5, 10, 15, 20, 25, 30, 40, 50 or more metastatic breast cancer or metastatic lung cancer proteins, such as metastatic breast cancer or metastatic lung cancer proteins encoded by the sequences set out in Tables 1-12.
Samples or assays comprising metastatic breast cancer or metastatic lung cancer proteins that are treated with a potential activator, inhibitor, or modulator are compared to control samples without the inhibitor, activator, or modulator to examine the extent of inhibition. Control samples (untreated with inhibitors) are assigned a relative protein activity value of 100%. Inhibition of a polypeptide is achieved when the activity value relative to the control is about 80%, preferably 50%), more preferably 25-0%). Activation of a metastatic breast cancer or metastatic lung cancer polypeptide is achieved when the activity value relative to the control (untreated with activators) is 110%, more preferably 150%), more preferably 200-500% (i.e., two to five fold higher relative to the control), more preferably 1000-3000% higher.
The phrase "changes in cell growth" refers to any change in cell growth and proliferation characteristics in vitro or in vivo, such as formation of foci, anchorage independence, semi-solid or soft agar growth, changes in contact inhibition and density limitation of growth, loss of growth factor or serum requirements, changes in cell morphology, gaining or losing immortalization, gaining or losing tumor specific markers, ability to form or suppress tumors when injected into suitable animal hosts, and/or immortalization of the cell. See, e.g., Freshney, Culture of Animal Cells a Manual of Basic Technique -pp. 231-241 (3rd ed. 1994).
"Tumor cell" refers to precancerous, cancerous, and normal cells in a tumor. "Cancer cells," "transformed" cells or "transformation" in tissue culture, refers to spontaneous or induced phenotypic changes that do not necessarily involve the uptake of new genetic material. Although transformation can arise from infection with a transforming virus and incorporation of new genomic DNA, or uptake of exogenous DNA, it can also arise spontaneously or following exposure to a carcinogen, thereby mutating an endogenous gene. Transformation is associated with phenotypic changes, such as immortalization of cells, aberrant growth control, nonmorphological changes, and/or malignancy (see, Freshney, Culture of Animal Cells a Manual of Basic Technique (3rd ed. 1994)).
"Antibody" refers to a polypeptide comprising a framework region from an immunoglobulin gene or fragments thereof that specifically binds and recognizes an antigen. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon, and mu constant region genes, as well as the myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in rum define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively. Typically, the antigen-binding region of an antibody or its functional equivalent will be most critical in specificity and affinity of binding. See Paul, Fundamental Immunology.
An exemplary immunoglobulin (antibody) structural unit comprises a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one "light" (about 25 kD) and one "heavy" chain (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (VL) and variable heavy chain (VH) refer to these light and heavy chains respectively.
Antibodies exist, e.g., as intact immunoglobulins or as a number of well- characterized fragments produced by digestion with various peptidases. Thus, e.g., pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab')2; a dimer of Fab which itself is a light chain joined to VH-CH1 by a disulfide bond. The F(ab')2 may be reduced under mild conditions to break the disulfide linkage in the hinge region, thereby converting the F(ab')'2 dimer into an Fab' monomer. The Fab' monomer is essentially Fab with part of the hinge region (see Fundamental Immunology (Paul ed., 3d ed. 1993). While various antibody fragments are defined in terms of the digestion of an intact antibody, one of skill will appreciate that such fragments may be synthesized de novo either chemically or by using recombinant DNA methodology. Thus, the term antibody, as used herein, also mcludes antibody fragments either produced by the modification of whole antibodies, or those synthesized de novo using recombinant DNA methodologies (e.g., single chain Fv) or those identified using phage display libraries (see, e.g., McCafferty et al, Nature 348:552-554 (1990))
For preparation of antibodies, e.g., recombinant, monoclonal, or polyclonal antibodies, many technique known in the art can be used (see, e.g., Kohler & Milstein, Nature 256:495-497 (1975); Kozbor et al, Immunology Today 4:72 (1983); Cole et al, pp. 77-96 in Monoclonal Antibodies and Cancer Therapy (1985); Coligan, Current Protocols in Immunology (1991); Harlow & Lane, Antibodies, A Laboratory Manual (1988); and Goding, Monoclonal Antibodies: Principles and Practice (2d ed. 1986)). Techniques for the production of single chain antibodies (U.S. Patent 4,946,778) can be adapted to produce antibodies to polypeptides of this invention. Also, transgenic mice, or other organisms such as other mammals, may be used to express humanized antibodies. Alternatively, phage display technology can be used to identify antibodies and heteromeric Fab fragments that specifically bind to selected antigens (see, e.g., McCafferty et al, Nature 348:552-554 (1990); Marks et al, Biotechnology 10:779-783 (1992)).
A "chimeric antibody" is an antibody molecule in which, e.g, (a) the constant region, or a portion thereof, is altered, replaced or exchanged so that the antigen binding site (variable region) is linked to a constant region of a different or altered class, effector function and/or species, or an entirely different molecule which confers new properties to the chimeric antibody, e.g., an enzyme, toxin, hormone, growth factor, drug, etc.; or (b) the variable region, or a portion thereof, is altered, replaced or exchanged with a variable region having a different or altered antigen specificity.
Identification of metastatic breast cancer or metastatic lung cancer-associated sequences
In one aspect, the expression levels of genes are determined in different patient samples for which diagnosis information is desired, to provide expression profiles. An expression profile of a particular sample is essentially a "fingerprint" of the state of the sample; while two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is characteristic of the state of the cell. That is, normal tissue may be distinguished from cancerous or metastatic cancerous tissue, or metastatic cancerous tissue can be compared with tissue from surviving cancer patients. By comparing expression profiles of tissue in known different metastatic breast cancer or metastatic lung cancer states, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained.
The identification of sequences that are differentially expressed in metastatic breast cancer or metastatic lung cancer versus non-metastatic breast cancer or non- metastatic lung cancer tissue allows the use of this information in a number of ways. For example, a particular treatment regime may be evaluated: does a chemotherapeutic drag act to down- regulate metastatic breast cancer or metastatic lung cancer, and thus tumor growth or recurrence, in a particular patient. Similarly, diagnosis and treatment outcomes may be done or confirmed by comparing patient samples with the known expression profiles. Metastatic tissue can also be analyzed to determine the stage of metastatic breast cancer or metastatic lung cancer in the tissue. Furthermore, these gene expression profiles (or individual genes) allow screening of drug candidates with an eye to mimicking or altering a particular expression profile; e.g., screening can be done for drugs that suppress the metastatic breast cancer or metastatic lung cancer expression profile. This may be done by making biochips comprising sets of the important metastatic breast cancer or metastatic lung cancer genes, which can then be used in these screens. PCR methods may be applied with selected primer pairs, and analysis may be of RNA or of genomic sequences. These methods can also be done on the protein basis; that is, protein expression levels of the metastatic breast cancer or metastatic lung cancer proteins can be evaluated for diagnostic purposes or to screen candidate agents. In addition, the metastatic breast cancer or metastatic lung cancer nucleic acid sequences can be administered for gene therapy purposes, including the administration of antisense nucleic acids, or the metastatic breast cancer or metastatic lung cancer proteins (including antibodies and other modulators thereof) administered as therapeutic drugs or as protein or DNA vaccines. Thus the present invention provides nucleic acid and protein sequences that are differentially expressed in metastatic breast cancer or metastatic lung cancer, herein termed "metastatic breast cancer or metastatic lung cancer sequences." As outlined below, metastatic breast cancer or metastatic lung cancer sequences include those that are upregulated (i.e., expressed at a higher level) in metastatic breast cancer or metastatic lung cancer, as well as those that are down-regulated (i.e., expressed at a lower level). In a preferred embodiment, the metastatic breast cancer or metastatic lung cancer sequences are from humans; however, as will be appreciated by those in the art, metastatic breast cancer or metastatic lung cancer sequences from other organisms may be useful in animal models of disease and drug evaluation; thus, other metastatic breast cancer or metastatic lung cancer sequences are provided, from vertebrates, including mammals, including rodents (rats, mice, hamsters, guinea pigs, etc.), primates, farm animals (including sheep, goats, pigs, cows, horses, etc.) and pets (dogs, cats, etc.). Metastatic breast cancer or metastatic lung cancer sequences from other organisms may be obtained using the techniques outlined below. Metastatic breast cancer or metastatic lung cancer sequences can include both nucleic acid and amino acid sequences. As will be appreciated by those in the art and is more fully outlined below, metastatic breast cancer or metastatic lung cancer nucleic acid sequences are useful in a variety of applications, including diagnostic applications, which will detect naturally occurring nucleic acids, as well as screening applications; e.g., biochips comprising nucleic acid probes or PCR microtiter plates with selected probes to the metastatic breast cancer or metastatic lung cancer sequences can be generated.
A metastatic breast cancer or metastatic lung cancer sequence can be initially identified by substantial nucleic acid and/or amino acid sequence homology to the metastatic breast cancer or metastatic lung cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions.
For identifying metastatic breast cancer or metastatic lung cancer-associated sequences, the metastatic breast cancer or metastatic lung cancer screen typically mcludes comparing genes identified in different tissues, e.g., normal and cancerous tissues, or tumor tissue samples from patients who have metastatic disease vs. non metastatic tissue, or tumor tissue samples from patients who have been diagnosed cancer but have survived vs. metastatic tissue. Other suitable tissue comparisons include comparing metastatic breast cancer or metastatic lung cancer samples with metastatic cancer samples from other cancers, such as gastrointestinal cancers, prostate, ovarian, etc. Samples of, e.g., breast cancer survivor tissue and tissue undergoing metastasis are applied to biochips comprising nucleic acid probes. The samples are first microdissected, if applicable, and treated as is known in the art for the preparation of mRNA. Suitable biochips are commercially available, e.g., GENECHIP® (DNA microarray) technology from Affymetrix, Inc. (Santa Clara, CA). Gene expression profiles as described herein are generated and the data analyzed.
In one embodiment, the genes showing changes in expression as between normal and disease states are compared to genes expressed in other normal tissues, preferably normal colon, but also including, and not limited to lung, heart, brain, liver, breast, kidney, muscle, prostate, small intestine, large intestine, spleen, bone and placenta. In a preferred embodiment, those genes identified during the metastatic breast cancer or metastatic lung cancer screen that are expressed in significant amounts in other tissues are removed from the profile, although in some embodiments, this is not necessary. That is, when screening for drags, it is usually preferable that the target be disease specific, to minimize possible side effects. In a preferred embodiment, metastatic breast cancer or metastatic lung cancer sequences are those that are up-regulated in metastatic breast cancer or metastatic lung cancer; that is, the expression of these genes is higher in the metastatic tissue as compared to non-metastatic cancerous tissue or normal tissue (see, e.g., Tables 1-3, 6-8, 11-12). "Up- regulation" as used herein means, when the ratio is presented as a number greater than one, that the ratio is greater than one, preferably 1.5 or greater, more preferably 2.0 or greater. All UniGene cluster identification numbers and accession numbers herein are for the GenBank sequence database and the sequences of the accession numbers are hereby expressly incorporated by reference. GenBank is known in the art, see, e.g., Benson, DA, et al, Nucleic Acids Research 26: 1-7 (1998) and. Sequences are also available in other databases, e.g., European Molecular Biology Laboratory (EMBL) and DNA Database of Japan (DDBJ). In another preferred embodiment, metastatic breast cancer or metastatic lung cancer sequences are those that are down-regulated in the metastatic breast cancer or metastatic lung cancer; that is, the expression of these genes is lower in metastatic tissue as compared to non- metastatic cancerous tissue or normal tissue (see, e.g., Tables 4-5 and 9-10). "Down- regulation" as used herein means, when the ratio is presented as a number greater than one, that the ratio is greater than one, preferably 1.5 or greater, more preferably 2.0 or greater, or, when the ratio is presented as a number less than one, that the ratio is less than one, preferably 0.5 or less, more preferably 0.25 or less.
Informatics
The ability to identify genes that are over or under expressed in metastatic breast cancer or metastatic lung cancer can additionally provide high-resolution, high-sensitivity datasets which can be used in the areas of diagnostics, therapeutics, drag development, pharmacogenetics, protein stracture, biosensor development, and other related areas. For example, the expression profiles can be used in diagnostic or prognostic evaluation of patients with metastatic breast cancer or metastatic lung cancer. Or as another example, subcellular toxicological information can be generated to better direct drag stracture and activity correlation (see Anderson, Pharmaceutical Proteomics: Targets, Mechanism, and Function, paper presented at the IBC Proteomics conference, Coronado, CA (June 11-12, 1998)). Subcellular toxicological information can also be utilized in a biological sensor device to predict the likely toxicological effect of chemical exposures and likely tolerable exposure thresholds (see U.S. Patent No. 5,811,231). Similar advantages accrue from datasets relevant to other biomolecules and bioactive agents (e.g., nucleic acids, saccharides, lipids, drags, and the like).
Thus, in another embodiment, the present invention provides a database that includes at least one set of assay data. The data contained in the database is acquired, e.g., using array analysis either singly or in a library format. The database can be in substantially any form in which data can be maintained and transmitted, but is preferably an electronic database. The electronic database of the invention can be maintained on any electronic device allowing for the storage of and access to the database, such as a personal computer, but is preferably distributed on a wide area network, such as the World Wide Web.
The focus of the present section on databases that include peptide sequence data is for clarity of illustration only. It will be apparent to those of skill in the art that similar databases can be assembled for assay data acquired using an assay of the invention.
The compositions and methods for identifying and/or quantitating the relative and/or absolute abundance of a variety of molecular and macromolecular species from a biological sample undergoing metastatic breast cancer or metastatic lung cancer, i.e., the identification of metastatic breast cancer or metastatic lung cancer-associated sequences described herein, provide an abundance of information, which can be correlated with pathological conditions, predisposition to disease, drag testing, therapeutic monitoring, gene- disease causal linkages, identification of correlates of immunity and physiological status, among others. Although the data generated from the assays of the invention is suited for manual review and analysis, in a preferred embodiment, prior data processing using highspeed computers is utilized.
An array of methods for indexing and retrieving biomolecular information is known in the art. For example, U.S. Patents 6,023,659 and 5,966,712 disclose a relational database system for storing biomolecular sequence information in a manner that allows sequences to be catalogued and searched according to one or more protein function hierarchies. U.S. Patent 5,953,727 discloses a relational database having sequence records containing information in a format that allows a collection of partial-length DNA sequences to be catalogued and searched according to association with one or more sequencing projects for obtaining full-length sequences from the collection of partial length sequences. U.S. Patent 5,706,498 discloses a gene database retrieval system for making a retrieval of a gene sequence similar to a sequence data item in a gene database based on the degree of similarity between a key sequence and a target sequence. U.S. Patent 5,538,897 discloses a method using mass spectroscopy fragmentation patterns of peptides to identify amino acid sequences in computer databases by comparison of predicted mass spectra with experimentally-derived mass spectra using a closeness-of-fit measure. U.S. Patent 5,926,818 discloses a multidimensional database comprising a functionality for multi-dimensional data analysis described as on-line analytical processing (OLAP), which entails the consolidation of projected and actual data according to more than one consolidation path or dimension. U.S. Patent 5,295,261 reports a hybrid database structure in which the fields of each database record are divided into two classes, navigational and informational data, with navigational fields stored in a hierarchical topological map which can be viewed as a tree structure or as the merger of two or more such tree structures.
See also Mount et al, Bioinformatics (2001); Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids (Durbin et al, eds., 1999);
Bioinformatics: A Practical Guide to the Analysis of Genes and Proteins (Baxevanis & Oeullette eds., 1998)); Rashidi & Buehler, Bioinformatics: Basic Applications in Biological Science and Medicine (1999); Introduction to Computational Molecular Biology (Setubal et al., eds 1997); Bioinformatics: Methods and Protocols (Misener & Krawetz, eds, 2000); Bioinformatics: Sequence, Structure, and Databanks: A Practical Approach (Higgins & Taylor, eds., 2000); Brown, Bioinformatics: A Biologist's Guide to Biocomputing and the Internet (2001); Han & Kamber, Data Mining: Concepts and Techniques (2000); and Waterman, Introduction to Computational Biology: Maps, Sequences, and Genomes (1995). The present invention provides a computer database comprising a computer and software for storing in computer-retrievable form assay data records cross-tabulated, e.g., with data specifying the source of the target-containing sample from which each sequence specificity record was obtained.
In an exemplary embodiment, at least one of the sources of target-containing sample is from a control tissue sample known to be free of pathological disorders. In a variation, at least one of the sources is a known pathological tissue specimen, e.g., a neoplastic lesion or another tissue specimen to be analyzed for metastatic breast cancer or metastatic lung cancer. In another variation, the assay records cross-tabulate one or more of the following parameters for each target species in a sample: (1) a unique identification code, which can include, e.g., a target molecular stracture and/or characteristic separation coordinate (e.g., electrophoretic coordinates); (2) sample source; and (3) absolute and/or relative quantity of the target species present in the sample.
The invention also provides for the storage and retrieval of a collection of target data in a computer data storage apparatus, which can include magnetic disks, optical disks, magneto-optical disks, DRAM, SRAM, SGRAM, SDRAM, RDRAM, DDR RAM, magnetic bubble memory devices, and other data storage devices, including CPU registers and on-CPU data storage arrays. Typically, the target data records are stored as a bit pattern in an array of magnetic domains on a magnetizable medium or as an array of charge states or transistor gate states, such as an array of cells in a DRAM device (e.g., each cell comprised of a transistor and a charge storage area, which may be on the transistor). In one embodiment, the invention provides such storage devices, and computer systems built therewith, comprising a bit pattern encoding a protein expression fingerprint record comprising unique identifiers for at least 10 target data records cross-tabulated with target source.
When the target is a peptide or nucleic acid, the invention preferably provides a method for identifying related peptide or nucleic acid sequences, comprising performing a computerized comparison between a peptide or nucleic acid sequence assay record stored in or retrieved from a computer storage device or database and at least one other sequence. The comparison can include a sequence analysis or comparison algorithm or computer program embodiment thereof (e.g., FASTA, TFASTA, GAP, BESTFIT) and/or the comparison may be of the relative amount of a peptide or nucleic acid sequence in a pool of sequences determined from a polypeptide or nucleic acid sample of a specimen.
The invention also preferably provides a magnetic disk, such as an IBM-compatible (DOS, Windows, Windows95/98/2000, Windows NT, OS/2) or other format (e.g., Linux, SunOS, Solaris, ATX, SCO Unix, VMS, MV, Macintosh, etc.) floppy diskette or hard (fixed, Winchester) disk drive, comprising a bit pattern encoding data from an assay of the invention in a file format suitable for retrieval and processing in a computerized sequence analysis, comparison, or relative quantitation method.
The invention also provides a network, comprising a plurality of computing devices linked via a data link, such as an Ethernet cable (coax or lOBaseT), telephone line, ISDN line, wireless network, optical fiber, or other suitable signal transmission medium, whereby at least one network device (e.g., computer, disk array, etc.) comprises a pattern of magnetic domains (e.g., magnetic disk) and or charge domains (e.g., an array of DRAM cells) composing a bit pattern encoding data acquired from an assay of the invention.
The invention also provides a method for transmitting assay data that mcludes generating an electronic signal on an electronic communications device, such as a modem, ISDN terminal adapter, DSL, cable modem, ATM switch, or the like, wherein the signal includes (in native or encrypted format) a bit pattern encoding data from an assay or a database comprising a plurality of assay results obtained by the method of the invention.
In a preferred embodiment, the invention provides a computer system for comparing a query target to a database containing an array of data structures, such as an assay result obtained by the method of the invention, and ranking database targets based on the degree of identity and gap weight to the target data. A central processor is preferably initialized to load and execute the computer program for alignment and/or comparison of the assay results. Data for a query target is entered into the central processor via an I/O device. Execution of the computer program results in the central processor retrieving the assay data from the data file, which comprises a binary description of an assay result.
The target data or record and the computer program can be transferred to secondary memory, which is typically random access memory (e.g., DRAM, SRAM, SGRAM, or SDRAM). Targets are ranked according to the degree of correspondence between a selected assay characteristic (e.g., binding to a selected affinity moiety) and the same characteristic of the query target and results are output via an I/O device. For example, a central processor can be a conventional computer (e.g., Intel Pentium, PowerPC, Alpha, PA-8000, SPARC, MIPS 4400, MIPS 10000, VAX, etc.); a program can be a commercial or public domain molecular biology software package (e.g., UWGCG Sequence Analysis Software, Darwin); a data file can be an optical or magnetic disk, a data server, a memory device (e.g., DRAM, SRAM, SGRAM, SDRAM, EPROM, bubble memory, flash memory, etc.); an I O device can be a terminal comprising a video display and a keyboard, a modem, an ISDN terminal adapter, an Ethernet port, a punched card reader, a magnetic strip reader, or other suitable I/O device.
The invention also preferably provides the use of a computer system, such as that described above, which comprises: (1) a computer; (2) a stored bit pattern encoding a collection of peptide sequence specificity records obtained by the methods of the invention, which may be stored in the computer; (3) a comparison target, such as a query target; and (4) a program for alignment and comparison, typically with rank-ordering of comparison results on the basis of computed similarity values.
Characteristics of metastatic breast cancer or metastatic lung cancer-associated proteins Metastatic breast cancer or metastatic lung cancer proteins of the present invention may be classified as secreted proteins, transmembrane proteins or intracellular proteins. In one embodiment, the metastatic breast cancer or metastatic lung cancer protein is an intracellular protein. Intracellular proteins may be found in the cytoplasm and/or in the nucleus and/or in the organelles. Proteins containing one or more transmembrane domains that exclusively reside in organelles are also considered intracellular proteins. Intracellular proteins are involved in all aspects of cellular function and replication (including, e.g., signaling pathways); aberrant expression of such proteins often results in unregulated or disregulated cellular processes (see, e.g., Molecular Biology of the Cell (Alberts, ed., 3rd ed., 1994). For example, many intracellular proteins have enzymatic activity such as protein kinase activity, protein phosphatase activity, protease activity, nucleotide cyclase activity, polymerase activity and the like. Intracellular proteins also serve as docking proteins that are involved in organizing complexes of proteins, or targeting proteins to various subcellular localizations, and are involved in maintaining the structural integrity of organelles. An increasingly appreciated concept in characterizing proteins is the presence in the proteins of one or more motifs for which defined functions have been attributed. In addition to the highly conserved sequences found in the enzymatic domain of proteins, highly conserved sequences have been identified in proteins that are involved in protein-protein interaction. For example, Src-homology-2 (SH2) domains bind tyrosine-phosphorylated targets in a sequence dependent manner. PTB domains, which are distinct from SH2 domains, also bind tyrosine phosphorylated targets. SH3 domains bind to proline-rich targets. In addition, PH domains, tetratricopeptide repeats and WD domains to name only a few, have been shown to mediate protein-protein interactions. Some of these may also be involved in binding to phospholipids or other second messengers. As will be appreciated by one of ordinary skill in the art, these motifs can be identified on the basis of primary sequence; thus, an analysis of the sequence of proteins may provide insight into both the enzymatic potential of the molecule and/or molecules with which the protein may associate. One useful database is Pfam (protein families), which is a large collection of multiple sequence alignments and hidden Markov models covering many common protein domains. Versions are available via the internet from Washington University in St. Louis, the Sanger Center in England, and the Karolinska Institute in Sweden (see, e.g., Bateman et al, Nuc. Acids Res. 28:263-266 (2000); Sonnhammer et al, Proteins 28:405-420 (1997); Bateman et al, Nuc. Acids Res. 27:260-262 (1999); and Sonnhammer et al, Nuc. Acids Res. 26:320-322- (1998)). In another embodiment, the metastatic breast cancer or metastatic lung cancer sequences are transmembrane proteins. Transmembrane proteins are molecules that span a phospholipid bilayer of a cell. They may have an intracellular domain, an extracellular domain, or both. The intracellular domains of such proteins may have a number of functions including those already described for intracellular proteins. For example, the intracellular domain may have enzymatic activity and/or may serve as a binding site for additional proteins. Frequently the intracellular domain of transmembrane proteins serves both roles. For example certain receptor tyrosine kinases have both protein kinase activity and SH2 domains. In addition, autophosphorylation of tyrosines on the receptor molecule itself, creates binding sites for additional SH2 domain containing proteins. Transmembrane proteins may contain from one to many transmembrane domains. For example, receptor tyrosine kinases, certain cytokine receptors, receptor guanylyl cyclases and receptor serine/tlireonme protein kinases contain a single transmembrane domain. However, various other proteins including channels, pumps, and adenylyl cyclases contain numerous transmembrane domains. Many important cell surface receptors such as G protem coupled receptors (GPCRs) are classified as "seven transmembrane domain" proteins, as they contain 7 membrane spanning regions. Characteristics of transmembrane domains include approximately 20 consecutive hydrophobic amino acids that may be followed by charged amino acids. Therefore, upon analysis of the amino acid sequence of a particular protein, the localization and number of transmembrane domains within the protein may be predicted (see, e.g. PSORT web site).
The extracellular domains of transmembrane proteins are diverse; however, conserved motifs are found repeatedly among various extracellular domains. Conserved structure and/or functions have been ascribed to different extracellular motifs. Many extracellular domains are involved in binding to other molecules. In one aspect, extracellular domains are found on receptors. Factors that bind the receptor domain include circulating ligands, which may be peptides, proteins, or small molecules such as adenosine and the like. For example, growth factors such as EGF, FGF and PDGF are circulating growth factors that bind to their cognate receptors to initiate a variety of cellular responses. Other factors include cytokines, mitogenic factors, hormones, neurotrophic factors and the like. Extracellular domains also bind to cell-associated molecules, hi this respect, they mediate cell-cell interactions. Cell-associated ligands can be tethered to the cell, e.g., via a glycosylphosphatidylinositol (GPI) anchor, or may themselves be transmembrane proteins. Extracellular domains also associate with the extracellular matrix and contribute to the maintenance of the cell structure.
Metastatic breast cancer or metastatic lung cancer proteins that are transmembrane are particularly preferred in the present invention as they are readily accessible targets for extracellular immunotherapeutics, as are described herein. In addition, as outlined below, transmembrane proteins can be also useful in imaging modalities. Antibodies may be used to label such readily accessible proteins in situ or in histological analysis. Alternatively, antibodies can also label intracellular proteins, in which case analytical samples are typically permeablized to provide access to intracellular proteins.
It will also be appreciated by those in the art that a transmembrane protein can be made soluble by removing transmembrane sequences, e.g., tlirough recombinant methods. Furthermore, transmembrane proteins that have been made soluble can be made to be secreted through recombinant means by adding an appropriate signal sequence.
In another embodiment, the metastatic breast cancer or metastatic lung cancer proteins are secreted proteins; the secretion of which can be either constitutive or regulated. These proteins have a signal peptide or signal sequence that targets the molecule to the secretory pathway. Secreted proteins are involved in numerous physiological events; by virtue of their circulating nature, they often serve to transmit signals to various other cell types. The secreted protein may function in an autocrine manner (acting on the cell that secreted the factor), a paracrine manner (acting on cells in close proximity to the cell that secreted the factor) or an endocrine manner (acting on cells at a distance). Thus secreted molecules find use in modulating or altering numerous aspects of physiology. Metastatic breast cancer or metastatic lung cancer proteins that are secreted proteins are particularly preferred in the present invention as they serve as good targets for diagnostic markers, e.g., for blood, plasma, serum, or stool tests.
Use of metastatic breast cancer or metastatic lung cancer nucleic acids
As described above, metastatic breast cancer or metastatic lung cancer sequence is initially identified by substantial nucleic acid and/or amino acid sequence homology or linkage to the metastatic breast cancer or metastatic lung cancer sequences outlined herein. Such homology can be based upon the overall nucleic acid or amino acid sequence, and is generally determined as outlined below, using either homology programs or hybridization conditions. Typically, linked sequences on a mRNA are found on the same molecule.
The metastatic breast cancer or metastatic lung cancer nucleic acid sequences of the invention, e.g., the sequences in Tables 1-12, can be fragments of larger genes, i.e., they are nucleic acid segments. "Genes" in this context includes coding regions, non-coding regions, and mixtures of coding and non-coding regions. Accordingly, as will be appreciated by those in the art, using the sequences provided herein, extended sequences, in either direction, of the metastatic breast cancer or metastatic lung cancer genes can be obtained, using techniques well known in the art for cloning either longer sequences or the full length sequences; see Ausubel, et al, supra. Much can be done by informatics and many sequences can be clustered to include multiple sequences corresponding to a single gene, e.g., systems such as UniGene.
Once the metastatic breast cancer or metastatic lung cancer nucleic acid is identified, it can be cloned and, if necessary, its constituent parts recombined to form the entire metastatic breast cancer or metastatic lung cancer nucleic acid coding regions or the entire mRNA sequence. Once isolated from its natural source, e.g., contained within a plasmid or other vector or excised therefrom as a linear nucleic acid segment, the recombinant metastatic breast cancer or metastatic lung cancer nucleic acid can be further- used as a probe to identify and isolate other metastatic breast cancer or metastatic lung cancer nucleic acids, e.g., extended coding regions. It can also be used as a "precursor" nucleic acid to make modified or variant metastatic breast cancer or metastatic lung cancer nucleic acids and proteins.
The metastatic breast cancer or metastatic lung cancer nucleic acids of the present invention are used in several ways. In a first embodiment, nucleic acid probes to the metastatic breast cancer or metastatic lung cancer nucleic acids are made and attached to biochips to be used in screening and diagnostic methods, as outlined below, or for administration, e.g., for gene therapy, vaccine, and/or antisense applications. Alternatively, the metastatic breast cancer or metastatic lung cancer nucleic acids that include coding regions of metastatic breast cancer or metastatic lung cancer proteins can be put into expression vectors for the expression of metastatic breast cancer or metastatic lung cancer proteins, again for screening purposes or for administration to a patient.
In a preferred embodiment, nucleic acid probes to metastatic breast cancer or metastatic lung cancer nucleic acids (both the nucleic acid sequences outlined in the figures and/or the complements thereof) are made. The nucleic acid probes attached to the biochip are designed to be substantially complementary to the metastatic breast cancer or metastatic lung cancer nucleic acids, i.e. the target sequence (either the target sequence of the sample or to other probe sequences, e.g., in sandwich assays), such that hybridization of the target sequence and the probes of the present invention occurs. As outlined below, this complementarity need not be perfect; there may be any number of base pair mismatches which will interfere with hybridization between the target sequence and the single stranded nucleic acids of the present invention. However, if the number of mutations is so great that no hybridization can occur under even the least stringent of hybridization conditions, the sequence is not a complementary target sequence. Thus, by "substantially complementary" herein is meant that the probes are sufficiently complementary to the target sequences to hybridize under appropriate reaction conditions, particularly high stringency conditions, as outlined herein.
A nucleic acid probe is generally single stranded but can be partially single and partially double stranded. The strandedness of the probe is dictated by the stracture, composition, and properties of the target sequence. In general, the nucleic acid probes range from about 8 to about 100 bases long, with from about 10 to about 80 bases being preferred, and from about 30 to about 50 bases being particularly preferred. That is, generally complements of ORFs or whole genes are not used. In some embodiments, nucleic acids of lengths up to hundreds of bases can be used.
In a preferred embodiment, more than one probe per sequence is used, with either overlapping probes or probes to different sections of the target being used. That is, two, three, four or more probes, with three being preferred, are used to build in a redundancy for a particular target. The probes can be overlapping (i.e., have some sequence in common), or separate. In some cases, PCR primers may be used to amplify signal for higher sensitivity. As will be appreciated by those in the art, nucleic acids can be attached or immobilized to a solid support in a wide variety of ways. By "immobilized" and grammatical equivalents herein is meant the association or binding between the nucleic acid probe and the solid support is sufficient to be stable under the conditions of binding, washing, analysis, and removal as outlined below. The binding can typically be covalent or non-covalent. By "non- covalent binding" and grammatical equivalents herein is typically meant one or more of electrostatic, hydrophilic, and hydrophobic interactions. Included in non-covalent binding is the covalent attachment of a molecule, such as, streptavidin to the support and the non- covalent binding of the biotinylated probe to the streptavidin. By "covalent binding" and grammatical equivalents herein is meant that the two moieties, the solid support and the probe, are attached by at least one bond, including sigma bonds, pi bonds and coordination bonds. Covalent bonds can be formed directly between the probe and the solid support or can be formed by a cross linker or by inclusion of a specific reactive group on either the solid support or the probe or both molecules. Immobilization may also involve a combination of covalent and non-covalent interactions.
In general, the probes are attached to a biochip in a wide variety of ways, as will be appreciated by those in the art. As described herein, the nucleic acids can either be synthesized first, with subsequent attachment to the biochip, or can be directly synthesized on the biochip. The biochip comprises a suitable solid substrate. By "substrate" or "solid support" or other grammatical equivalents herein is meant a material that can be modified to contain discrete individual sites appropriate for the attachment or association of the nucleic acid probes and is amenable to at least one detection method. As will be appreciated by those in the art, the number of possible substrates are very large, and include, but are not limited to, glass and modified or fiinctionalized glass, plastics (including acrylics, polystyrene and copolymers of styrene and other materials, polypropylene, polyethylene, polybutylene, polyurethanes, Teflon, etc.), polysaccharides, nylon or nitrocellulose, resins, silica or silica- based materials including silicon and modified silicon, carbon, metals, inorganic glasses, plastics, etc. In general, the substrates allow optical detection and do not appreciably fluoresce. A preferred substrate is described in copending application entitled Reusable Low Fluorescent Plastic Biochip, U.S. Application Serial No. 09/270,214, filed March 15, 1999, herein incorporated by reference in its entirety.
Generally the substrate is planar, although as will be appreciated by those in the art, other configurations of substrates may be used as well. For example, the probes may be placed on the inside surface of a tube, for flow-through sample analysis to minimize sample volume. Similarly, the substrate may be flexible, such as a flexible foam, including closed cell foams made of particular plastics.
In a preferred embodiment, the surface of the biochip and the probe may be derivatized with chemical functional groups for subsequent attachment of the two. Thus, e.g., the biochip is derivatized with a chemical functional group including, but not limited to, amino groups, carboxy groups, oxo groups and thiol groups, with amino groups being particularly preferred. Using these functional groups, the probes can be attached using functional groups on the probes. For example, nucleic acids containing amino groups can be attached to surfaces comprising amino groups, e.g., using linkers as are known in the art; e.g., homo-or hetero-bifunctional linkers as are well known (see 1994 Pierce Chemical Company catalog, technical section on cross-linkers, pages 155-200). In addition, in some cases, additional linkers, such as alkyl groups (including substituted and heteroalkyl groups) may be used. In this embodiment, oligonucleotides are synthesized as is known in the art, and then attached to the surface of the solid support. As will be appreciated by those skilled in the art, either the 5 ' or 3 ' terminus may be attached to the solid support, or attachment may be via an internal nucleoside.
In another embodiment, the immobilization to the solid support may be very strong, yet non-covalent. For example, biotinylated oligonucleotides can be made, which bind to surfaces covalently coated with streptavidin, resulting in attachment.
Alternatively, the oligonucleotides may be synthesized on the surface, as is known in the art. For example, photoactivation techniques utilizing photopolymerization compounds and techniques are used. In a preferred embodiment, the nucleic acids can be synthesized in situ, using well known photolithographic techniques, such as those described in WO 95/25116; WO 95/35505; U.S. Patent Nos. 5,700,637 and 5,445,934; and references cited within, all of which are expressly incorporated by reference; these methods of attachment form the basis of the GENECHIP® (DNA microarray) technology from Affymetrix, Inc. (Santa Clara, CA).
Often, amplification-based assays are performed to measure the expression level of metastatic breast cancer or metastatic lung cancer-associated sequences. These assays are typically performed in conjunction with reverse transcription. In such assays, a metastatic breast cancer or metastatic lung cancer-associated nucleic acid sequence acts as a template in an amplification reaction (e.g., Polymerase Chain Reaction, or PCR). In a quantitative amplification, the amount of amplification product will be proportional to the amount of template in the original sample. Comparison to appropriate controls provides a measure of the amount of metastatic breast cancer or metastatic lung cancer-associated RNA. Methods of quantitative amplification are well known to those of skill in the art. Detailed protocols for quantitative PCR are provided, e.g., in Innis et al. , PCR Protocols, A Guide to Methods and Applications (1990).
In some embodiments, a TAQMAN® (PCR reagent kit) based assay is used to measure expression. TAQMAN® (PCR reagent kit) based assays use a fluorogenic oligonucleotide probe that contains a 5' fluorescent dye and a 3' quenching agent. The probe hybridizes to a PCR product, but cannot itself be extended due to a blocking agent at the 3 ' end. When the PCR product is amplified in subsequent cycles, the 5' nuclease activity of the polymerase, e.g., AMPLITAQ® (PCR enzyme reagent) , results in the cleavage of the TAQMAN® (PCR reagent kit) probe. This cleavage separates the 5' fluorescent dye and the 3' quenching agent, thereby resulting in an increase in fluorescence as a function of amplification (see, e.g. , literature provided by Perkin-Elmer, e.g., www2.perkin-elmer.com). Other suitable amplification methods include, but are not limited to, ligase chain reaction (LCR) (see Wu & Wallace, Genomics 4:560 (1989), Landegren et al, Science 241:1077 (1988), and Barringer et al, Gene 89:117 (1990)), transcription amplification (Kwoh et al, Proc. Natl Acad. Sci. USA 86: 1173 (1989)), self-sustained sequence replication (Guatelli et al, Proc. Nat. Acad. Sci. USA 87:1874 (1990)), dot PCR, and linker adapter PCR, etc. Expression of metastatic breast cancer or metastatic lung cancer proteins from nucleic acids
In a preferred embodiment, metastatic breast cancer or metastatic lung cancer nucleic acids, e.g., encoding metastatic breast cancer or metastatic lung cancer proteins, are used to make a variety of expression vectors to express metastatic breast cancer or metastatic lung cancer proteins which can then be used in screening assays, as described below. Expression vectors and recombinant DNA technology are well known to those of skill in the art (see, e.g., Ausubel, supra, and Gene Expression Systems (Fernandez & Hoeffler, eds, 1999)) and are used to express proteins. The expression vectors may be either self- replicating extrachromosomal vectors or vectors which integrate into a host genome. Generally, these expression vectors include transcriptional and translational regulatory nucleic acid operably linked to the nucleic acid encoding the metastatic breast cancer or metastatic lung cancer protein. The term "control sequences" refers to DNA sequences used for the expression of an operably linked coding sequence in a particular host organism. Control sequences that are suitable for prokaryotes, e.g., include a promoter, optionally an operator sequence, and a ribosome binding site. Eukaryotic cells are known to utilize promoters, polyadenylation signals, and enhancers.
Nucleic acid is "operably linked" when it is placed into a functional relationship with another nucleic acid sequence. For example, DNA for a presequence or secretory leader is operably linked to DNA for a polypeptide if it is expressed as a preprotein that participates in the secretion of the polypeptide; a promoter or enhancer is operably linked to a coding sequence if it affects the transcription of the sequence; or a ribosome binding site is operably linked to a coding sequence if it is positioned so as to facilitate translation. Generally, "operably linked" means that the DNA sequences being linked are contiguous, and, in the case of a secretory leader, contiguous and in reading phase. However, enhancers do not have to be contiguous. Linking is typically accomplished by ligation at convenient restriction sites. If such sites do not exist, synthetic oligonucleotide adaptors or linkers are used in accordance with conventional practice. Transcriptional and translational regulatory nucleic acid will generally be appropriate to the host cell used to express the metastatic breast cancer or metastatic lung cancer protein. Numerous types of appropriate expression vectors, and suitable regulatory sequences are known in the art for a variety of host cells.
In general, transcriptional and translational regulatory sequences may include, but are not limited to, promoter sequences, ribosomal binding sites, transcriptional start and stop sequences, translational start and stop sequences, and enhancer or activator sequences. In a preferred embodiment, the regulatory sequences include a promoter and transcriptional start and stop sequences.
Promoter sequences encode either constitutive or inducible promoters. The promoters may be either naturally occurring promoters or hybrid promoters. Hybrid promoters, which combine elements of more than one promoter, are also known in the art, and are useful in the present invention.
In addition, an expression vector may comprise additional elements. For example, the expression vector may have two replication systems, thus allowing it to be maintained in two organisms, e.g., in mammalian or insect cells for expression and in a procaryotic host for cloning and amplification. Furthermore, for integrating expression vectors, the expression vector contains at least one sequence homologous to the host cell genome, and preferably two homologous sequences which flank the expression construct. The integrating vector may be directed to a specific locus in the host cell by selecting the appropriate homologous sequence for inclusion in the vector. Constructs for integrating vectors are well known in the art (e.g., Fernandez & Hoeffler, supra).
In addition, in a preferred embodiment, the expression vector contains a selectable marker gene to allow the selection of transformed host cells. Selection genes are well known in the art and will vary with the host cell used.
The metastatic breast cancer or metastatic lung cancer proteins of the present invention are produced by culturmg a host cell transformed with an expression vector containing nucleic acid encoding a metastatic breast cancer or metastatic lung cancer protein, under the appropriate conditions to induce or cause expression of the metastatic breast cancer or metastatic lung cancer protein. Conditions appropriate for metastatic breast cancer or metastatic lung cancer protein expression will vary with the choice of the expression vector and the host cell, and will be easily ascertained by one skilled in the art through routine experimentation or optimization. For example, the use of constitutive promoters in the expression vector will require optimizing the growth and proliferation of the host cell, while the use of an inducible promoter requires the appropriate growth conditions for induction. In addition, in some embodiments, the timing of the harvest is important. For example, the baculoviral systems used in insect cell expression are lytic viruses, and thus harvest time selection can be crucial for product yield.
Appropriate host cells include yeast, bacteria, archaebacteria, fungi, and insect and animal cells, including mammalian cells. Of particular interest are Saccharomyces cerevisiae and other yeasts, E. coli, Bacillus subtilis, Sf9 cells, C129 cells, 293 cells, Neurospora, BHK, CHO, COS, HeLa cells, HUVEC (human umbilical vein endothelial cells), THP1 cells (a macrophage cell line) and various other human cells and cell lines.
In a preferred embodiment, the metastatic breast cancer or metastatic lung cancer proteins are expressed in mammalian cells. Mammalian expression systems are also known in the art, and include retroviral and adenoviral systems. Of particular use as mammalian promoters are the promoters from mammalian viral genes, since the viral genes are often highly expressed and have a broad host range. Examples include the SV40 early promoter, mouse mammary tumor virus LTR promoter, adenovirus major late promoter, herpes simplex virus promoter, and the CMV promoter (see, e.g., Fernandez & Hoeffler, supra). Typically, transcription termination and polyadenylation sequences recognized by mammalian cells are regulatory regions located 3' to the translation stop codon and thus, together with the promoter elements, flank the coding sequence. Examples of transcription terminator and polyadenylation signals include those derived form SV40.
The methods of introducing exogenous nucleic acid into mammalian hosts, as well as other hosts, is well known in the art, and will vary with the host cell used. Techniques include dextran-mediated transfection, calcium phosphate precipitation, polybrene mediated transfection, protoplast fusion, electroporation, viral infection, encapsulation of the polynucleotide(s) in liposomes, and direct microinjection of the DNA into nuclei.
In a preferred embodiment, metastatic breast cancer or metastatic lung cancer proteins are expressed in bacterial systems. Promoters from bacteriophage may also be used and are known in the art. In addition, synthetic promoters and hybrid promoters are also useful; e.g., the tac promoter is a hybrid of the tip and lac promoter sequences. Furthermore, a bacterial promoter can include naturally occurring promoters of non-bacterial origin that have the ability to bind bacterial RNA polymerase and initiate transcription. In addition to a functioning promoter sequence, an efficient ribosome binding site is desirable. The expression vector may also include a signal peptide sequence that provides for secretion of the metastatic breast cancer or metastatic lung cancer protein in bacteria. The protein is either secreted into the growth media (gram-positive bacteria) or into the periplasmic space, located between the inner and outer membrane of the cell (gram-negative bacteria). The bacterial expression vector may also include a selectable marker gene to allow for the selection of bacterial strains that have been transformed. Suitable selection genes include genes which render the bacteria resistant to drugs such as ampicillin, chloramphenicol, erythromycin, kanamycin, neomycin and tetracycline. Selectable markers also include biosynthetic genes, such as those in the histidine, tryptophan and leucine biosynthetic pathways. These components are assembled into expression vectors. Expression vectors for bacteria are well known in the art, and include vectors for Bacillus subtilis, E. coli, Streptococcus cremoris, and Streptococcus lividans, among others (e.g., Fernandez & Hoeffler, supra). The bacterial expression vectors are transformed into bacterial host cells using techniques well known in the art, such as calcium chloride treatment, electroporation, and others.
In one embodiment, metastatic breast cancer or metastatic lung cancer proteins are produced in insect cells. Expression vectors for the transformation of insect cells, and in particular, baculovirus-based expression vectors, are well known in the art. In a preferred embodiment, metastatic breast cancer or metastatic lung cancer protein is produced in yeast cells. Yeast expression systems are well known in the art, and include expression vectors for Saccharomyces cerevisiae, Candida albicans and C. maltosa, Hansenula polymorpha, Kluyveromyces fragilis sn.dK. lactis, Pichia guillerimondii and P. pastoris, Schizosaccharomyces pombe, and Yarrowia lipolytica. The metastatic breast cancer or metastatic lung cancer protein may also be made as a fusion protein, using techniques well known in the art. Thus, e.g., for the creation of monoclonal antibodies, if the desired epitope is small, the metastatic breast cancer or metastatic lung cancer protein may be fused to a carrier protein to form an immunogen. Alternatively, the metastatic breast cancer or metastatic lung cancer protein may be made as a fusion protein to increase expression for affinity purification purposes, or for other reasons. For example, when the metastatic breast cancer or metastatic lung cancer protein is a metastatic breast cancer or metastatic lung cancer peptide, the nucleic acid encoding the peptide may be linked to other nucleic acid for expression purposes.
In a preferred embodiment, the metastatic breast cancer or metastatic lung cancer protein is purified or isolated after expression. Metastatic breast cancer or metastatic lung cancer proteins may be isolated or purified in a variety of appropriate ways. Standard purification methods include electrophoretic, molecular, immunological and chromatographic techniques, including ion exchange, hydrophobic, affinity, and reverse-phase HPLC chromatography, and chromatofocusing. For example, the metastatic breast cancer or metastatic lung cancer protein may be purified using a standard anti-metastatic breast cancer or metastatic lung cancer protein antibody column. Ultrafiltration and diafiltration techniques, in conjunction with protein concentration, are also useful. For general guidance in suitable purification techniques, see Scopes, Protein Purification (1982). The degree of purification necessary will vary depending on the use of the metastatic breast cancer or metastatic lung cancer protein. In some instances no purification will be necessary.
Once expressed and purified if necessary, the metastatic breast cancer or metastatic lung cancer proteins and nucleic acids are useful in a number of applications. They may be used as immunoselection reagents, as vaccine reagents, as screening agents, etc.
Variants of metastatic breast cancer or metastatic lung cancer proteins
In one embodiment, the metastatic breast cancer or metastatic lung cancer proteins are derivative or variant metastatic breast cancer or metastatic lung cancer proteins as compared to the wild-type sequence. That is, as outlined more fully below, the derivative metastatic breast cancer or metastatic lung cancer peptide will often contain at least one amino acid substitution, deletion or insertion, with amino acid substitutions being particularly preferred. The amino acid substitution, insertion or deletion may occur at a particular residue within the metastatic breast cancer or metastatic lung cancer peptide. Also included within one embodiment of metastatic breast cancer or metastatic lung cancer proteins of the present invention are amino acid sequence variants. These variants typically fall into one or more of three classes: substitutional, insertional or deletional variants. These variants ordinarily are prepared by site specific mutagenesis of nucleotides in the DNA encoding the metastatic breast cancer or metastatic lung cancer protein, using cassette or PCR mutagenesis or other techniques, to produce DNA encoding the variant, and thereafter expressing the DNA in recombinant cell culture as outlined above. However, variant metastatic breast cancer or metastatic lung cancer protein fragments having up to about 100-150 residues may be prepared by in vitro synthesis. Amino acid sequence variants are characterized by the predetermined nature of the variation, a feature that sets them apart from naturally occurring allelic or interspecies variation of the metastatic breast cancer or metastatic lung cancer protein amino acid sequence. The variants typically exhibit the same qualitative biological activity as the naturally occurring analogue, although variants can also be selected which have modified characteristics as will be more fully outlined below.
While the site or region for introducing an amino acid sequence variation is often predetermined, the mutation per se need not be predetermined. For example, in order to optimize the performance of a mutation at a given site, random mutagenesis may be conducted at the target codon or region and the expressed metastatic breast cancer or metastatic lung cancer variants screened for the optimal combination of desired activity. Techniques exist for making substitution mutations at predetermined sites in DNA having a known sequence, e.g., M13 primer mutagenesis and PCR mutagenesis. Screening of the mutants is done using assays of metastatic breast cancer or metastatic lung cancer protein activities.
Amino acid substitutions are typically of single residues; insertions usually will be on the order of from about 1 to 20 amino acids, although considerably larger insertions may be occasionally tolerated. Deletions range from about 1 to about 20 residues, although in some cases deletions may be much larger.
Substitutions, deletions, insertions or any combination thereof may be used to arrive at a final derivative. Generally these changes are done on a few amino acids to minimize the alteration of the molecule. Larger changes may be tolerated in certain circumstances. When small alterations in the characteristics of a metastatic breast cancer or metastatic lung cancer protein are desired, substitutions are generally made in accordance with the amino acid substitution chart provided in the definition section.
Variants typically exhibit the same qualitative biological activity and will elicit the same immune response as the naturally-occurring analog, although variants also are selected to modify the characteristics of the metastatic breast cancer or metastatic lung cancer proteins as needed. Alternatively, the variant may be designed or reorganized such that the biological activity of the metastatic breast cancer or metastatic lung cancer protein is altered. For example, glycosylation sites may be altered or removed. Covalent modifications of metastatic breast cancer or metastatic lung cancer polypeptides are included within the scope of this invention. One type of covalent modification includes reacting targeted amino acid residues of a metastatic breast cancer or metastatic lung cancer polypeptide with an organic derivatizing agent that is capable of reacting with selected side chains or the N-or C-terminal residues of a metastatic breast cancer or metastatic lung cancer polypeptide. Derivatization with bifunctional agents is useful, for instance, for crosslinking metastatic breast cancer or metastatic lung cancer polypeptides to a water-insoluble support matrix or surface for use in the method for purifying anti-metastatic breast cancer or metastatic lung cancer polypeptide antibodies or screening assays, as is more fully described below. Commonly used crosslinking agents include, e.g., l,l-bis(diazoacetyl)-2-phenylethane, glutaraldehyde, N-hydroxysuccinimide esters, e.g., esters with 4-azidosalicylic acid, homobifunctional imidoesters, including disuccinimidyl esters such as 3,3'-dithiobis(succinimidylpropionate), bifunctional maleimides such as bis-N-maleimido-l,8-octane and agents such as methyl-3-((p- azidophenyl)dithio)propioimidate. Other modifications include deamidation of glutaminyl and asparaginyl residues to the corresponding glutamyl and aspartyl residues, respectively, hydroxylation of proline and lysine, phosphorylation of hydroxyl groups of seryl, threonyl or tyrosyl residues, methylation of the γ-amino groups of lysine, arginine, and histidine side chains (Creighton, Proteins: Structure and Molecular Properties, pp. 79-86 (1983)), acetylation of the N-terminal amine, and amidation of any C-terminal carboxyl group.
Another type of covalent modification of the metastatic breast cancer or metastatic lung cancer polypeptide encompassed by this invention is an altered native glycosylation pattern of the polypeptide. "Altering the native glycosylation pattern" is intended herein to mean adding to or deleting one or more carbohydrate moieties of a native sequence metastatic breast cancer or metastatic lung cancer polypeptide. Glycosylation patterns can be altered in many ways. For example the use of different cell types to express metastatic breast cancer or metastatic lung cancer-associated sequences can result in different glycosylation patterns.
Addition of glycosylation sites to metastatic breast cancer or metastatic lung cancer polypeptides may also be accomplished by altering the amino acid sequence thereof. The alteration may be made, e.g., by the addition of, or substitution by, one or more serine or threonine residues to the native sequence metastatic breast cancer or metastatic lung cancer polypeptide (for 0-linked glycosylation sites). The metastatic breast cancer or metastatic lung cancer amino acid sequence may optionally be altered through changes at the DNA level, particularly by mutating the DNA encoding the metastatic breast cancer or metastatic lung cancer polypeptide at preselected bases such that codons are generated that will translate into the desired amino acids.
Another means of increasing the number of carbohydrate moieties on the metastatic breast cancer or metastatic lung cancer polypeptide is by chemical or enzymatic coupling of glycosides to the polypeptide. Such methods are described in the art, e.g., in WO 87/05330, and in Aplin & Wriston, CRC Crit. Rev. Biochem., pp. 259-306 (1981).
Removal of carbohydrate moieties present on the metastatic breast cancer or metastatic lung cancer polypeptide may be accomplished chemically or enzymatically or by mutational substitution of codons encoding for amino acid residues that serve as targets for glycosylation. Chemical deglycosylation techniques are known in the art and described, for instance, by Hakimuddin, et al, Arch. Biochem. Biophys., 259:52 (1987) and by Edge et al, Anal. Biochem., 118:131 (1981). Enzymatic cleavage of carbohydrate moieties on polypeptides can be achieved by the use of a variety of endo-and exo-glycosidases as described by Thotakura et al, Meth. Enzymol., 138:350 (1987).
Another type of covalent modification of metastatic breast cancer or metastatic lung cancer comprises linking the metastatic breast cancer or metastatic lung cancer polypeptide to one of a variety of nonproteinaceous polymers, e.g., polyethylene glycol, polypropylene glycol, or polyoxyalkylenes, in the manner set forth in U.S. Patent Nos. 4,640,835; 4,496,689; 4,301,144; 4,670,417; 4,791,192 or 4,179,337, each of which is hereby incorporated by reference herein.
Metastatic breast cancer or metastatic lung cancer polypeptides of the present invention may also be modified in a way to form chimeric molecules comprising a metastatic breast cancer or metastatic lung cancer polypeptide fused to another, heterologous polypeptide or amino acid sequence. In one embodiment, such a chimeric molecule comprises a fusion of a metastatic breast cancer or metastatic lung cancer polypeptide with a tag polypeptide which provides an epitope to which an anti-tag antibody can selectively bind. The epitope tag is generally placed at the amino-or carboxyl-terminus of the metastatic breast cancer or metastatic lung cancer polypeptide. The presence of such epitope-tagged forms of a metastatic breast cancer or metastatic lung cancer polypeptide can be detected using an antibody against the tag polypeptide. Also, provision of the epitope tag enables the metastatic breast cancer or metastatic lung cancer polypeptide to be readily purified by affinity purification using an anti-tag antibody or another type of affinity matrix that binds to the epitope tag. In an alternative embodiment, the chimeric molecule may comprise a fusion of a metastatic breast cancer or metastatic lung cancer polypeptide with an immunoglobulin or a particular region of an immunoglobulin. For a bivalent form of the chimeric molecule, such a fusion could be to the Fc region of an IgG molecule. Various tag polypeptides and their respective antibodies are well known and examples include poly-histidine (poly-his) or poly-histidine-glycine (poly-his-gly) tags; HIS6 and metal chelation tags, the flu HA tag polypeptide and its antibody 12CA5 (Field et al, Mol. Cell. Biol. 8:2159-2165 (1988)); the c-myc tag and the 8F9, 3C7, 6E10, G4, B7 and 9E10 antibodies thereto (Evan et al, Molecular and Cellular Biology 5:3610-3616 (1985)); and the Herpes Simplex virus glycoprotein D (gD) tag and its antibody (Paborsky et al,
Protein Engineering 3(6):547-553 (1990)). Other tag polypeptides include the Flag-peptide (Hopp et al, BioTechnology 6: 1204-1210 (1988)); the KT3 epitope peptide (Martin et al, Science 255:192-194 (1992)); rubulin epitope peptide (Skinner et al, J. Biol. Chem. 266:15163-15166 (1991)); and the T7 gene 10 protein peptide tag (Lutz-Freyermuth et al, Proc. Natl Acad. Sci. USA 87:6393-6397 (1990)).
Also included are other metastatic breast cancer or metastatic lung cancer proteins of the metastatic breast cancer or metastatic lung cancer family, and metastatic breast cancer or metastatic lung cancer proteins from other organisms, which are cloned and expressed as outlined below. Thus, probe or degenerate polymerase chain reaction (PCR) primer sequences may be used to find other related metastatic breast cancer or metastatic lung cancer proteins from primates or other organisms. As will be appreciated by those in the art, particularly useful probe and/or PCR primer sequences include unique areas of the metastatic breast cancer or metastatic lung cancer nucleic acid sequence. As is generally known in the art, preferred PCR primers are from about 15 to about 35 nucleotides in length, with from about 20 to about 30 being preferred, and may contain inosine as needed. PCR reaction conditions are well known in the art (e.g., Innis, PCR Protocols, supra).
Antibodies to metastatic breast cancer or metastatic lung cancer proteins
In a preferred embodiment, when a metastatic breast cancer or metastatic lung cancer protein is to be used to generate antibodies, e.g., for immunotherapy or immunodiagnosis, the metastatic breast cancer or metastatic lung cancer protein should share at least one epitope or determinant with the full length protein. By "epitope" or "determinant" herein is typically meant a portion of a protein which will generate and/or bind an antibody or T-cell receptor in the context of MHC. Thus, in most instances, antibodies made to a smaller metastatic breast cancer or metastatic lung cancer protein will be able to bind to the full-length protein, particularly linear epitopes. In a preferred embodiment, the epitope is unique; that is, antibodies generated to a unique epitope show little or no cross- reactivity.
Methods of preparing polyclonal antibodies are well known (e.g., Coligan, supra; and Harlow & Lane, supra). Polyclonal antibodies can be raised in a mammal, e.g., by one or more injections of an immunizing agent and, if desired, an adjuvant. Typically, the immunizing agent and/or adjuvant will be injected in the mammal by multiple subcutaneous or intraperitoneal injections. The immunizing agent may include a protem encoded by a nucleic acid of Tables 1-12 or fragment thereof or a fusion protein thereof. It may be useful to conjugate the immunizing agent to a protein known to be immunogenic in the mammal being immunized. Immunogenic proteins include, e.g., keyhole limpet hemocyanin, serum albumin, bovine thyroglobulin, and soybean trypsin inhibitor. Adjuvants include, e.g., Freund's complete adjuvant and MPL-TDM adjuvant (monophosphoryl Lipid A, synthetic trehalose dicorynomycolate). The immunization protocol may be selected by one skilled in the art.
The antibodies may, alternatively, be monoclonal antibodies. Monoclonal antibodies may be prepared using hybridoma methods, such as those described by Kohler & Milstein, Nature 256:495 (1975). In a hybridoma method, a mouse, hamster, or other appropriate host animal, is typically immunized with an immunizing agent to elicit lymphocytes that produce or are capable of producing antibodies that will specifically bind to the immunizing agent. Alternatively, the lymphocytes may be immunized in vitro. The immunizing agent will typically include a polypeptide encoded by a nucleic acid of Tables 1- 12, or fragment thereof, or a fusion protein thereof. Generally, either peripheral blood lymphocytes ("PBLs") are used if cells of human origin are desired, or spleen cells or lymph node cells are used if non-human mammalian sources are desired. The lymphocytes are then fused with an immortalized cell line using a suitable fusing agent, such as polyethylene glycol, to form a hybridoma cell (Goding, Monoclonal Antibodies: Principles and Practice, pp. 59-103 (1986)). Immortalized cell lines are usually transformed mammalian cells, particularly myeloma cells of rodent, bovine and primate origin. Usually, rat or mouse myeloma cell lines are employed. The hybridoma cells may be cultured in a suitable culture medium that preferably contains one or more substances that inhibit the growth or survival of the unfused, immortalized cells. For example, if the parental cells lack the enzyme hypoxanthine guanine phosphoribosyl transferase (HGPRT or HPRT), the culture medium for the hybridomas typically will include hypoxanthine, aminopterin, and thymidine ("HAT medium"), which substances prevent the growth of HGPRT-deficient cells.
In one embodiment, the antibodies are bispecific antibodies. Bispecific antibodies are typically monoclonal, preferably human or humanized, antibodies that have binding specificities for at least two different antigens or that have binding specificities for two epitopes on the same antigen. In one embodiment, one of the binding specificities is for a protein encoded by a nucleic acid of Tables 1-12 or a fragment thereof, the other one is for any other antigen, and preferably for a cell-surface protem or receptor or receptor subunit, preferably one that is tumor specific. Alternatively, tetramer-type technology may create multivalent reagents.
In a preferred embodiment, the antibodies to metastatic breast cancer or metastatic lung cancer protein are capable of reducing or eliminating a biological function of a metastatic breast cancer or metastatic lung cancer protein, as is described below. That is, the addition of anti-metastatic breast cancer or metastatic lung cancer protein antibodies (either polyclonal or preferably monoclonal) to metastatic breast cancer or metastatic lung cancer tissue (or cells containing metastatic breast cancer or metastatic lung cancer) may reduce or eliminate the metastatic breast cancer or metastatic lung cancer. Generally, at least a 25% decrease in activity, growth, size or the like is preferred, with at least about 50% being particularly preferred and about a 95-100%) decrease being especially preferred.
In a preferred embodiment the antibodies to the metastatic breast cancer or metastatic lung cancer proteins are humanized antibodies (e.g., Xenerex Biosciences, Mederex, Inc., Abgenix, Inc., Protein Design Labs, Inc.) Humanized forms of non-human (e.g., murine) antibodies are chimeric molecules of immunoglobulins, immunoglobulin chains or fragments thereof (such as Fv, Fab, Fab', F(ab')2 or other antigen-binding subsequences of antibodies) which contain minimal sequence derived from non-human immunoglobulin. Humanized antibodies include human immunoglobulins (recipient antibody) in which residues from a complementary determining region (CDR) of the recipient are replaced by residues from a CDR of a non-human species (donor antibody) such as mouse, rat or rabbit having the desired specificity, affinity and capacity. In some instances, Fv framework residues of the human immunoglobulin are replaced by corresponding non- human residues. Humanized antibodies may also comprise residues which are found neither in the recipient antibody nor in the imported CDR or framework sequences. In general, a humanized antibody will comprise substantially all of at least one, and typically two, variable domains, in which all or substantially all of the CDR regions correspond to those of a non- human immunoglobulin and all or substantially all of the framework (FR) regions are those of a human immunoglobulin consensus sequence. The humanized antibody optimally also will comprise at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin (Jones et al, Nature 321 :522-525 (1986); Riechmann et al, Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992)). Humanization can be essentially performed following the method of Winter and co-workers (Jones et al, Nature 321:522-525 (1986); Riechmann et al, Nature 332:323-327 (1988); Verhoeyen et al, Science 239:1534-1536 (1988)), by substituting rodent CDRs or CDR sequences for the corresponding sequences of a human antibody. Accordingly, such humanized antibodies are chimeric antibodies (U.S. Patent No. 4,816,567, which is hereby incorporated by reference herein.), wherein substantially less than an intact human variable domain has been substituted by the corresponding sequence from a non-human species. Human-like antibodies can also be produced using various techniques known in the art, including phage display libraries (Hoogenboom & Winter, J. Mol. Biol. 227:381 (1991); Marks et al, J. Mol. Biol. 222:581 (1991)). The techniques of Cole et al. and Boerner et al. are also available for the preparation of human monoclonal antibodies (Cole et al, Monoclonal Antibodies and Cancer Therapy, p. 77 (1985) and Boerner et al, J. Immunol. 147(l):86-95 (1991)). Similarly, human antibodies can be made by introducing of human immunoglobulin loci into transgenic animals, e.g., mice in which the endogenous immunoglobulin genes have been partially or completely inactivated. Upon challenge, human antibody production is observed, which closely resembles that seen in humans in virtually all respects, including gene rearrangement, assembly, and antibody repertoire. This approach is described, e.g., in U.S. Patent Nos. 5,545,807; 5,545,806; 5,569,825; 5,625,126; 5,633,425; 5,661,016, each of which is hereby incorporated by reference herein, and in the following scientific publications: Marks et al, Bio/Technology 10:779-783 (1992); Lonberg et al, Nature 368:856-859 (1994); Morrison, Nature 368:812-13 (1994); Fishwild et al, Nature Biotechnology 14:845-51 (1996); Neuberger, Nature Biotechnology 14:826 (1996); Lonberg & Huszar, Intern. Rev. Immunol. 13:65-93 (1995).
By immunotherapy is meant treatment of metastatic breast cancer or metastatic lung cancer with an antibody raised against a metastatic breast cancer or metastatic lung cancer proteins. As used herein, immunotherapy can be passive or active. Passive immunotherapy as defined herein is the passive transfer of antibody to a recipient (patient). Active immunization is the induction of antibody and/or T-cell responses in a recipient (patient). Induction of an immune response is the result of providing the recipient with an antigen to which antibodies are raised. The antigen may be provided by injecting a polypeptide against which antibodies are desired to be raised into a recipient, or contacting the recipient with a nucleic acid capable of expressing the antigen and under conditions for expression of the antigen, leading to an immune response.
In a preferred embodiment the metastatic breast cancer or metastatic lung cancer proteins against which antibodies are raised are secreted proteins as described above. Without being bound by theory, antibodies used for treatment, bind and prevent the secreted protein from binding to its receptor, thereby inactivating the secreted metastatic breast cancer or metastatic lung cancer protein.
In another preferred embodiment, the metastatic breast cancer or metastatic lung cancer protein to which antibodies are raised is a transmembrane protein. Without being bound by theory, antibodies used for this treatment typically bind the extracellular domain of the metastatic breast cancer or metastatic lung cancer protein and prevent it from binding to other proteins, such as circulating ligands or cell-associated molecules. The antibody may cause down-regulation of the transmembrane metastatic breast cancer or metastatic lung cancer protein. The antibody may be a competitive, non-competitive or uncompetitive inhibitor of protein binding to the extracellular domain of the metastatic breast cancer or metastatic lung cancer protein. The antibody may be an antagonist of the metastatic breast cancer or metastatic lung cancer protem or may prevent activation of the transmembrane metastatic breast cancer or metastatic lung cancer protein. In some embodiments, when the antibody prevents the binding of other molecules to the metastatic breast cancer or metastatic lung cancer protein, the antibody prevents growth of the cell. The antibody may also be used to target or sensitize the cell to cytotoxic agents, including, but not limited to TNF-α, TNF-β, IL-1, INF-γ and IL-2, or chemotherapeutic agents including 5FU, vinblastine, actinomycin D, cisplatin, methotrexate, and the like. In some instances the antibody belongs to a sub-type that activates serum complement when complexed with the transmembrane protein thereby mediating cytotoxicity or antigen-dependent cytotoxicity (ADCC). Thus, metastatic breast cancer or metastatic lung cancer is treated by administering to a patient antibodies directed against the transmembrane metastatic breast cancer or metastatic lung cancer protein. Antibody-labeling may activate a co-toxin, localize a toxin payload, or otherwise provide means to locally ablate cells. In another preferred embodiment, the antibody is conjugated to an effector moiety.
The effector moiety can be any number of molecules, including labeling moieties such as radioactive labels or fluorescent labels, or can be a therapeutic moiety. In one aspect the therapeutic moiety is a small molecule that modulates the activity of the metastatic breast cancer or metastatic lung cancer protein. In another aspect the therapeutic moiety modulates the activity of molecules associated with or in close proximity to the metastatic breast cancer or metastatic lung cancer protein. The therapeutic moiety may inhibit enzymatic activity such as protease or collagenase activity associated with metastatic breast cancer or metastatic lung cancer.
In a preferred embodiment, the therapeutic moiety can also be a cytotoxic agent. In this method, targeting the cytotoxic agent to metastatic breast cancer or metastatic lung cancer tissue or cells results in a reduction in the number of afflicted cells, thereby reducing symptoms associated with metastatic breast cancer or metastatic lung cancer. Cytotoxic agents are numerous and varied and include, but are not limited to, cytotoxic drags or toxins or active fragments of such toxins. Suitable toxins and their corresponding fragments include diphtheria A chain, exotoxin A chain, ricin A chain, abrin A chain, curcin, crotin, phenomycin, enomycin and the like. Cytotoxic agents also include radiochemicals made by conjugating radioisotopes to antibodies raised against metastatic breast cancer or metastatic lung cancer proteins, or binding of a radionuclide to a chelating agent that has been covalently attached to the antibody. Targeting the therapeutic moiety to transmembrane metastatic breast cancer or metastatic lung cancer proteins not only serves to increase the local concentration of therapeutic moiety in the metastatic breast cancer or metastatic lung cancer afflicted area, but also serves to reduce deleterious side effects that may be associated with the therapeutic moiety.
In another preferred embodiment, the metastatic breast cancer or metastatic lung cancer protein against which the antibodies are raised is an intracellular protein. In this case, the antibody may be conjugated to a protein or other entity which facilitates entry into the cell. In one case, the antibody enters the cell by endocytosis. In another embodiment, a nucleic acid encoding the antibody is administered to the individual or cell. Moreover, wherein the metastatic breast cancer or metastatic lung cancer protein can be targeted within a cell, i.e., the nucleus, an antibody thereto contains a signal for that target localization, i.e., a nuclear localization signal.
The metastatic breast cancer or metastatic lung cancer antibodies of the invention specifically bind to metastatic breast cancer or metastatic lung cancer proteins. By
"specifically bind" herein is meant that the antibodies bind to the protein with a Kd of at least about 0.1 mM, more usually at least about 1 μM, preferably at least about 0.1 μM or better, and most preferably, 0.01 μM or better. Selectivity of binding is also important.
Detection of metastatic breast cancer or metastatic lung cancer sequence for diagnostic and therapeutic applications
In one aspect, the RNA expression levels of genes are determined for different cellular states in the metastatic breast cancer or metastatic lung cancer phenotype. Expression levels of genes in normal tissue (i.e., not undergoing metastatic breast cancer or metastatic lung cancer) and in metastatic breast cancer or metastatic lung cancer tissue (and in some cases, for varying severities of metastatic breast cancer or metastatic lung cancer that relate to prognosis, as outlined below) are evaluated to provide expression profiles. An expression profile of a particular cell state or point of development is essentially a "fingerprint" of the state. While two states may have any particular gene similarly expressed, the evaluation of a number of genes simultaneously allows the generation of a gene expression profile that is reflective of the state of the cell. By comparing expression profiles of cells in different states, information regarding which genes are important (including both up- and down-regulation of genes) in each of these states is obtained. Then, diagnosis may be performed or confirmed to determine whether a tissue sample has the gene expression profile of normal or cancerous tissue. This will provide for molecular diagnosis of related conditions.
"Differential expression," or grammatical equivalents as used herein, refers to qualitative or quantitative differences in the temporal and/or cellular gene expression patterns within and among cells and tissue. Thus, a differentially expressed gene can qualitatively have its expression altered, including an activation or inactivation, in, e.g., normal versus metastatic breast cancer or metastatic lung cancer tissue. Genes may be turned on or turned off in a particular state, relative to another state thus permitting comparison of two or more states. A qualitatively regulated gene will exhibit an expression pattern within a state or cell type which is detectable by standard techniques. Some genes will be expressed in one state or cell type, but not in both. Alternatively, the difference in expression may be quantitative, e.g., in that expression is increased or decreased; i.e., gene expression is either upregulated, resulting in an increased amount of transcript, or downregulated, resulting in a decreased amount of transcript. The degree to which expression differs need only be large enough to quantify via standard characterization techniques as outlined below, such as by use of GENECHIP® (DNA microarray) expression arrays from Affymetrix, Inc. (Santa Clara, CA), as described in Lockhart et al, Nature Biotechnology 14:1675-1680 (1996), hereby expressly incorporated by reference. Other techniques include, but are not limited to, quantitative reverse transcriptase PCR, northern analysis and RNase protection. As outlined above, preferably the change in expression (i.e., upregulation or dowmegulation) is typically at least about 50%, more preferably at least about 100%), more preferably at least about 150%), more preferably at least about 200%, with from 300 to at least 1000%) being especially preferred.
Evaluation may be at the gene transcript, or the protein level. The amount of gene expression may be monitored using nucleic acid probes to the DNA or RNA equivalent of the gene transcript, and the quantification of gene expression levels, or, alternatively, the final gene product itself (protein) can be monitored, e.g., with antibodies to the metastatic breast cancer or metastatic lung cancer protein and standard immunoassays (ELISAs, etc.) or other techniques, including mass spectroscopy assays, 2D gel electrophoresis assays, etc. Proteins corresponding to metastatic breast cancer or metastatic lung cancer genes, i.e., those identified as being important in a metastatic breast cancer or metastatic lung cancer phenotype, can be evaluated in a metastatic breast cancer or metastatic lung cancer diagnostic test. In a preferred embodiment, gene expression monitoring is performed simultaneously on a number of genes.
The metastatic breast cancer or metastatic lung cancer nucleic acid probes may be attached to biochips as outlined herein for the detection and quantification of metastatic breast cancer or metastatic lung cancer sequences in a particular cell. The assays are further described below in the example. PCR techniques can be used to provide greater sensitivity. Multiple protein expression monitoring can be performed as well. Similarly, these assays may be performed on an individual basis as well.
In a preferred embodiment nucleic acids encoding the metastatic breast cancer or metastatic lung cancer protein are detected. Although DNA or RNA encoding the metastatic breast cancer or metastatic lung cancer protein may be detected, of particular interest are methods wherein an mRNA encoding a metastatic breast cancer or metastatic lung cancer protein is detected. Probes to detect mRNA can be a nucleotide/deoxynucleotide probe that is complementary to and hybridizes with the mRNA and includes, but is not limited to, oligonucleotides, cDNA or RNA. Probes also should contain a detectable label, as defined herein. In one method the mRNA is detected after immobilizing the nucleic acid to be examined on a solid support such as nylon membranes and hybridizing the probe with the sample. Following washing to remove the non-specifically bound probe, the label is detected. In another method detection of the mRNA is performed in situ. In this method permeabilized cells or tissue samples are contacted with a detectably labeled nucleic acid probe for sufficient time to allow the probe to hybridize with the target mRNA. Following washing to remove the non-specifically bound probe, the label is detected. For example a digoxygenin labeled riboprobe (RNA probe) that is complementary to the mRNA encoding a metastatic breast cancer or metastatic lung cancer protein is detected by binding the digoxygenin with an anti-digoxygenin secondary antibody and developed with nitro blue tetrazolium and 5-bromo-4-chloro-3-indoyl phosphate.
In a preferred embodiment, various proteins from the three classes of proteins as described herein (secreted, transmembrane or intracellular proteins) are used in diagnostic assays. The metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing metastatic breast cancer or metastatic lung cancer sequences are used in diagnostic assays. This can be performed on an individual gene or corresponding polypeptide level. In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes and/or corresponding polypeptides. As described and defined herein, metastatic breast cancer or metastatic lung cancer proteins, including intracellular, transmembrane or secreted proteins, find use as markers of metastatic breast cancer or metastatic lung cancer. Detection of these proteins in putative metastatic breast cancer or metastatic lung cancer tissue allows for detection or diagnosis of metastatic breast cancer or metastatic lung cancer. In one embodiment, antibodies are used to detect metastatic breast cancer or metastatic lung cancer proteins. A preferred method separates proteins from a sample by electrophoresis on a gel (typically a denaturing and reducing protein gel, but may be another type of gel, including isoelectric focusing gels and the like). Following separation of proteins, the metastatic breast cancer or metastatic lung cancer protein is detected, e.g., by immunoblotting with antibodies raised against the metastatic breast cancer or metastatic lung cancer protein. Methods of immunoblotting are well known to those of ordinary skill in the art.
In another preferred method, antibodies to the metastatic breast cancer or metastatic lung cancer protein find use in in situ imaging techniques, e.g., in histology (e.g., Methods in Cell Biology: Antibodies in Cell Biology, volume 37 (Asai, ed. 1993)). In this method cells are contacted with from one to many antibodies to the metastatic breast cancer or metastatic lung cancer protein(s). Following washing to remove non-specific antibody binding, the presence of the antibody or antibodies is detected. In one embodiment the antibody is detected by incubating with a secondary antibody that contains a detectable label, e.g., multicolor fluorescence or confocal imaging. In another method the primary antibody to the metastatic breast cancer or metastatic lung cancer protein(s) contains a detectable label, e.g., an enzyme marker that can act on a substrate. In another preferred embodiment each one of multiple primary antibodies contains a distinct and detectable label. This method finds particular use in simultaneous screening for a plurality of metastatic breast cancer or metastatic lung cancer proteins. Many other histological imaging techniques are also provided by the invention.
In a preferred embodiment the label is detected in a fluorometer which has the ability to detect and distinguish emissions of different wavelengths. In addition, a fluorescence activated cell sorter (FACS) can be used in the method. In another preferred embodiment, antibodies find use in diagnosing metastatic breast cancer or metastatic lung cancer from blood, serum, plasma, stool, and other samples. Such samples, therefore, are useful as samples to be probed or tested for the presence of metastatic breast cancer or metastatic lung cancer proteins. Antibodies can be used to detect a metastatic breast cancer or metastatic lung cancer protein by previously described immunoassay techniques including ELISA, immunoblotting (western blotting), immunoprecipitation, BIACORE technology and the like. Conversely, the presence of antibodies may indicate an immune response against an endogenous metastatic breast cancer or metastatic lung cancer protein or vaccine. In a preferred embodiment, in situ hybridization of labeled metastatic breast cancer or metastatic lung cancer nucleic acid probes to tissue arrays is done. For example, arrays of tissue samples, including metastatic breast cancer or metastatic lung cancer tissue and/or normal tissue, are made, ht situ hybridization (see, e.g., Ausubel, supra) is then performed. When comparing the fingerprints between an individual and a standard, the skilled artisan can make a diagnosis, a prognosis, or a prediction based on the findings. It is further understood that the genes which indicate the diagnosis may differ from those which indicate the prognosis and molecular profiling of the condition of the cells may lead to distinctions between responsive or refractory conditions or may be predictive of outcomes.
In a preferred embodiment, the metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing metastatic breast cancer or metastatic lung cancer sequences are used in prognosis assays. As above, gene expression profiles can be generated that correlate to metastatic breast cancer or metastatic lung cancer, in terms of long term prognosis. Again, this may be done on either a protein or gene level, with the use of genes being preferred. As above, metastatic breast cancer or metastatic lung cancer probes may be attached to biochips for the detection and quantification of metastatic breast cancer or metastatic lung cancer sequences in a tissue or patient. The assays proceed as outlined above for diagnosis. PCR method may provide more sensitive and accurate quantification.
Assays for therapeutic compounds
In a preferred embodiment members of the three classes of proteins as described herein are used in drug screening assays. The metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing metastatic breast cancer or metastatic lung cancer sequences are used in drug screening assays or by evaluating the effect of drag candidates on a "gene expression profile" or expression profile of polypeptides. In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent (e.g., Zlokarnik, et al, Science 279:84-8 (1998); Heid, Genome Res 6:986-94, 1996).
In a preferred embodiment, the metastatic breast cancer or metastatic lung cancer proteins, antibodies, nucleic acids, modified proteins and cells containing the native or modified metastatic breast cancer or metastatic lung cancer proteins are used in screening assays. That is, the present invention provides novel methods for screening for compositions which modulate the metastatic breast cancer or metastatic lung cancer phenotype or an identified physiological function of a metastatic breast cancer or metastatic lung cancer protein. As above, this can be done on an individual gene level or by evaluating the effect of drag candidates on a "gene expression profile". In a preferred embodiment, the expression profiles are used, preferably in conjunction with high throughput screening techniques to allow monitoring for expression profile genes after treatment with a candidate agent, see Zlokamik, supra.
Having identified the differentially expressed genes herein, a variety of assays may be applied. In a preferred embodiment, assays may be ran on an individual gene or protein level. That is, having identified a particular gene with altered regulation in metastatic breast cancer or metastatic lung cancer, test compounds can be screened for the ability to modulate gene expression or for binding to the metastatic breast cancer or metastatic lung cancer protein. "Modulation" thus includes an increase or a decrease in gene expression. The preferred amount of modulation will depend on the original change of the gene expression in normal versus tissue undergoing metastatic breast cancer or metastatic lung cancer, with changes of at least 10%>, preferably 50%, more preferably 100-300%), and in some embodiments 300-1000% or greater. Thus, if a gene exhibits a 4-fold increase in metastatic breast cancer or metastatic lung cancer tissue compared to normal tissue, a decrease of about four-fold is often desired; similarly, a 10-fold decrease in metastatic breast cancer or metastatic lung cancer tissue compared to normal tissue often provides a target value of a 10- fold increase in expression to be induced by the test compound.
The amount of gene expression may be monitored using nucleic acid probes and the quantification of gene expression levels, or, alternatively, the gene product itself can be monitored, e.g., through the use of antibodies to the metastatic breast cancer or metastatic lung cancer protein and standard immunoassays. Proteomics and separation techniques may also allow quantification of expression.
In a preferred embodiment, gene or protein expression monitoring of a number of entities, i.e., an expression profile, is monitored simultaneously. Such profiles will typically involve a plurality of those entities described herein.
In this embodiment, the metastatic breast cancer or metastatic lung cancer nucleic acid probes are attached to biochips as outlined herein for the detection and quantification of metastatic breast cancer or metastatic lung cancer sequences in a particular cell. Alternatively, PCR may be used. Thus, a series, e.g., of microtiter plate, may be used with dispensed primers in desired wells. A PCR reaction can then be performed and analyzed for each well.
Expression monitoring can be performed to identify compounds that modify the expression of one or more metastatic breast cancer or metastatic lung cancer-associated sequences, e.g., a polynucleotide sequence set out in Tables 1-12. Generally, in a preferred embodiment, a test compound is added to the cells prior to analysis. Moreover, screens are also provided to identify agents that modulate metastatic breast cancer or metastatic lung cancer, modulate metastatic breast cancer or metastatic lung cancer proteins, bind to a metastatic breast cancer or metastatic lung cancer protein, or interfere with the binding of a metastatic breast cancer or metastatic lung cancer protein and an antibody, substrate, or other binding partner.
The term "test compound" or "drug candidate" or "modulator" or grammatical equivalents as used herein describes any molecule, e.g., protein, oligopeptide, small organic molecule, polysaccharide, polynucleotide, etc., to be tested for the capacity to directly or indirectly alter the metastatic breast cancer or metastatic lung cancer phenotype or the expression of a metastatic breast cancer or metastatic lung cancer sequence, e.g., a nucleic acid or protein sequence. In preferred embodiments, modulators alter expression profiles of nucleic acids or proteins provided herein. In one embodiment, the modulator suppresses a metastatic breast cancer or metastatic lung cancer phenotype, e.g., to a normal tissue fingerprint. In another embodiment, a modulator induces a metastatic breast cancer or metastatic lung cancer phenotype. Generally, a plurality of assay mixtures are run in parallel with different agent concentrations to obtain a differential response to the various concentrations. Typically, one of these concentrations serves as a negative control, i.e., at zero concentration or below the level of detection. In one aspect, a modulator will neutralize the effect of a metastatic breast cancer or metastatic lung cancer protein. By "neutralize" is meant that activity of a protein and the consequent effect on the cell is inhibited or blocked.
In certain embodiments, combinatorial libraries of potential modulators will be screened for an ability to bind to a metastatic breast cancer or metastatic lung cancer polypeptide or to modulate activity. Conventionally, new chemical entities with useful properties are generated by identifying a chemical compound (called a "lead compound") with some desirable property or activity, e.g., inhibiting activity, creating variants of the lead compound, and evaluating the property and activity of those variant compounds. Often, high throughput screening (HTS) methods are employed for such an analysis.
In one preferred embodiment, high throughput screening methods involve providing a library containing a large number of potential therapeutic compounds (candidate compounds). Such "combinatorial chemical libraries" are then screened in one or more assays to identify those library members (particular chemical species or subclasses) that display a desired characteristic activity. The compounds thus identified can serve as conventional "lead compounds" or can themselves be used as potential or actual therapeutics.
A combinatorial chemical library is a collection of diverse chemical compounds generated by either chemical synthesis or biological synthesis by combining a number of chemical "building blocks" such as reagents. For example, a linear combinatorial chemical library, such as a polypeptide (e.g., mutein) library, is formed by combining a set of chemical building blocks called amino acids in every possible way for a given compound length (i.e., the number of amino acids in a polypeptide compound). Millions of chemical compounds can be synthesized through such combinatorial mixing of chemical building blocks (Gallop et al, J. Med. Chem. 37(9):1233-1251 (1994)). Preparation and screening of combinatorial chemical libraries is well known to those of skill in the art. Such combinatorial chemical libraries include, but are not limited to, peptide libraries (see, e.g., U.S. Patent No. 5,010,175, Furka, Pept. Prot. Res. 37:487-493 (1991), Houghton et al, Nature, 354:84-88 (1991)), peptoids (PCT Publication No WO 91/19735), encoded peptides (PCT Publication WO 93/20242), random bio-oligomers (PCT Publication WO 92/00091), benzodiazepines (U.S. Pat. No. 5,288,514, which is hereby incorporated by reference herein), diversomers such as hydantoins, benzodiazepines and dipeptides (Hobbs et al, Proc. Nat. Acad. Sci. USA 90:6909-6913 (1993)), vinylogous polypeptides (Hagihara et al, J. Amer. Chem. Soc. 114:6568 (1992)), nonpeptidal peptidomimetics with a Beta-D-Glucose scaffolding (Hirschmann et al, J. Amer. Chem. Soc. 114:9217-9218 (1992)), analogous organic syntheses of small compound libraries (Chen et al, J. Amer. Chem. Soc. 116:2661 (1994)), oligocarbamates (Cho, et al, Science 261:1303 (1993)), and/or peptidyl phosphonates (Campbell et al, J. Org. Chem. 59:658 (1994)). See, generally, Gordon et al, J. Med. Chem. 37:1385 (1994), nucleic acid libraries (see, e.g., Stiategene, Corp.), peptide nucleic acid libraries (see, e.g., U.S. Patent 5,539,083, which is hereby incorporated by reference herein), antibody libraries (see, e.g., Vaughn et al, Nature Biotechnology 14(3):309-314 (1996), and PCT/US96/10287), carbohydrate libraries (see, e.g., Liang et al, Science 274:1520-1522 (1996), and U.S. Patent No. 5,593,853, which is hereby incorporated by reference herein), and small organic molecule libraries (see, e.g., benzodiazepines, Baum, C&EN, Jan 18, page 33 (1993); isoprenoids, U.S. Patent No.
5,569,588; thiazolidinones and metathiazanones, U.S. Patent No. 5,549,974; pyrrolidines, U.S. Patent Nos. 5,525,735 and 5,519,134; morpholino compounds, U.S. Patent No. 5,506,337; benzodiazepines, U.S. Patent No. 5,288,514; and the like, each of which is hereby incorporated by reference herein). Devices for the preparation of combinatorial libraries are commercially available
(see, e.g., 357 MPS, 390 MPS, Advanced Chem Tech, Louisville KY, Symphony, Rainin, Wobum, MA, 433A Applied Biosystems, Foster City, CA, 9050 Plus, Millipore, Bedford, MA).
A number of well known robotic systems have also been developed for solution phase chemistries. These systems include automated workstations like the automated synthesis apparatus developed by Takeda Chemical Industries, LTD. (Osaka, Japan) and many robotic systems utilizing robotic arms (Zymate II, Zymark Corporation, Hopkinton, Mass.; Orca, Hewlett-Packard, Palo Alto, Calif), which mimic the manual synthetic operations performed by a chemist. The above devices, with appropriate modification, are suitable for use with the present invention. In addition, numerous combinatorial libraries are themselves commercially available (see, e.g., ComGenex, Princeton, N.J.; Asinex, Moscow, RU; Tripos, Inc., St. Louis, MO; ChemStar, Ltd, Moscow, RU; 3D Pharmaceuticals, Exton, PA; Martek Biosciences, Columbia, MD, etc.).
The assays to identify modulators are amenable to high throughput screening. Preferred assays thus detect modulation of metastatic breast cancer or metastatic lung cancer gene transcription, polypeptide expression, and polypeptide activity.
High throughput assays for evaluating the presence, absence, quantification, or other properties of particular nucleic acids or protein products are well known to those of skill in the art. Similarly, binding assays and reporter gene assays are similarly well known. Thus, e.g., U.S. Patent No. 5,559,410 discloses high throughput screening methods for proteins, U.S. Patent No. 5,585,639 discloses high throughput screening methods for nucleic acid binding (i.e., in arrays), while U.S. Patent Nos. 5,576,220 and 5,541,061 disclose high throughput methods of screening for ligand/antibody binding. Each of the above-cited patents is hereby incorporated by reference herein.
In addition, high throughput screening systems are commercially available (see, e.g., Zymark Corp., Hopkinton, MA; Air Technical Industries, Mentor, OH; Beckman Instruments, Inc. Fullerton, CA; Precision Systems, Inc., Natick, MA, etc.). These systems typically automate procedures, including sample and reagent pipetting, liquid dispensing, timed incubations, and final readings of the microplate in detector(s) appropriate for the assay. These configurable systems provide high throughput and rapid start up as well as a high degree of flexibility and customization. The manufacturers of such systems provide detailed protocols for various high throughput systems. Thus, e.g., Zymark Corp. provides technical bulletins describing screening systems for detecting the modulation of gene transcription, ligand binding, and the like.
In one embodiment, modulators are proteins, often naturally occurring proteins or fragments of naturally occurring proteins. Thus, e.g., cellular extracts containing proteins, or random or directed digests of proteinaceous cellular extracts, may be used. In this way libraries of proteins may be made for screening in the methods of the invention. Particularly preferred in this embodiment are libraries of bacterial, fungal, viral, and mammalian proteins, with the latter being preferred, and human proteins being especially preferred. Particularly useful test compound will be directed to the class of proteins to which the target belongs, e.g., substrates for enzymes or ligands and receptors.
In a preferred embodiment, modulators are peptides of from about 5 to about 30 amino acids, with from about 5 to about 20 amino acids being preferred, and from about 7 to about 15 being particularly preferred. The peptides may be digests of naturally occurring proteins as is outlined above, random peptides, or "biased" random peptides. By "randomized" or grammatical equivalents herein is meant that the nucleic acid or peptide consists of essentially random sequences of nucleotides and amino acids, respectively. Since these random peptides (or nucleic acids, discussed below) are often chemically synthesized, they may incorporate any nucleotide or amino acid at any position. The synthetic process can be designed to generate randomized proteins or nucleic acids, to allow the formation of all or most of the possible combinations over the length of the sequence, thus forming a library of randomized candidate bioactive proteinaceous agents. In one embodiment, the library is fully randomized, with no sequence preferences or constants at any position. In a preferred embodiment, the library is biased. That is, some positions within the sequence are either held constant, or are selected from a limited number of possibilities. In a preferred embodiment, the nucleotides or amino acid residues are randomized within a defined class, e.g., of hydrophobic amino acids, hydrophilic residues, sterically biased (either small or large) residues, towards the creation of nucleic acid binding domains, the creation of cysteines, for cross-linking, prolines for SH-3 domains, serines, threonines, tyrosines or histidines for phosphorylation sites, etc.
Modulators of metastatic breast cancer or metastatic lung cancer can also be nucleic acids, as defined above.
As described above generally for proteins, nucleic acid modulating agents may be naturally occurring nucleic acids, random nucleic acids, or "biased" random nucleic acids. Digests of procaryotic or eucaryotic genomes may be used as is outlined above for proteins.
In a preferred embodiment, the candidate compounds are organic chemical moieties, a wide variety of which are available in the literature.
After a candidate agent has been added and the cells allowed to incubate for some period of time, the sample containing a target sequence is analyzed. If required, the target sequence is prepared using known techniques. For example, the sample may be treated to lyse the cells, using known lysis buffers, electroporation, etc., with purification and/or amplification such as PCR performed as appropriate. For example, an in vitro transcription with labels covalently attached to the nucleotides is performed. Generally, the nucleic acids are labeled with biotin-FITC or PE, or with Cy-3 or Cy-5.
In a preferred embodiment, the target sequence is labeled with, e.g., a fluorescent, a chemiluminescent, a chemical, or a radioactive signal, to provide a means of detecting the target sequence's specific binding to a probe. The label also can be an enzyme, such as, alkaline phosphatase or horseradish peroxidase, which when provided with an appropriate substrate produces a product that can be detected. Alternatively, the label can be a labeled compound or small molecule, such as an enzyme inhibitor, that binds but is not catalyzed or altered by the enzyme. The label also can be a moiety or compound, such as, an epitope tag or biotin which specifically binds to streptavidin. For the example of biotin, the streptavidin is labeled as described above, thereby, providing a detectable signal for the bound target sequence. Unbound labeled streptavidin is typically removed prior to analysis.
Nucleic acid assays can be direct hybridization assays or can comprise "sandwich assays", which include the use of multiple probes, as is generally outlined in U.S. Patent Nos. 5,681,702, 5,597,909, 5,545,730, 5,594,117, 5,591,584, 5,571,670, 5,580,731, 5,571,670, 5,591,584, 5,624,802, 5,635,352, 5,594,118, 5,359,100, 5,124,246 and 5,681,697, all of which are hereby incorporated by reference herein. In this embodiment, in general, the target nucleic acid is prepared as outlined above, and then added to the biochip comprising a plurality of nucleic acid probes, under conditions that allow the formation of a hybridization complex.
A variety of hybridization conditions may be used in the present invention, including high, moderate and low stringency conditions as outlined above. The assays are generally run under stringency conditions which allow formation of the label probe hybridization complex only in the presence of target. Stringency can be controlled by altering a step parameter that is a thermodynamic variable, including, but not limited to, temperature, formamide concentration, salt concentration, chaotropic salt concentration, pH, organic solvent concentration, etc.
These parameters may also be used to control non-specific binding, as is generally outlined in U.S. Patent No. 5,681 ,697, which is hereby incorporated by reference herein. Thus, it may be desirable to perform certain steps at higher stringency conditions to reduce non-specific binding.
The reactions outlined herein may be accomplished in a variety of ways. Components of the reaction may be added simultaneously, or sequentially, in different orders, with preferred embodiments outlined below. In addition, the reaction may include a variety of other reagents. These include salts, buffers, neutral proteins, e.g., albumin, detergents, etc. which may be used to facilitate optimal hybridization and detection, and/or reduce nonspecific or background interactions. Reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may also be used as appropriate, depending on the sample preparation methods and purity of the target. The assay data are analyzed to determine the expression levels, and changes in expression levels as between states, of individual genes, forming a gene expression profile.
Screens are performed to identify modulators of the metastatic breast cancer or metastatic lung cancer phenotype. In one embodiment, screening is performed to identify modulators that can induce or suppress a particular expression profile, thus preferably generating the associated phenotype. In another embodiment, e.g., for diagnostic applications, having identified differentially expressed genes important in a particular state, screens can be performed to identify modulators that alter expression of individual genes. In an another embodiment, screening is performed to identify modulators that alter a biological function of the expression product of a differentially expressed gene. Again, having identified the importance of a gene in a particular state, screens are performed to identify agents that bind and/or modulate the biological activity of the gene product, or evaluate genetic polymorphisms. Genes can be screened for those that are induced in response to a candidate agent.
After identifying a modulator based upon its ability to suppress a metastatic breast cancer or metastatic lung cancer expression pattern leading to a normal expression pattern, or to modulate a single metastatic breast cancer or metastatic lung cancer gene expression profile so as to mimic the expression of the gene from normal tissue, a screen as described above can be performed to identify genes that are specifically modulated in response to the agent. Comparing expression profiles between normal tissue and agent treated metastatic breast cancer or metastatic lung cancer tissue reveals genes that are not expressed in normal tissue or metastatic breast cancer or metastatic lung cancer tissue, but are expressed in agent treated tissue. These agent-specific sequences can be identified and used by methods described herein for metastatic breast cancer or metastatic lung cancer genes or proteins. In particular these sequences and the proteins they encode find use in marking or identifying agent treated cells. In addition, antibodies can be raised against the agent induced proteins and used to target novel therapeutics to the treated metastatic breast cancer or metastatic lung cancer tissue sample. Thus, in one embodiment, a test compound is administered to a population of , metastatic breast cancer or metastatic lung cancer cells, that have an associated metastatic breast cancer or metastatic lung cancer expression profile. By "administration" or "contacting" herein is meant that the candidate agent is added to the cells in such a manner as to allow the agent to act upon the cell, whether by uptake and intracellular action, or by action at the cell surface. In some embodiments, nucleic acid encoding a proteinaceous candidate agent (i.e., a peptide) may be put into a viral construct such as an adenoviral or retroviral construct, and added to the cell, such that expression of the peptide agent is accomplished, e.g., PCT US97/01019. Regulatable gene therapy systems can also be used. Once the test compound has been administered to the cells, the cells can be washed if desired and are allowed to incubate under preferably physiological conditions for some period of time. The cells are then harvested and a new gene expression profile is generated, as outlined herein.
Thus, e.g., metastatic breast cancer or metastatic lung cancer tissue may be screened for agents that modulate, e.g., induce or suppress the metastatic breast cancer or metastatic lung cancer phenotype. A change in at least one gene, preferably many, of the expression profile indicates that the agent has an effect on metastatic breast cancer or metastatic lung cancer activity. By defining such a signature for the metastatic breast cancer or metastatic lung cancer phenotype, screens for new drags that alter the phenotype can be devised. With this approach, the drug target need not be known and need not be represented in the original expression screening platform, nor does the level of transcript for the target protein need to change.
Measure of metastatic breast cancer or metastatic lung cancer polypeptide activity, or of metastatic breast cancer or metastatic lung cancer or the metastatic breast cancer or metastatic lung cancer phenotype can be performed using a variety of assays. For example, the effects of the test compounds upon the function of the metastatic polypeptides can be measured by examining parameters described above. A suitable physiological change that affects activity can be used to assess the influence of a test compound on the polypeptides of this invention. When the functional consequences are determined using intact cells or animals, one can also measure a variety of effects such as, in the case of metastatic breast cancer or metastatic lung cancer associated with tumors, tumor growth, tumor metastasis, neovascularization, hormone release, transcriptional changes to both known and uncharacterized genetic markers (e.g., northern blots), changes in cell metabolism such as cell growth or pH changes, and changes in intracellular second messengers such as cGMP. In the assays of the invention, mammalian metastatic breast cancer or metastatic lung cancer polypeptide is typically used, e.g., mouse, preferably human.
To perform assays in intact animals where the breast or lung cancer has metastasized to the brain, it may be necessary to provide special treatments to facilitate crossing of the blood brain barrier by the metastatic cancer modulator or therapeutic. Any method known in the art can be used to achieve this objective.
Assays to identify compounds with modulating activity can be performed in vitro. For example, a metastatic breast cancer or metastatic lung cancer polypeptide is first contacted with a potential modulator and incubated for a suitable amount of time, e.g., from 0.5 to 48 hours. In one embodiment, the metastatic breast cancer or metastatic lung cancer polypeptide levels are determined in vitro by measuring the level of protein or mRNA. The level of protein is measured using immunoassays such as western blotting, ELISA and the like with an antibody that selectively binds to the metastatic breast cancer or metastatic lung cancer polypeptide or a fragment thereof. For measurement of mRNA, amplification, e.g., using PCR, LCR, or hybridization assays, e.g., northern hybridization, RNAse protection, dot blotting, are prefened. The level of protein or mRNA is detected using directly or indirectly labeled detection agents, e.g., fluorescently or radioactively labeled nucleic acids, radioactively or enzymatically labeled antibodies, and the like, as described herein.
Alternatively, a reporter gene system can be devised using the metastatic breast cancer or metastatic lung cancer protein promoter operably linked to a reporter gene such as luciferase, green fluorescent protein, CAT, or /3-gal. The reporter construct is typically transfected into a cell. After treatment with a potential modulator, the amount of reporter gene transcription, translation, or activity is measured according to standard techniques known to those of skill in the art. In a preferred embodiment, as outlined above, screens may be done on individual genes and gene products (proteins). That is, having identified a particular differentially expressed gene as important in a particular state, screening of modulators of the expression of the gene or the gene product itself can be done. The gene products of differentially expressed genes are sometimes referred to herein as "metastatic breast cancer or metastatic lung cancer proteins." The metastatic breast cancer or metastatic lung cancer protem may be a fragment, or alternatively, be the full length protein to a fragment shown herein.
In one embodiment, screening for modulators of expression of specific genes is performed. Typically, the expression of only one or a few genes are evaluated. In another embodiment, screens are designed to first find compounds that bind to differentially expressed proteins. These compounds are then evaluated for the ability to modulate differentially expressed activity. Moreover, once initial candidate compounds are identified, variants can be further screened to better evaluate stracture activity relationships.
In a preferred embodiment, binding assays are done. In general, purified or isolated gene product is used; that is, the gene products of one or more differentially expressed nucleic acids are made. For example, antibodies are generated to the protein gene products, and standard immunoassays are ran to determine the amount of protein present. Alternatively, cells comprising the metastatic breast cancer or metastatic lung cancer proteins can be used in the assays.
Thus, in a preferred embodiment, the methods comprise combining a metastatic breast cancer or metastatic lung cancer protein and a candidate compound, and determining the binding of the compound to the metastatic breast cancer or metastatic lung cancer protein. Preferred embodiments utilize the human metastatic breast cancer or metastatic lung cancer protein, although other mammalian proteins may also be used, e.g., for the development of animal models of human disease. In some embodiments, as outlined herein, variant or derivative metastatic breast cancer or metastatic lung cancer proteins may be used.
Generally, in a prefened embodiment of the methods herein, the metastatic breast cancer or metastatic lung cancer protein or the candidate agent is non-diffusably bound to an insoluble support having isolated sample receiving areas (e.g., a microtiter plate, an anay, etc.). The insoluble supports may be made of any composition to which the compositions can be bound, is readily separated from soluble material, and is otherwise compatible with the overall method of screening. The surface of such supports may be solid or porous and of any convenient shape. Examples of suitable insoluble supports include microtiter plates, anays, membranes and beads. These are typically made of glass, plastic (e.g., polystyrene), polysaccharides, nylon or nitrocellulose, TEFLON®, etc. Microtiter plates and anays are especially convenient because a large number of assays can be carried out simultaneously, using small amounts of reagents and samples. The particular manner of binding of the composition is not crucial so long as it is compatible with the reagents and overall methods of the invention, maintains the activity of the composition and is nondiffusable. Prefened methods of binding include the use of antibodies (which do not sterically block either the ligand binding site or activation sequence when the protem is bound to the support), direct binding to "sticky" or ionic supports, chemical crosslinking, the synthesis of the protein or agent on the surface, etc. Following binding of the protein or agent, excess unbound material is removed by washing. The sample receiving areas may then be blocked through incubation with bovine serum albumin (BSA), casein or other innocuous protein or other moiety.
In a prefened embodiment, the metastatic breast cancer or metastatic lung cancer protein is bound to the support, and a test compound is added to the assay. Alternatively, the candidate agent is bound to the support and the metastatic breast cancer or metastatic lung cancer protein is added. Novel binding agents include specific antibodies, non-natural binding agents identified in screens of chemical libraries, peptide analogs, etc. Of particular interest are screening assays for agents that have a low toxicity for human cells. A wide variety of assays may be used for this purpose, including labeled in vitro protein-protein binding assays, electrophoretic mobility shift assays, immunoassays for protein binding, functional assays (phosphorylation assays, etc.) and the like.
The determination of the binding of the test modulating compound to the metastatic breast cancer or metastatic lung cancer protein may be done in a number of ways. In a prefened embodiment, the compound is labeled, and binding determined directly, e.g., by attaching all or a portion of the metastatic breast cancer or metastatic lung cancer protein to a solid support, adding a labeled candidate agent (e.g., a fluorescent label), washing off excess reagent, and determining whether the label is present on the solid support. Various blocking and washing steps may be utilized as appropriate.
In some embodiments, only one of the components is labeled, e.g., the proteins (or proteinaceous candidate compounds) can be labeled. Alternatively, more than one component can be labeled with different labels, e.g., 125I for the proteins and a fluorophor for the compound. Proximity reagents, e.g., quenching or energy transfer reagents are also useful.
In one embodiment, the binding of the test compound is determined by competitive binding assay. The competitor is a binding moiety known to bind to the target molecule (i.e., a metastatic breast cancer or metastatic lung cancer protein), such as an antibody, peptide, binding partner, ligand, etc. Under certain circumstances, there may be competitive binding between the compound and the binding moiety, with the binding moiety displacing the compound. In one embodiment, the test compound is labeled. Either the compound, or the competitor, or both, is added first to the protein for a time sufficient to allow binding, if present. Incubations may be performed at a temperature which facilitates optimal activity, typically between 4 and 40°C. Incubation periods are typically optimized, e.g., to facilitate rapid high throughput screening. Typically between 0.1 and 1 hour will be sufficient. Excess reagent is generally removed or washed away. The second component is then added, and the presence or absence of the labeled component is followed, to indicate binding.
In a prefened embodiment, the competitor is added first, followed by the test compound. Displacement of the competitor is an indication that the test compound is binding to the metastatic breast cancer or metastatic lung cancer protein and thus is capable of binding to, and potentially modulating, the activity of the metastatic breast cancer or metastatic lung cancer protein. In this embodiment, either component can be labeled. Thus, e.g., if the competitor is labeled, the presence of label in the wash solution indicates displacement by the agent. Alternatively, if the test compound is labeled, the presence of the label on the support indicates displacement.
In an alternative embodiment, the test compound is added first, with incubation and washing, followed by the competitor. The absence of binding by the competitor may indicate that the test compound is bound to the metastatic breast cancer or metastatic lung cancer protein with a higher affinity. Thus, if the test compound is labeled, the presence of the label on the support, coupled with a lack of competitor binding, may indicate that the test compound is capable of binding to the metastatic breast cancer or metastatic lung cancer protein.
In a prefened embodiment, the methods comprise differential screening to identity agents that are capable of modulating the activity of the metastatic breast cancer or metastatic lung cancer proteins. In this embodiment, the methods comprise combining a metastatic breast cancer or metastatic lung cancer protein and a competitor in a first sample. A second sample comprises a test compound, a metastatic breast cancer or metastatic lung cancer protein, and a competitor. The binding of the competitor is determined for both samples, and a change, or difference in binding between the two samples indicates the presence of an agent capable of binding to the metastatic breast cancer or metastatic lung cancer protein and potentially modulating its activity. That is, if the binding of the competitor is different in the second sample relative to the first sample, the agent is capable of binding to the metastatic breast cancer or metastatic lung cancer protein.
Alternatively, differential screening is used to identify drag candidates that bind to the native metastatic breast cancer or metastatic lung cancer protem, but cannot bind to modified metastatic breast cancer or metastatic lung cancer proteins. The stracture of the metastatic breast cancer or metastatic lung cancer protein may be modeled, and used in rational drag design to synthesize agents that interact with that site. Drag candidates that affect the activity of a metastatic breast cancer or metastatic lung cancer protein are also identified by screening drags for the ability to either enhance or reduce the activity of the protein.
Positive controls and negative controls may be used in the assays. Preferably control and test samples are performed in at least triplicate to obtain statistically significant results. Incubation of all samples is for a time sufficient for the binding of the agent to the protein. Following incubation, samples are washed free of non-specifically bound material and the amount of bound, generally labeled agent determined. For example, where a radiolabel is employed, the samples may be counted in a scintillation counter to determine the amount of bound compound.
A variety of other reagents may be included in the screening assays. These include reagents like salts, neutral proteins, e.g., albumin, detergents, etc. which may be used to facilitate optimal protein-protein binding and/or reduce non-specific or background interactions. Also reagents that otherwise improve the efficiency of the assay, such as protease inhibitors, nuclease inhibitors, anti-microbial agents, etc., may be used. The mixture of components may be added in an order that provides for the requisite binding. In a prefened embodiment, the invention provides methods for screening for a compound capable of modulating the activity of a metastatic breast cancer or metastatic lung cancer protein. The methods comprise adding a test compound, as defined above, to a cell comprising metastatic breast cancer or metastatic lung cancer proteins. Prefened cell types include almost any cell. The cells contain a recombinant nucleic acid that encodes a metastatic breast cancer or metastatic lung cancer protein. In a prefened embodiment, a library of candidate agents are tested on a plurality of cells.
In one aspect, the assays are evaluated in the presence or absence or previous or subsequent exposure of physiological signals, e.g., hormones, antibodies, peptides, antigens, cytokines, growth factors, action potentials, pharmacological agents including chemotherapeutics, radiation, carcinogenics, or other cells (i.e. cell-cell contacts). In another example, the determinations are determined at different stages of the cell cycle process.
In this way, compounds that modulate metastatic breast cancer or metastatic lung cancer agents are identified. Compounds with pharmacological activity are able to enhance or interfere with the activity of the metastatic breast cancer or metastatic lung cancer protein. Once identified, similar structures are evaluated to identify critical structural feature of the compound.
In one embodiment, a method of inhibiting metastatic breast cancer or metastatic lung cancer cell division is provided. The method comprises administration of a metastatic breast cancer or metastatic lung cancer inhibitor. In another embodiment, a method of inhibiting metastatic breast cancer or metastatic lung cancer is provided. The method comprises administration of a metastatic breast cancer or metastatic lung cancer inhibitor. In a further embodiment, methods of treating cells or individuals with metastatic breast cancer or metastatic lung cancer are provided. The method comprises administration of a metastatic breast cancer or metastatic lung cancer inhibitor.
A variety of cell growth, proliferation, and metastasis assays are known to those of skill in the art, as described below.
Soft agar growth or colony formation in suspension Normal cells require a solid substrate to attach and grow. When the cells are transformed, they lose this phenotype and grow detached from the substrate. For example, transformed cells can grow in stiπed suspension culture or suspended in semi-solid media, such as semi-solid or soft agar. The transformed cells, when transfected with tumor suppressor genes, regenerate normal phenotype and require a solid substrate to attach and grow. Soft agar growth or colony formation in suspension assays can be used to identify modulators of metastatic breast cancer or metastatic lung cancer sequences, which when expressed in host cells, inhibit abnormal cellular proliferation and transformation. A therapeutic compound would reduce or eliminate the host cells' ability to grow in stiπed suspension culture or suspended in semi-solid media, such as semi-solid or soft.
Techniques for soft agar growth or colony formation in suspension assays are described in Freshney, Culture of Animal Cells a Manual of Basic Technique (3rd ed., 1994), herein incorporated by reference. See also, the methods section of Garkavtsev et al. (1996), supra, herein incorporated by reference.
Contact inhibition and density limitation of growth Normal cells typically grow in a flat and organized pattern in a petri dish until they touch other cells. When the cells touch one another, they are contact inhibited and stop growing. When cells are transformed, however, the cells are not contact inhibited and continue to grow to high densities in disorganized foci. Thus, the transformed cells grow to a higher saturation density than normal cells. This can be detected morphologically by the formation of a disoriented monolayer of cells or rounded cells in foci within the regular pattern of normal sunounding cells. Alternatively, labeling index with (3H)-thymidine at saturation density can be used to measure density limitation of growth. See Freshney (1994), supra. The transformed cells, when transfected with tumor suppressor genes, regenerate a normal phenotype and become contact inhibited and would grow to a lower density.
In this assay, labeling index with (3H)-thymidine at saturation density is a prefened method of measuring density limitation of growth. Transformed host cells are transfected with a metastatic breast cancer or metastatic lung cancer-associated sequence and are grown for 24 hours at saturation density in non-limiting medium conditions. The percentage of cells labeling with (3H)-thymidine is determined autoradiographically. See, Freshney (1994), supra.
Growth factor or serum dependence Transformed cells have a lower serum dependence than their normal counterparts
(see, e.g., Temin, J. Natl Cancer Insti. 37:167-175 (1966); Eagle et al, J. Exp. Med. 131 :836-879 (1970)); Freshney, supra. This is in part due to release of various growth factors by the transformed cells. Growth factor or serum dependence of transformed host cells can be compared with that of control. Tumor specific markers levels Tumor cells release an increased amount of certain factors (hereinafter "tumor specific markers") than their normal counterparts. For example, plasminogen activator (PA) is released from human glioma at a higher level than from normal brain cells (see, e.g.,
Gullino, Angiogenesis, tumor vascularization, and potential interference with tumor growth. in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985)). Similarly, Tumor angiogenesis factor (TAF) is released at a higher level in tumor cells than their normal counterparts. See, e.g., Folkman, Angiogenesis and Cancer, Sem Cancer Biol. (1992)). Various techniques which measure the release of these factors are described in
Freshney (1994), supra. Also, see, Unkless et al. , J. Biol. Chem. 249:4295-4305 (1974); Strickland & Beers, J. Biol. Chem. 251:5694-5702 (1976); Whur et al, Br. J. Cancer 42:305- 312 (1980); Gullino, Angiogenesis, tumor vascularization, and potential interference with tumor growth, in Biological Responses in Cancer, pp. 178-184 (Mihich (ed.) 1985); Freshney Anticancer Res. 5:111-130 (1985).
Invasiveness into Matrigel The degree of invasiveness into Matrigel or some other extracellular matrix constituent can be used as an assay to identify compounds that modulate metastatic breast cancer or metastatic lung cancer-associated sequences. Tumor cells exhibit a good coπelation between malignancy and invasiveness of cells into Matrigel or some other extracellular matrix constituent. In this assay, tumorigenic cells are typically used as host cells. Expression of a tumor suppressor gene in these host cells would decrease invasiveness of the host cells. Techniques described in Freshney (1994), supra, can be used. Briefly, the level of invasion of host cells can be measured by using filters coated with Matrigel or some other extracellular matrix constituent. Penetration into the gel, or through to the distal side of the filter, is rated as invasiveness, and rated histologically by number of cells and distance moved, or by prelabeling the cells with 125I and counting the radioactivity on the distal side of the filter or bottom of the dish. See, e.g., Freshney (1984), supra.
Tumor growth in vivo Effects of metastatic breast cancer or metastatic lung cancer-associated sequences on cell growth can be tested in fransgenic or immune-suppressed mice. Knock-out fransgenic mice can be made, in which the metastatic breast cancer or metastatic lung cancer gene is disrupted or in which a metastatic breast cancer or metastatic lung cancer gene is inserted. Knock-out fransgenic mice can be made by insertion of a marker gene or other heterologous gene into the endogenous metastatic breast cancer or metastatic lung cancer gene site in the mouse genome via homologous recombination. Such mice can also be made by substituting the endogenous metastatic breast cancer or metastatic lung cancer gene with a mutated version of the metastatic breast cancer or metastatic lung cancer gene, or by mutating the endogenous metastatic breast cancer or metastatic lung cancer gene, e.g., by exposure to carcinogens. A DNA construct is introduced into the nuclei of embryonic stem cells. Cells containing the newly engineered genetic lesion are injected into a host mouse embryo, which is re-implanted into a recipient female. Some of these embryos develop into chimeric mice that possess germ cells partially derived from the mutant cell line. Therefore, by breeding the chimeric mice it is possible to obtain a new line of mice containing the introduced genetic lesion (see, e.g., Capecchi et al, Science 244:1288 (1989)). Chimeric targeted mice can be derived according to Hogan et al. , Manipulating the Mouse Embryo: A Laboratory Manual, Cold Spring Harbor Laboratory (1988) and Teratocarcinomas and Embryonic Stem Cells: A Practical Approach, Robertson, ed., IRL Press, Washington, D.C., (1987).
Alternatively, various immune-suppressed or immune-deficient host animals can be used. For example, genetically athymic "nude" mouse (see, e.g., Giovanella et al, J. Natl Cancer Inst. 52:921 (1974)), a SCID mouse, a thymectomized mouse, or an inadiated mouse (see, e.g., Bradley et al, Br. J. Cancer 38:263 (1978); Selby et al, Br. J. Cancer 41:52 (1980)) can be used as a host. Transplantable tumor cells (typically about 106 cells) injected into isogenic hosts will produce invasive tumors in a high proportions of cases, while normal cells of similar origin will not. In hosts which developed invasive tumors, cells expressing a metastatic breast cancer or metastatic lung cancer-associated sequences are injected subcutaneously. After a suitable length of time, preferably 4-8 weeks, tumor growth is measured (e.g., by volume or by its two largest dimensions) and compared to the control. Tumors that have statistically significant reduction (using, e.g., Student's T test) are said to have inhibited growth. Additionally, human tumor cells expressing the genes of the invention may be injected into immune compromised animals. Growth of these tumors, or xenografts, is compared to growth of similar human tumor cell that do not express the genes of the invention. These animals may also be used to binding assays and efficacy studies for therapeutic compounds that modulate metastatic breast cancer or metastatic lung cancer, such as antibodies or small molecules.
Polynucleotide modulators of metastatic breast cancer or metastatic lung cancer Antisense Polynucleotides
In certain embodiments, the activity of a metastatic breast cancer or metastatic lung cancer-associated protein is downregulated, or entirely inhibited, by the use of antisense polynucleotide, i.e., a nucleic acid complementary to, and which can preferably hybridize specifically to, a coding mRNA nucleic acid sequence, e.g., a metastatic breast cancer or metastatic lung cancer protein mRNA, or a subsequence thereof. Binding of the antisense polynucleotide to the mRNA reduces the translation and/or stability of the mRNA.
In the context of this invention, antisense polynucleotides can comprise naturally- occurring nucleotides, or synthetic species formed from naturally-occurring subunits or their close homologs. Antisense polynucleotides may also have altered sugar moieties or inter- sugar linkages. Exemplary among these are the phosphorothioate and other sulfur containing species which are known for use in the art. Analogs are comprehended by this invention so long as they function effectively to hybridize with the metastatic breast cancer or metastatic lung cancer protein mRNA. See, e.g., Isis Pharmaceuticals, Carlsbad, CA; Sequitor, Inc., Natick, MA. Such antisense polynucleotides can readily be synthesized using recombinant means, or can be synthesized in vitro. Equipment for such synthesis is sold by several vendors, including Applied Biosystems (Norwalk, CT). The preparation of other oligonucleotides such as phosphorothioates and alkylated derivatives is also well known to those of skill in the art. Antisense molecules as used herein include antisense or sense oligonucleotides.
Sense oligonucleotides can, e.g., be employed to block transcription by binding to the anti- sense strand. The antisense and sense oligonucleotide comprise a single-stranded nucleic acid sequence (either RNA or DNA) capable of binding to target mRNA (sense) or DNA (antisense) sequences for metastatic breast cancer or metastatic lung cancer molecules. A prefened antisense molecule is for a metastatic breast cancer or metastatic lung cancer sequence selected from those listed in Tables 1 A-12C, or for a ligand or activator thereof. Antisense or sense oligonucleotides, according to the present invention, comprise a fragment generally at least about 14 nucleotides, preferably from about 14 to 30 nucleotides. The ability to derive an antisense or a sense oligonucleotide, based upon a cDNA sequence encoding a given protein is described in, e.g., Stein & Cohen (Cancer Res. 48:2659 (1988 and van der Krol et al. (BioTechniques 6:958 (1988)).
Ribozymes In addition to antisense polynucleotides, ribozymes can be used to target and inhibit transcription of metastatic breast cancer or metastatic lung cancer-associated nucleotide sequences. A ribozyme is an RNA molecule that catalytically cleaves other RNA molecules. Different kinds of ribozymes have been described, including group I ribozymes, hammerhead ribozymes, hairpin ribozymes, RNase P, and axhead ribozymes (see, e.g., Castanotto et al, Adv. in Pharmacology 25: 289-317 (1994) for a general review of the properties of different ribozymes).
The general features of hairpin ribozymes are described, e.g., in Hampel et al, Nucl Acids Res. 18:299-304 (1990); European Patent Publication No. 0 360 257; U.S. Patent No. 5,254,678, which is hereby incorporated by reference herein.. Methods of preparing are well known to those of skill in the art (see, e.g., WO 94/26877; Ojwang et al, Proc. Natl. Acad. Sci. USA 90:6340-6344 (1993); Yamada et al, Human Gene Therapy 1:39-45 (1994); Leavitt et al, Proc. Natl. Acad. Sci. USA 92:699-703 (1995); Leavitt et al, Human Gene Therapy 5:1151-120 (1994); and Yamada et al, Virology 205: 121-126 (1994)).
Polynucleotide modulators of metastatic breast cancer or metastatic lung cancer may be introduced into a cell containing the target nucleotide sequence by formation of a conjugate with a ligand binding molecule, as described in WO 91/04753. Suitable ligand binding molecules include, but are not limited to, cell surface receptors, growth factors, other cytokines, or other ligands that bind to cell surface receptors. Preferably, conjugation of the ligand binding molecule does not substantially interfere with the ability of the ligand binding molecule to bind to its conesponding molecule or receptor, or block entry of the sense or antisense oligonucleotide or its conjugated version into the cell. Alternatively, a polynucleotide modulator of metastatic breast cancer or metastatic lung cancer may be introduced into a cell containing the target nucleic acid sequence, e.g., by formation of an polynucleotide-lipid complex, as described in WO 90/10448. It is understood that the use of antisense molecules or knock out and knock in models may also be used in screening assays as discussed above, in addition to methods of treatment.
Thus, in one embodiment, methods of modulating metastatic breast cancer or metastatic lung cancer in cells or organisms are provided. In one embodiment, the methods comprise administering to a cell an anti-metastatic breast cancer or metastatic lung cancer antibody that reduces or eliminates the biological activity of an endogenous metastatic breast cancer or metastatic lung cancer protein. Alternatively, the methods comprise administering to a cell or organism a recombinant nucleic acid encoding a metastatic breast cancer or metastatic lung cancer protem. This may be accomplished in any number of ways. In a prefened embodiment, e.g., when the metastatic breast cancer or metastatic lung cancer sequence is down-regulated in metastatic breast cancer or metastatic lung cancer, such state may be reversed by increasing the amount of metastatic breast cancer or metastatic lung cancer gene product in the cell. This can be accomplished, e.g., by overexpressing the endogenous metastatic breast cancer or metastatic lung cancer gene or administering a gene encoding the metastatic breast cancer or metastatic lung cancer sequence, using known gene- therapy techniques. In a prefened embodiment, the gene therapy techniques include the incorporation of the exogenous gene using enhanced homologous recombination (EHR), e.g., as described in PCT/US93/03868, hereby incorporated by reference in its entirety. Alternatively, e.g., when the metastatic breast cancer or metastatic lung cancer sequence is up-regulated in metastatic breast cancer or metastatic lung cancer, the activity of the endogenous metastatic breast cancer or metastatic lung cancer gene is decreased, e.g., by the administration of a metastatic breast cancer or metastatic lung cancer antisense nucleic acid. In one embodiment, the metastatic breast cancer or metastatic lung cancer proteins of the present invention may be used to generate polyclonal and monoclonal antibodies to metastatic breast cancer or metastatic lung cancer proteins. Similarly, the metastatic breast cancer or metastatic lung cancer proteins can be coupled, using standard technology, to affinity chromatography columns. These columns may then be used to purify metastatic breast cancer or metastatic lung cancer antibodies useful for production, diagnostic, or therapeutic purposes. In a prefened embodiment, the antibodies are generated to epitopes unique to a metastatic breast cancer or metastatic lung cancer protein; that is, the antibodies show little or no cross-reactivity to other proteins. The metastatic breast cancer or metastatic lung cancer antibodies may be coupled to standard affinity chromatography columns and used to purify metastatic breast cancer or metastatic lung cancer proteins. The antibodies may also be used as blocking polypeptides, as outlined above, since they will specifically bind to the metastatic breast cancer or metastatic lung cancer protein. Methods of identifying variant metastatic breast cancer or metastatic lung cancer- associated sequences
Without being bound by theory, expression of various metastatic breast cancer or metastatic lung cancer sequences is conelated with metastatic breast cancer or metastatic lung cancer. Accordingly, disorders based on mutant or variant metastatic breast cancer or metastatic lung cancer genes may be determined. In one embodiment, the invention provides methods for identifying cells containing variant metastatic breast cancer or metastatic lung cancer genes, e.g., determining all or part of the sequence of at least one endogenous metastatic breast cancer or metastatic lung cancer genes in a cell. This may be accomplished using any number of sequencing techniques. In a prefened embodiment, the invention provides methods of identifying the metastatic breast cancer or metastatic lung cancer genotype of an individual, e.g., determining all or part of the sequence of at least one metastatic breast cancer or metastatic lung cancer gene of the individual. This is generally done in at least one tissue of the individual, and may include the evaluation of a number of tissues or different samples of the same tissue. The method may include comparing the sequence of the sequenced metastatic breast cancer or metastatic lung cancer gene to a known metastatic breast cancer or metastatic lung cancer gene, i.e., a wild-type gene.
The sequence of all or part of the metastatic breast cancer or metastatic lung cancer gene can then be compared to the sequence of a known metastatic breast cancer or metastatic lung cancer gene to determine if any differences exist. This can be done using any number of known homology programs, such as Bestfit, etc. In a prefened embodiment, the presence of a difference in the sequence between the metastatic breast cancer or metastatic lung cancer gene of the patient and the known metastatic breast cancer or metastatic lung cancer gene conelates with a disease state or a propensity for a disease state, as outlined herein. In a prefened embodiment, the metastatic breast cancer or metastatic lung cancer genes are used as probes to detennine the number of copies of the metastatic breast cancer or metastatic lung cancer gene in the genome.
In another prefened embodiment, the metastatic breast cancer or metastatic lung cancer genes are used as probes to determine the chromosomal localization of the metastatic breast cancer or metastatic lung cancer genes. Information such as chromosomal localization finds use in providing a diagnosis or prognosis in particular when chromosomal abnormalities such as translocations, and the like are identified in the metastatic breast cancer or metastatic lung cancer gene locus. Administration of pharmaceutical and vaccine compositions
In one embodiment, a therapeutically effective dose of a metastatic breast cancer or metastatic lung cancer protein or modulator thereof, is administered to a patient. By "therapeutically effective dose" herein is meant a dose that produces effects for which it is administered. The exact dose will depend on the purpose of the treatment, and will be ascertamable by one skilled in the art using known techniques (e.g., Ansel et al, Pharmaceutical Dosage Forms and Drug Delivery; Lieberman, Pharmaceutical Dosage Forms (vols. 1-3, 1992), Dekker, ISBN 0824770846, 082476918X, 0824712692, 0824716981; Lloyd, The Art, Science and Technology of Pharmaceutical Compounding (1999); and Pickar, Dosage Calculations (1999)). As is known in the art, adjustments for metastatic breast cancer or metastatic lung cancer degradation, systemic versus localized delivery, and rate of new protease synthesis, as well as the age, body weight, general health, sex, diet, time of administration, drag interaction and the severity of the condition may be necessary, and will be ascertainable with routine experimentation by those skilled in the art. A "patient" for the purposes of the present invention includes both humans and other animals, particularly mammals. Thus the methods are applicable to both human therapy and veterinary applications. In the preferred embodiment the patient is a mammal, preferably a primate, and in the most prefened embodiment the patient is human.
The administration of the metastatic breast cancer or metastatic lung cancer proteins and modulators thereof of the present invention can be done in a variety of ways as discussed above, including, but not limited to, orally, subcutaneously, intravenously, infranasally, fransdermally, intraperitoneally, intramuscularly, intrapulmonary, vaginally, rectally, or intraocularly. In some instances, e.g., in the treatment of wounds and inflammation, the metastatic breast cancer or metastatic lung cancer proteins and modulators may be directly applied as a solution or spray.
The pharmaceutical compositions of the present invention comprise a metastatic breast cancer or metastatic lung cancer protein in a form suitable for administration to a patient. In the prefened embodiment, the pharmaceutical compositions are in a water soluble form, such as being present as pharmaceutically acceptable salts, which is meant to include both acid and base addition salts. "Pharmaceutically acceptable acid addition salt" refers to those salts that retain the biological effectiveness of the free bases and that are not biologically or otherwise undesirable, formed with inorganic acids such as hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as acetic acid, propionic acid, glycolic acid, pyravic acid, oxalic acid, maleic acid, malonic acid, succinic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid and the like. "Pharmaceutically acceptable base addition salts" include those derived from inorganic bases such as sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum salts and the like. Particularly prefened are the ammonium, potassium, sodium, calcium, and magnesium salts. Salts derived from pharmaceutically acceptable organic non-toxic bases include salts of primary, secondary, and tertiary amines, substituted amines including naturally occurring substituted amines, cyclic amines and basic ion exchange resins, such as isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, and ethanolamine.
The pharmaceutical compositions may also include one or more of the following: carrier proteins such as serum albumin; buffers; fillers such as microcrystalline cellulose, lactose, corn and other starches; binding agents; sweeteners and other flavoring agents; coloring agents; and polyethylene glycol. The pharmaceutical compositions can be administered in a variety of unit dosage forms depending upon the method of administration. For example, unit dosage forms suitable for oral administration include, but are not limited to, powder, tablets, pills, capsules and lozenges. It is recognized that metastatic breast cancer or metastatic lung cancer protein modulators (e.g., antibodies, antisense constructs, ribozymes, small organic molecules, etc.) when administered orally, should be protected from digestion. It is also recognized that, after delivery to other sites in the body (e.g., circulatory system, lymphatic system, or the tumor site) the metastatic breast cancer or metastatic lung cancer modulators of the invention may need to be protected from excretion, hydrolisis, proteolytic digestion or modification, or detoxification by the liver. In all these cases, protection is typically accomplished either by complexing the molecule(s) with a composition to render it resistant to acidic and enzymatic hydrolysis, or by packaging the molecule(s) in an appropriately resistant carrier, such as a liposome or a protection barrier or by modifying the molecular size, weight, and/or charge of the modulator. Means of protecting agents from digestion degradation, and excretion are well known in the art. The compositions for administration will commonly comprise a metastatic breast cancer or metastatic lung cancer protein modulator dissolved in a pharmaceutically acceptable carrier, preferably an aqueous carrier. A variety of aqueous carriers can be used, e.g., buffered saline and the like. These solutions are sterile and generally free of undesirable matter. These compositions may be sterilized by conventional, well known sterilization techniques. The compositions may contain pharmaceutically acceptable auxiliary substances as required to approximate physiological conditions such as pH adjusting and buffering agents, toxicity adjusting agents and the like, e.g., sodium acetate, sodium chloride, potassium chloride, calcium chloride, sodium lactate and the like. The concentration of active agent in these formulations can vary widely, and will be selected primarily based on fluid volumes, viscosities, body weight and the like in accordance with the particular mode of administration selected and the patient's needs (e.g., Remington 's Pharmaceutical Science (15th ed., 1980) and Goodman & Gillman, 77ze Pharmacologial Basis ofTlierapeutics (Hardman et al., eds., 1996)). Thus, a typical pharmaceutical composition for intravenous administration would be about 0.1 to 10 mg per patient per day. Dosages from 0.1 up to about 100 mg per patient per day may be used, particularly when the drug is administered to a secluded site and not into the blood stream, such as into a body cavity or into a lumen of an organ. Substantially higher dosages are possible in topical administration. Actual methods for preparing parenterally administrable compositions will be known or apparent to those skilled in the art, e.g.,
Remington 's Pharmaceutical Science and Goodman and Gillman, The Pharmacologial Basis of Therapeutics, supra.
The compositions containing modulators of metastatic breast cancer or metastatic lung cancer proteins can be administered for therapeutic or prophylactic treatments. In therapeutic applications, compositions are administered to a patient suffering from a disease (e.g., a cancer) in an amount sufficient to cure or at least partially anest the disease and its complications. An amount adequate to accomplish this is defined as a "therapeutically effective dose." Amounts effective for this use will depend upon the severity of the disease and the general state of the patient's health. Single or multiple administrations of the compositions may be administered depending on the dosage and frequency as required and tolerated by the patient. In any event, the composition should provide a sufficient quantity of the agents of this invention to effectively treat the patient. An amount of modulator that is capable of preventing or slowing the development of cancer in a mammal is refened to as a "prophylactically effective dose." The particular dose required for a prophylactic treatment will depend upon the medical condition and history of the mammal, the particular cancer being prevented, as well as other factors such as age, weight, gender, administration route, efficiency, etc. Such prophylactic treatments may be used, e.g., in a mammal who has previously had cancer to prevent a recunence of the cancer, or in a mammal who is suspected of having a significant likelihood of developing cancer. It will be appreciated that the present metastatic breast cancer or metastatic lung cancer protein-modulating compounds can be administered alone or in combination with additional metastatic breast cancer or metastatic lung cancer modulating compounds or with other therapeutic agent, e.g., other anti-cancer agents or treatments. In numerous embodiments, one or more nucleic acids, e.g., polynucleotides comprising nucleic acid sequences set forth in Tables 1 A-12C, such as antisense polynucleotides or ribozymes, will be introduced into cells, in vitro or in vivo. The present invention provides methods, reagents, vectors, and cells useful for expression of metastatic breast cancer or metastatic lung cancer-associated polypeptides and nucleic acids using in vitro (cell-free), ex vivo or in vivo (cell or organism-based) recombinant expression systems. The particular procedure used to introduce the nucleic acids into a host cell for expression of a protein or nucleic acid is application specific. Many procedures for introducing foreign nucleotide sequences into host cells may be used. These include the use of calcium phosphate transfection, spheroplasts, electroporation, liposomes, microinjection, plasma vectors, viral vectors and any of the other well known methods for introducing cloned genomic DNA, cDNA, synthetic DNA or other foreign genetic material into a host cell (see, e.g., Berger & Kimmel, Guide to Molecular Cloning Techniques, Methods in Enzymology volume 152 (Berger), Ausubel et al, eds., Current Protocols (supplemented through 1999), and Sambrook et al, Molecular Cloning - A Laboratoiy Manual (2nd ed., Vol. 1-3, 1989. In a prefened embodiment, metastatic breast cancer or metastatic lung cancer proteins and modulators are administered as therapeutic agents, and can be formulated as outlined above. Similarly, metastatic breast cancer or metastatic lung cancer genes (including both the full-length sequence, partial sequences, or regulatory sequences of the metastatic breast cancer or metastatic lung cancer coding regions) can be administered in a gene therapy application. These metastatic breast cancer or metastatic lung cancer genes can include antisense applications, either as gene therapy (i.e., for incorporation into the genome) or as antisense compositions, as will be appreciated by those in the art.
Metastatic breast cancer or metastatic lung cancer polypeptides and polynucleotides can also be administered as vaccine compositions to stimulate HTL, CTL and antibody responses.. Such vaccine compositions can include, e.g., lipidated peptides (see, e.g.,Vitiello, et al, J. Gin. Invest. 95:341 (1995)), peptide compositions encapsulated in poly(DL-lactide- co-glycolide) ("PLG") microspheres (see, e.g., Eldridge, et al, Molec. Immunol. 28:287-294, (1991); Alonso et al, Vaccine 12:299-306 (1994); Jones et al, Vaccine 13:675-681 (1995)), peptide compositions contained in immune stimulating complexes (ISCOMS) (see, e.g., Takahashi et al, Nature 344:873-875 (1990); Hu et al, Gin Exp Immunol. 113:235-243 (1998)), multiple antigen peptide systems (MAPs) (see, e.g., Tarn, Proc. Natl. Acad. Sci. U.S.A. 85:5409-5413 (1988); Tarn, J. Immunol. Methods 196:17-32 (1996)), peptides formulated as multivalent peptides; peptides for use in ballistic delivery systems, typically crystallized peptides, viral delivery vectors (Perkus, et al, In: Concepts in vaccine development (Kaufmann, ed., p. 379, 1996); Chakrabarti, et al, Nature 320:535 (1986); Hu et al, Nature 320:537 (1986); Kieny, et al, AIDS Bio/Technology 4:790 (1986); Top et al, J. Infect. Dis. 124:148 (1971); Chanda et al, Virology 175:535 (1990)), particles of viral or synthetic origin (see, e.g., Kofler et al, J. Immunol. Methods. 192:25 (1996); Eldridge et al, Sem. Hematol. 30: 16 (1993); Falo et al, Nature Med. 7:649 (1995)), adjuvants (Wanen et al, Annu. Rev. Immunol. 4:369 (1986); Gupta et al, Vaccine 11:293 (1993)), liposomes (Reddy et al, J. Immunol 148:1585 (1992); Rock, Immunol. Today 17:131 (1996)), or, naked or particle absorbed cDNA (Ulmer, et al, Science 259:1745 (1993); Robinson et ah, Vaccine 11 :957 (1993); Shiver et al, In: Concepts in vaccine development (Kaufmann, ed., p. 423, 1996); Cease & Berzofsky, Annu. Rev. Immunol. 12:923 (1994) and Eldridge et al, Sem. Hematol. 30:16 (1993)). Toxin-targeted delivery technologies, also known as receptor mediated targeting, such as those of Avant Immunotherapeutics, Inc. (Needham, Massachusetts) may also be used.
Vaccine compositions often include adjuvants. Many adjuvants contain a substance designed to protect the antigen from rapid catabolism, such as aluminum hydroxide or mineral oil, and a stimulator of immune responses, such as lipid A, Bortadella pertussis or Mycobacterium tuberculosis derived proteins. Certain adjuvants are commercially available as, e.g., Freund's Incomplete Adjuvant and Complete Adjuvant (Difco Laboratories, Detroit, MI); Merck Adjuvant 65 (Merck and Company, Inc., Rahway, NJ); AS-2 (SmithKline Beecham, Philadelphia, PA); aluminum salts such as aluminum hydroxide gel (alum) or aluminum phosphate; salts of calcium, iron or zinc; an insoluble suspension of acylated tyrosine; acylated sugars; cationically or anionically derivatized polysaccharides; polyphosphazenes; biodegradable microspheres; monophosphoryl lipid A and quil A. Cytokines, such as GM-CSF, interleukin-2, -7, -12, and other like growth factors, may also be used as adjuvants.
Vaccines can be administered as nucleic acid compositions wherein DNA or RNA encoding one or more of the polypeptides, or a fragment thereof, is administered to a patient. This approach is described, for instance, in Wolff et. al, Science 247:1465 (1990) as well as U.S. Patent Nos. 5,580,859; 5,589,466; 5,804,566; 5,739,118; 5,736,524; 5,679,647; WO 98/04720, each of which is hereby incorporated by reference herein.; and in more detail below. Examples of DNA-based delivery technologies include "naked DNA", facilitated (bupivicaine, polymers, peptide-mediated) delivery, cationic lipid complexes, and particle- mediated ("gene gun") or pressure-mediated delivery (see, e.g., U.S. Patent No. 5,922,687, which is hereby incorporated by reference herein.).
For therapeutic or prophylactic immunization purposes, the peptides of the invention can be expressed by viral or bacterial vectors. Examples of expression vectors include attenuated viral hosts, such as vaccinia or fowlpox. This approach involves the use of vaccinia virus, e.g., as a vector to express nucleotide sequences that encode metastatic breast cancer or metastatic lung cancer polypeptides or polypeptide fragments. Upon introduction into a host, the recombinant vaccinia virus expresses the immunogenic peptide, and thereby elicits an immune response. Vaccinia vectors and methods useful in immunization protocols are described in, e.g., U.S. Patent No. 4,722,848, which is hereby incorporated by reference herein.. Another vector is BCG (Bacille Calmette Guerin). BCG vectors are described in Stover et al, Nature 351:456-460 (1991). A wide variety of other vectors useful for therapeutic administration or immunization e.g., adeno and adeno-associated virus vectors, retroviral vectors, Salmonella typhi vectors, detoxified anthrax toxin vectors, and the like, will be apparent to those skilled in the art from the description herein (see, e.g., Shata et al, Mol Med Today 6:66-71 (2000); Shedlock et al, JLeukoc Biol 68:793-806 (2000); Hipp et al, In Vivo 14:571-85 (2000)).
Methods for the use of genes as DNA vaccines are well known, and include placing a metastatic breast cancer or metastatic lung cancer gene or portion of a metastatic breast cancer or metastatic lung cancer gene under the control of a regulatable promoter or a tissue- specific promoter for expression in a metastatic breast cancer or metastatic lung cancer patient. The metastatic breast cancer or metastatic lung cancer gene used for DNA vaccines can encode full-length metastatic breast cancer or metastatic lung cancer proteins, but more preferably encodes portions of the metastatic breast cancer or metastatic lung cancer proteins including peptides derived from the metastatic breast cancer or metastatic lung cancer protein. In one embodiment, a patient is immunized with a DNA vaccine comprising a plurality of nucleotide sequences derived from a metastatic breast cancer or metastatic lung cancer gene. For example, metastatic breast cancer or metastatic lung cancer-associated genes or sequence encoding subfragments of a metastatic breast cancer or metastatic lung cancer protein are introduced into expression vectors and tested for their immunogenicity in the context of Class I MHC and an ability to generate cytotoxic T cell responses. This procedure provides for production of cytotoxic T cell responses against cells which present antigen, including intracellular epitopes.
In a prefened embodiment, the DNA vaccines include a gene encoding an adjuvant molecule with the DNA vaccine. Such adjuvant molecules include cytokines that increase the immunogenic response to the metastatic breast cancer or metastatic lung cancer polypeptide encoded by the DNA vaccine. Additional or alternative adjuvants are available. In another prefened embodiment metastatic breast cancer or metastatic lung cancer genes find use in generating animal models of metastatic breast cancer or metastatic lung cancer. When the metastatic breast cancer or metastatic lung cancer gene identified is repressed or diminished in metastatic tissue, gene therapy technology, e.g., wherein antisense RNA directed to the metastatic breast cancer or metastatic lung cancer gene will also diminish or repress expression of the gene. Animal models of metastatic breast cancer or metastatic lung cancer find use in screening for modulators of a metastatic breast cancer or metastatic lung cancer-associated sequence or modulators of metastatic breast cancer or metastatic lung cancer. Similarly, fransgenic animal technology including gene knockout technology, e.g., as a result of homologous recombination with an appropriate gene targeting vector, will result in the absence or increased expression of the metastatic breast cancer or metastatic lung cancer protein. When desired, tissue-specific expression or knockout of the metastatic breast cancer or metastatic lung cancer protein may be necessary. It is also possible that the metastatic breast cancer or metastatic lung cancer protein is overexpressed in metastatic breast cancer or metastatic lung cancer. As such, fransgenic animals can be generated that overexpress the metastatic breast cancer or metastatic lung cancer protein. Depending on the desired expression level, promoters of various strengths can be employed to express the fransgene. Also, the number of copies of the integrated fransgene can be determined and compared for a determination of the expression level of the fransgene. Animals generated by such methods find use as animal models of metastatic breast cancer or metastatic lung cancer and are additionally useful in screening for modulators to treat metastatic breast cancer or metastatic lung cancer.
Kits for Use in Diagnostic and/or Prognostic Applications
For use in diagnostic, research, and therapeutic applications suggested above, kits are also provided by the invention. In the diagnostic and research applications such kits may include any or all of the following: assay reagents, buffers, metastatic breast cancer or metastatic lung cancer-specific nucleic acids or antibodies, hybridization probes and/or primers, antisense polynucleotides, ribozymes, dominant negative metastatic breast cancer or metastatic lung cancer polypeptides or polynucleotides, small molecules inhibitors of metastatic breast cancer or metastatic lung cancer-associated sequences etc. A therapeutic product may include sterile saline or another pharmaceutically acceptable emulsion and suspension base.
In addition, the kits may include instructional materials containing directions (i.e., protocols) for the practice of the methods of this invention. While the instructional materials typically comprise written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this invention. Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. Such media may include addresses to internet sites that provide such instructional materials.
The present invention also provides for kits for screening for modulators of metastatic breast cancer or metastatic lung cancer-associated sequences. Such kits can be prepared from readily available materials and reagents. For example, such kits can comprise one or more of the following materials: a metastatic breast cancer or metastatic lung cancer- associated polypeptide or polynucleotide, reaction tubes, and instructions for testing metastatic breast cancer or metastatic lung cancer-associated activity. Optionally, the kit contains biologically active metastatic breast cancer or metastatic lung cancer protem. A wide variety of kits and components can be prepared according to the present invention, depending upon the intended user of the kit and the particular needs of the user. Diagnosis would typically involve evaluation of a plurality of genes or products. The genes will be selected based on conelations with important parameters in disease which may be identified in historical or outcome data.
Table 1 A shows about 461 genes pregulated In breast metastases to the brain relative to normal breast tissues These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 2A shows about 445 genes Upregulated in breast metastases to the brain relative to normal body tissues These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 3A shows about 216 genes upregulated In breast metastases to the brain relative to pπmary breast tumors These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 4A shows about 350 genes downregulated In breast metastases to the brain relative to pnmary breast tumors These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 5A shows about 489 genes downregulated In breast metastases to the brain relative to normal breast tissue These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 6A shows about 1251 genes upregulated in lung metastases to the brain relative to normal lung tissues These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 7A shows about 381 genes upregulated In lung metastases to the brain relative to normal body tissues These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 8A shows about 330 genes upregulated In lung metastases to the brain relative to pπmary lung tumors These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 9A shows about 252 genes downregulated In lung metastases to the brain relative to pnmary lung tumors These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 10A shows about 289 genes downregulated in lung metastases to the brain relative to normal lung tissue These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 11 A shows about 1198 genes upregulated in breast and lung metastases to the brain relative to normal body tissues These genes were selected from 59680 probesets on the Eos/Affymetnx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Table 12A shows about 2867 genes upregulated In breast and lung metastases to the brain relative to normal breast and lung tissues These genes were selected from 59680 probesets on the Eos/Affymetπx Hu03 Genechip array Gene expression data for each probeset obtained from this analysis was expressed as average Intensity (Al), a normalized value reflecting the relative level of mRNA expression
Tables 1B-12C shows the accession numbers for those pkeys in Tables 1A-12A lacking unlgenelD's For each probeset we have listed the gene cluster number from which the oligonucleotides were designed Gene clusters were compiled using sequences denved from Geπbank ESTs and mRNAs These sequences were clustered based on sequence simllanty using Clusteπng and Alignment Tools (DoubleTwist, Oakland California) The Genbank accession numbers for sequences compnsing each cluster are listed in the Accession column
Tables 1C-12C shows genomic positioning for those pkeys lacking unlgene ID's and accession numbers in tables 1A-12A For each predicted exon, we have listed the genomic sequence source used for prediction Nucleotide locations of each predicted exon are also listed
TABLE 1A About 461 genes unregulated In breast metastases to the brain relative to normal breast tissues
Pkey Unique Eos probeset Identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentile of breast metastases to the brain Als divided by the 90th percentlle of normal breast tissue Als, where the 15th percentile of all normal body tissue Als was subtracted from the both numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
419741 NM 007019 Hs 93002 ublquitln earner protein E2-C 23 16 3097 420542 NMJ00505 Hs 321 coagulation factor XII (Hageman factor) 1865 3398 407014 U38268 gb Human cytochrome b pseudogene, partia 1768 5 405452 Target Exon 1640 417900 BE250127 Hs 82906 CDC20 (cell division cycle 20, S cerevl 1423 26 419078 M93119 Hs 89584 Insulinoma associated 1 1405 2996 421693 X71490 Hs 106876 ATPase, H transporting, lysosomal (vacuo 1345 3499 422765 AW409701 Hs 1578 baculoviral IAP repeat-containing 5 (sur 12 17 38 408908 BE296227 Hs 250822 seriπe/threonlne kinase 15 11 78 12 410407 X66839 Hs 63287 carbonic anhydrase IX 11 66 1590 418836 AI655499 Hs 161712 BMP R1B 11 53 419875 AA853410 Hs 93557 proenkephalin 1059 412513 AA322599 Hs 5163 ESTs, Weakly similar to AF1518401 CGI 8 1050 400205 NMJ06265* Homo sapiens RAD21 (S pombe) 1040 443426 AF098158 HS 9329 chromosome 20 open reading frame 1 1028 426842 NM 004210 Hs 172700 neurallzed (Drosophila) like 1007
414358 AA476456 Hs 142614 ESTs 1005
427324 AA159587 Hs 285932 hypothetical protein FLJ23322 990
431070 AW408164 Hs 249184 transcnptlon factor 19 (SC1) 968
425397 J04088 Hs 156346 topoisomerase (DNA) II alpha (170kD) 953
430375 AW371048 Hs 93758 H4 hlstone family, member H 936
417308 H60720 Hs 81892 KIAA0101 gene product 935
429503 AA394183 Hs 204166 ESTs 935
432178 BE265369 Hs 272814 hypothetical protein DKFZp434E1723 933
444371 BE540274 Hs 239 forkhead box M1 914
407777 AA161071 Hs 71465 squaleneepoxldase 909
414907 X90725 Hs 77597 polo (Drosophia)-like kinase 873
430294 AI538226 Hs 32976 guanine nucleotide binding protein 4 852
400914 ENSP00000228091* Calcium binding protein 850
423198 M81933 Hs 1634 cell division cycle 25A 849
434916 AF161383 Hs 284207 Homo sapiens, Similar to RIKEN cDNA 1110 830
447342 AI199268 Hs 19322 Homo sapiens, Similar to RIKEN cDNA 2010 812
400292 AA250737 Hs 72472 BMP-R1B (bone morphogenetlc protein rec 807
419390 AI701162 Hs 90207 hypothetical protein MGC11138 798
403532 NMJ24638 Homo sapiens hypothetical prot 797
402542 Target Exon 797
422799 AI933199 Hs 120911 neurexophllin 4 795
421506 BE302796 Hs 105097 thymldine kinase 1, soluble 779
436877 AA931484 Hs 121255 ESTs, Weakly similar to T21069 hypotheti 773
414432 BE378174 Hs 26506 Homo sapiens clone CDABP0005 mRNA sequen 756
406690 M29540 Hs 220529 carciπoembryonlc antigen related cell ad 756
428865 BE544095 Hs 164960 BarH-Iike homeobox 1 7 54
437929 T09353 Hs 106642 ESTs, Weakly similar to T09052 hypotheti 750
411006 AW813193 Hs 17767 KIAA1554 protein 743
453439 AI572438 Hs 32976 guanine nucleotide binding protein 4 740
451930 BE259124 Hs 27262 Homo sapiens clone 25110 mRNA sequence 740
448409 AW069807 Hs 134726 ESTs, Moderately similar to PC4259 fern 737
412140 AA219691 Hs 73625 RAB6 interacting, klnesiπ-like (rabkmes 736
433272 AB043585 Hs 100890 candidate mediator of the p53 dependent 734
457465 AW301344 Hs 122908 DNA replication factor 733
422961 Y13620 Hs 122607 B cell CLUIymphoma 9 729
436876 AI124756 Hs 5337 Isocltrate dehydrogenase 2 (NADP), mltoc 726
401451 NM_004496* Homo sapiens hepatocyte nude 724
457211 AW972565 Hs 32399 ESTs, Weakly similarto S51797 vasodilat 7 16
429353 AL117406 Hs 335891 ATP-biπding cassette transporter MRP8 7 14
451346 NM 006338 Hs 26312 glioma amplified on chromosome 1 protein 7 12
428648 AF052728 Hs 188021 potassium voltage-gated channel, subfaml 7 10
453028 AB006532 Hs 31442 RecQ protein like 4 707
423551 AA327598 Hs 89633 ESTs 707
453968 AA847843 Hs 62711 High mobility group (nonhistonechromoso 700
421487 AFO27406 Hs 104865 serine/threonlne kinase 23 698
425371 D49441 Hs 155981 mesotheliπ 696
443347 AI052543 Hs 133244 melanoma denved leucme zipper, extra n 695
421458 NM_003654 Hs 104576 carbohydrate (keratan sulfate Gal 6) sul 684
402265 Target Exon 682
432180 Y18418 Hs 272822 RuvB (E coll homolog) like 1 670
403291 Target Exon 667
412856 BE386745 Hs 74631 baslgin (OK blood group) 6 66
453392 U23752 Hs 32964 SRY (sex determining region Y) box 11 665
401076 C11000393 gl|7305361|ref|NP_038652 1| ot 665
428484 AF104032 Hs 184601 solute carrier family 7 (cationic ammo 664
422296 AA360231 Hs 114416 Homo sapiens, Similar to transducln (bet 664
427914 AA417350 Hs 20575 ESTs 659
436291 BE568452 Hs 344037 protein regulator of cytokinesis 1 657
414064 BE245289 Hs 16165 expressed In activated T/LAK lymphocytes 656
402907 NMJJ24777* Homo sapiens hypothetical pro 655
458814 AI498957 Hs 170861 ESTs, Weakly similar to Z195_HUMAN ZINC 655
426686 AI362802 Hs 171814 parathymosln 652
402078 Target Exon 647
407168 R45175 Hs 117183 ESTs 646
426553 AA381293 Hs 23598 ESTs 645
403988 C5001831 gl|11O56O14|ref|NP_067651 1| ac 640
452969 92792 Hs 77575 hypothetical protein MGC3136 637
402961 Homo sapiens mRNA, cDNA DKFZp761E0611 (f 633
422938 NM-.001809 Hs 1594 centromere protein A (17kD) 632
402217 C19001662* gl|6753872|ref|NP_034345 1| I 632
432221 M21191 Hs 273415 aldolase A, fructose-blsphosphate 630
443723 Al 144442 Hs 157144 syntaxln 6 6 27
419081 AI798863 Hs 87191 ESTs 627
402649 Target Exon 620
400183 Eos Control 620
415262 H95572 Hs 206521 YME1 (S cerevlslaβ) like 1 609
421582 AI910275 trefoil factor 1 (breast cancer, estroge 608
405046 C3000978 gl|9280045Idbj|BAB01579 1| (ABO 608
409015 BE389387 Hs 49767 NMJ04553 Homo sapiens NADH dehydrogenas 606
424047 AI868401 Hs 138248 hypothetical protein YH95C04 605
420005 AW271106 Hs 133294 ESTs 603
403026 Target Exon 603
430532 D61216 Hs 18672 ESTs 602
430167 Y08976 Hs 234759 FEV protein 602
421242 AW161386 Hs 13561 hypothetical protein MGC4692 601 427239 BE270447 ublquitin carrier protein 599
447946 AI566164 Hs 277445 ESTs 597
449722 BE280074 Hs 23960 cyclin B1 595
423226 AA323414 Hs 146109 ESTs, Weakly similar to T28937 hypotheti 594
439963 AW247529 Hs 6793 platelet-activating factor acetylhydrola 592
445470 AI239871 Hs 154758 ESTs 591
403804 Target Exon 590
428450 NM 014791 Hs 184339 KIAA0175 gene product 589
406947 L10403 Hs 3134 DNA binding protein amplifying expressio 585
418951 F07809 Hs 89506 paired box gene 6 (aniπdla, keratitis) 585
406137 NMJ00179* Homo sapiens mutS (E coli) h 579
414416 AW409985 Hs 76084 hypothetical protein MGC2721 578
415539 AI733881 Hs 72472 BMP-R1B (bone morphogenetic protein rec 577
441761 AI222880 gb qp40c06 x1 NCI_CGAP_Co8 Homo sapiens 577
449644 AW960707 Hs 148324 ESTs 577
429901 AK000502 Hs 56237 hypothetical protein FLJ20495 575
418526 BE019020 Hs 85838 solute carrier family 16 (monocarboxyllc 575
421625 AA405386 Hs 178004 ESTs 574
405146 C8001690* gll6754446|ref|NPJ)34760 1| kl 566
424441 X14850 Hs 147097 H2A hlstone family, member X 565
443792 AI763073 Hs 204873 ESTs 563
457341 BE181716 gb QV1-HT0639-150500 198-e03 HT0639 Homo 562
403384 C4000351* gi|8394456|ref|NP_059138 1| to 562
408157 AA047685 Hs 62946 ESTs 560
405968 Target Exon 560
407701 AW375009 Hs 164407 ESTs 558
432917 NM 014125 Hs 241517 PRO0327 protein 557
422168 AA586894 Hs 112408 S100 calcium binding protein A7 (psonas 556
418322 AA284166 Hs 84113 cyclin-dependent kinase inhibitor 3 (CDK 555
433157 AW769671 ESTs, Moderately similar to CBX4_HUMAN C 555
400222 NM_002082* Homo sapiens G protein couple 554
419444 NM 002496 Hs 90443 Target CAT 554
421937 AI878857 Hs 109706 hematologlcal and neurological expressed 554
441153 BE562826 gb 601336534F1 NIH_MGC_44 Homo sapiens c 553
429671 BE379335 Hs 211594 proteasome (prosome, macropaln) 26S subu 5 53
407242 M18728 gb Human nonspecific crossreactlng antig 553
429469 M64590 Hs 27 glyclne dehydrogenase (decarboxylatiπg, 553
400340 AJ223798 homeo box 11 like 2 553
405467 Target Exon 550
426081 M69238 Hs 166172 aryl hydrocarbon receptor nuclear transl 549
404321 NA C7001741*gι|2499629lsp|Q63932|MPK2_MOUS 549
439573 AW137640 Hs 231444 Homo sapiens, Similar to hypothetical pr 548
437433 R74016 Hs 121581 ESTs 547
440475 AI807671 Hs 24040 potassium channel, subfamily K, member 3 546
438552 AJ245820 Hs 6314 type I transmembrane receptor (seizure r 542
403882 Target Exon 542
411734 AW374954 Hs 71779 Homo sapiens DNA from chromosome 19, cos 540
412377 AW947540 gb RC0 MT0002-140300 011-g10 MT0002 Homo 538
432562 BE531048 Hs 278422 DKFZP586G1122 protein 538
411358 R47479 Hs 94761 KIAA1691 protein 538
416361 AW204907 Hs 6872 ESTs, Weakly similar to CA13_HUMAN COI±A 537
418514 AW068487 Hs 25413 TOLLIP protein 537
443537 D13305 Hs 203 cholecystoklnln B receptor 535
445329 AW206378 Hs 144809 ESTs 535
452700 AI859390 Hs 288940 five-span transmembrane protein M83 534
438364 AK000860 Hs 6191 hypothetical protein DKFZp762H66 533
408901 AK001330 Hs 48855 hypothetical protein FU10468 533
447836 F11364 gb HSC2VH051 normalized infant brain cDN 529
442790 AW663221 Hs 159057 ESTs 527
408310 AW179023 Hs 191705 gb PM3-ST0036-170899 001-e08 ST0036 Homo 527
407792 AI077715 Hs 39384 putative secreted ligand homologous to f 526
413597 AW302885 Hs 117183 ESTs 526
430636 Z83737 Hs 247696 H3 hlstone family, member J 523
437673 AW665665 Hs 153034 ESTs 522
413278 BE563085 Hs 833 Interferon stimulated protein, 15 kDa 520
418004 U37519 Hs 87539 aldehyde dehydrogenase 3 family, member 519
402990 Target Exon 519
450278 AW205234 Hs 201587 ESTs 518
411678 AI907114 Hs 71465 squalene epoxldase 516
453160 AI263307 H2B hlstone family, member L 516
444734 NM 01360 Hs 11806 7-dehydrocholesterol reductase 515
429451 BE409861 Hs 202833 heme oxygenase (decycllng) 1 514
405501 Target Exon 514
427560 AA405394 Hs 161851 ESTs 513
428301 AW628666 Hs 98440 ESTs, Weakly similar to I38022 hypotheti 513
402586 ENSP00000241318* DJ947L8 1 1 (novel CUB 513
428566 U41763 Hs 184916 clathπn, heavy polypeptlde-llke 1 512
401612 C4000495gi|6677633|ref|NP 0335951|zln 511
404120 C5000537* gl|3298595|gb|AAC41376 1| (AF0 510
405850 Target Exon 510
433055 AF073727 Hs 279953 EH domain binding mltotic phosphoproteln 509
405210 ENSP00000244302* CDNA FLJ11591 fls, clon 507
455416 AW937143 gbPM1-DT0041-281299001 f01 DT0041 Homo 507
428182 BE386042 Hs 293317 ESTs, Weakly similar to GGC1JHUMAN G ANT 505
407239 AA076350 Hs 67846 leukocyte Immunoglobulin like receptor, 503
449162 A1632740 Hs 10476 ESTs 502 434203 BE262677 Hs 283558 hypothetical protein PR01855 502
434567 AK000600 Hs 3972 NeuAc-alpha-2,3 Gal beta-1,3 GalNAc-alph 502
433113 AA622130 Hs 152524 ESTs, Weakly simllarto PGCB MOUSE BREVI 500
432504 AL121015 Hs 277704 oxygen regulated protein (150kD) 499
431667 AA812573 Hs 246787 ESTs 499
428970 BE276891 Hs 194691 retinoic acid Induced 3 (RAIG1) metabo 499
416700 AW498958 Hs 343475 cathepsln D (lysosomal aspartyl protease 499
446230 AA134486 Hs 7155 ESTs, Moderately similar to 2115357ATYK 498
434637 AF147432 Hs 176926 ESTs 497
453857 AL080235 Hs 35861 Ras induced senescence 1 (RIS1) 497
429438 AC006293 Homo sapiens killer cell Ig-like recepto 495
414222 AL135173 Hs 878 sorbitol dehydrogenase 495
423541 AA296922 Hs 129778 serine protease Inhibitor, Kazal type 4 494
422095 AI868872 Hs 282804 hypothetical protein FLJ22704 493
453885 AW002629 Hs 259220 ESTs 493
426006 R49031 Hs 22627 ESTs 491
405979 Target Exon 491
433352 AA376773 gb EST89237 Small intestine I Homo sapie 490
453922 AF053306 Hs 36708 budding uninhibited by benzimldazoles 1 490
447388 AW630534 Hs 76277 Homo sapiens, clone MGC 9381, mRNA, comp 488
412988 BE046680 gb hn42h03 x1 NCI CGAP RDF2 Homo sapiens 488
409310 R88721 Hs 164584 ESTs 488
436481 AA379597 HS 5199 HSPC150 protein simllarto ublqultln con 487
406685 M18728 gb Human nonspecific crossreacting antig 487
429294 AA095971 Hs 198793 Homo sapiens cDNA FLJ22463 fis, clone H 486
418675 AW299723 Hs 87223 bone morphogenetic protein receptor, typ 486
427715 BE245274 Hs 180428 KIAA1181 protein 486
425443 AW157547 Hs 115329 ESTs 485
402885 Target Exon 4 84
407704 BE315072 Hs 78768 malignant cell expression enhanced gene/ 484
437352 AL353957 Hs 284181 hypothetical protein DKFZp434P0531 483
404790 C12001707*gi|7305215|ref|NP_038599 1| k 482
427747 AW411425 Hs 180655 serine/threoπine kinase 12 480
450149 AW969781 Hs 132863 Zic family member 2 (odd paired Drosophl 480
412519 AA196241 Hs 73980 tropontn T1, skeletal slow 479
401281 DKFZP586N2124 protein 478
432969 AA780472 Hs 335557 ESTs 478
445075 AI651827 ESTs 478
406981 S71129 acetylcholiπesterase (YT blood group) 478
409162 H25530 Hs 50868 solute earner family 22 (organic cation 477
428405 Y00762 Hs 2266 chollnerglc receptor, nicotinic alpha p 477
452838 U65011 Hs 30743 preferentially expressed antigen In mela 476
453005 AW055308 Hs 31803 ESTs, Weakly similar to N WASP [H saplen 476
418203 X54942 Hs 83758 CDC28 protein kinase 2 475
453712 AW403791 Hs 55067 hypothetical protein MGC15437 475
406718 AA505525 Hs 169476 glyceraldehyde-3 phosphate dehydrogenase 474
411598 BE336654 Hs 70937 H3 histoπe family, member A 473
431882 NM 001426 Hs 271977 engrailed homolog 1 473
443219 AI354669 Hs 187461 ESTs, Weakly simllarto C29149 praline r 473
438956 W00847 Hs 135056 Human DNA sequence from clone RP5 850E9 473
418960 NM 004494 Hs 89525 hepatoma-deπved growth factor (HDGF) 472
457739 AF161337 Hs 283928 Homo sapiens HSPC074 mRNA partial eds 471
412999 BE046255 gb hn38g10 x2 NCI_CGAP_RDF2 Homo sapiens 470
420856 BE513294 Hs 205736 HLA class II region expressed gene KE2 469
408633 AW963372 Hs 46677 PRO2000 protein 469
435602 AF217515 Hs 283532 uncharacteπzed bone marrow protein BM03 469
435493 AW135312 Hs 117237 ESTs 468
409469 AW517236 Hs 318393 ESTs 468
407137 T97307 gb ye53h05 s1 Soares fetal liver spleen 467
444441 AW613841 Hs 301394 hypothetical protein MGC3101 467
410959 AW811873 gb RC2 ST0168 071299-013 h10 ST0168Homo 467
402504 C1003823* gl|4826521|emblCAB42853 1| (AL 467
417037 BE083936 Hs 80976 antigen identified by monoclonal antibod 466
433399 N46406 Hs 84700 similar to phosphatidylcholine transfer 465
436057 AJ004832 Hs 5038 neuropathy target esterase 465
409034 AI684149 Hs 172035 hypothetical protein similar to mouse HN 465
422830 AC007954 Hs 121371 hypothetical protein DKFZp434P0111 464
421975 AW961017 Hs 6459 hypothetical protein FLJ11856 464
419760 AA668227 Hs 316625 gb ab77e07 s1 Stratageπe fetal retina 93 463
400657 Target Exon 463
425003 AF119046 Hs 154149 apurinlc/apyrim!dinlceπdonuclease(APEX 461
432241 AI937060 Hs 6298 KIAA1151 protein 461
459010 AA331438 gb EST35269 Embryo, 8 week I Homo sapien 461
438577 AA811184 Hs 259785 carnitine palmitoyltransferase I, liver 461
441593 AA939228 Hs 163412 ESTs 461
440238 AW451970 Hs 155644 paired box gene 2 461
429883 AI125209 Hs 123848 ESTs 459
428500 AI815395 Hs 184641 fatty acid desaturase 2 459
450029 AW073380 Hs 267963 hypothetical protein FLJ10535 458
436608 AA628980 Hs 192371 down syndrome critical region protein DS 458
411263 BE297802 Hs 69360 kinesln like 6 (mltotlc centromere-assoc 4 58
403156 C2001591 gl|10566471|dbJ|BAB15806 1| (AB 458
437026 AW976573 ESTs 457
403481 Target Exon 457
432886 BE159028 Hs 279704 chromatin accessibility complex 1 456
450935 BE514743 tumor suppressor deleted In oral cancer- 455 454425 AW300927 Hs 27192 hypothetical protein dJ1057B202 455
423306 W88562 Hs 108198 ESTs 455
442505 AW003775 Hs 343822 UDP-Gal betaGlcNAc beta 1 ,4- galactosylt 454
429345 R11141 Hs 199695 hypothetical protein 453
407300 AA102616 Hs 120769 gb zn43e07 s1 Stratagene HeLa cell s393 453
405333 Target Exon 453
402808 ENSP00000235229 SEMB 453
429746 AJ237672 Hs 214142 5,10-methylenetetrahydrofolate reductase 453
448604 AI546830 gb PN21_07_D12 r mynorm Homo sapiens cD 452
410156 AA082005 Hs 9634 ESTs 452
418216 AA662240 Hs 283099 AF15q14 protein 451
459358 T24769 Hs 343627 hypothetical protein FLJ12998 450
426516 BE262660 Hs 170197 glutamlc oxaloacetlctransaminase 2, mlt 450
440061 BE396581 gb 601288812F1 NIH_MGC_8 Homo sapiens cD 450
422997 BE018212 Hs 122908 DNA replication factor 450
407376 AA993138 Hs 142287 ESTs, Weakly simllarto ALUF_HUMAN llll 449
408877 AA479033 Hs 130315 ESTs, Weakly simllarto A47582 B-cell gr 448
449256 AA059050 Hs 59847 ESTs 447
428227 AA321649 Hs 2248 small Inducible cytokine subfamily B (Cy 446
439273 AW139099 Hs 269701 ESTs 446
418758 AW959311 Hs 172012 hypothetical protein DKFZp434J037 446
417158 AW965223 Hs 110062 complement-c1q tumor necrosis factor rel 445
404157 C6001170 gl|6468391lemb|CAB61578 1| (AL0 445
421777 BE562088 Hs 108196 HSPC037 protein 445
416555 H63394 Hs 334792 ESTs 444
454422 AW072328 Hs 59728 Homo sapiens mRNA, cDNA DKFZp566C0546 (f 444
442432 BE093589 Hs 38178 hypothetical protein FLJ23468 444
444118 AA458542 Hs 10326 coatomer protein complex, subunlt epsllo 444
407561 BE313226 Hs 94761 KIAA1691 protein 444
405101 ENSP00000249234* Zinc finger protein 92 443
459709 AA653774 Hs 212084 ESTs 443
452833 BE559681 Hs 30736 KIAA0124 protein 443
440087 W28969 Hs 7718 hypothetical protein FLJ22678 443
453833 AF090320 Hs 35718 cytochrome P450, subfamily VIIIB (sterol 443
433145 BE256247 HS 7740 oxysterol binding protein like 1 443
408771 AW732573 Hs 47584 potassium voltage-gated channel, delayed 442
430820 AF194815 immunoglobulin lambda vaπable 4 3 442
458756 AW057910 Hs 282185 ESTs 442
432415 T16971 Hs 289014 ESTs, Weakly similar to A43932 mucin 2 p 441
433001 AF217513 Hs 279905 clone HQ0310 PRO0310p1 440
426691 NM 006201 Hs 171834 PCTAIRE protein kinase 1 440
435579 AI332373 Hs 156924 ESTs 440
402299 Target Exon 440
439926 AW014875 Hs 137007 ESTs 440
413762 AW411479 Hs 848 FK506 binding protein 4 (59kD) 439
406181 Target Exon 439
458098 BE550224 metallothloneln 1E (functional) 438
405573 Target Exon 437
434761 AW298777 Hs 192155 ESTs 437
424411 NM 005209 Hs 146549 crystallln betaA2 436
451827 BE387187 Hs 27184 growth factor, ervl (S cerevlsiae) like 436
445013 AF151022 Hs 300224 hypothetical protein 436
446439 D87437 Hs 15087 KIAA0250 gene product 435
456604 AW383770 Hs 131878 ESTs Highly similar to S22745 seππe/th 435
414423 BE045599 Hs 202612 ESTs 435
439602 W79114 Hs 58558 ESTs 435
427584 BE410293 Hs 179718 v-myb avlaπ myeloblastosls viral oncogen 435
400530 Target Exon 435
420352 BE258835 Hs 347540 gb 601117374F1 NIH_MGC_16 Homo sapiens c 434
402229 mltochondrial nbosomal protein S2 433
409902 AI337658 Hs 156351 ESTs 433
452012 AA307703 Hs 279766 kinesm family member 4A 433
409557 BE182896 Hs 3686 ESTs 433
452092 BE245374 Hs 27842 hypothetical protein FLJ11210 432
456623 AI084125 Hs 108106 transcπptlon factor 432
430361 AI033965 Hs 239926 sterol C4 methyl oxldase-llke 431
437150 R51407 Hs 77910 3 hydroxy-3 mefhylglutaryl Coenzyme A sy 431
428619 AK002140 Hs 187378 hypothetical protein FLJ11278 431
426902 AI125334 Hs 97408 ESTs 430
421994 BE542166 ESTs Weakly simllarto I78885 seπne/th 430
407539 X91103 gb H sapiens mRNA for Hr44 protein 430
428977 AK001404 Hs 194698 oyclln B2 429
410348 AW182663 Hs 95469 ESTs 429
406355 C5000598 gl|2136258|plr||l59377 template 428
454033 AF107457 Hs 37035 homeo box HB9 428
444893 AW249312 Hs 12109 WD40 protein Claol 428
424796 AW298244 Hs 266195 ESTs 428
410009 AA079555 Hs 146092 ESTs 428
401807 C7001350 gl|6578126|gb|AAF17706 1|AF0496 428
403347 Target Exon 427
448296 BE622756 Hs 10949 Homo sapiens cDNA FLJ14162 fls, clone NT 426
426613 U96132 Hs 171280 hydroxyacyl Coenzyme A dehydrogenase, ty 426
447987 BE621544 Hs 157160 hypothetical protein MGC2616 426
406043 Target Exon 425
439453 BE264974 Hs 6566 thyroid hormone receptor interactor 13 425
417207 N92226 Hs 338218 ESTs 425 428971 BE278404 Hs 285813 hypothetical protein FLJ11807 425
404816 ENSP00000251989* DJ100N22 1 (NOVEL EGF-L 425
425662 BE173463 proliferation-associated 2G4, 38kD 425
419409 AW297831 Hs 143792 hypothetical protein MGC2656 424
458744 AW445183 ESTs 424
452461 N78223 Hs 108106 transcription factor 424
436241 AI051175 Hs 119594 ESTs 423
404068 Target Exon 423
441362 BE614410 Hs 23044 RAD51 (S cerevisiae) homolog (E coli Re 422
442916 H15560 Hs 131833 ESTs 422
418897 AW016578 Hs 128630 ESTs 422
410211 NM 014347 Hs 296365 zinc finger protein 422
426989 AI815206 ESTs 421
425184 BE278288 Hs 155048 Lutheran blood group (Auberger b antigen 420
409757 NM 001898 Hs 123114 cystatln SN 420
424991 AA775471 Hs 241467 ESTs 420
438792 AW291313 Hs 254955 ESTs 420
452369 AA766459 gb oa32f07 s1 NCI CGAP GCB1 Homo sapiens 420
429873 AW268693 Hs 105713 ESTs 420
454171 AW854832 gb QV2-CT0261-201099011 f05 CT0261 Homo 420
418317 R59783 gb yh07f05 Soares infant brain 1NIB H 419
414362 AI347934 Hs 75932 N ethylmalelmide sensitive factor attach 419
431851 AI146349 Hs 271614 CGI-112 protein 419
457485 AW081072 Hs 115960 KIAA0939 protein 418
446342 BE298665 Hs 14846 solute caiTierfamily 7 (cationic amino 418
421254 AK001724 Hs 102950 coat protein gamma cop 418
432738 AI559493 Hs 165904 ESTs 417
406216 Target Exon 417
459679 AA936176 Hs 303666 gb om06b10 s1 Soares_NFL_T_GBC_S1 Homo s 417
420996 AK001927 Hs 100895 hypothetical protein FLJ10462 417
434225 AA627706 ESTs 417
416920 AA176455 Hs 80475 polymerase (RNA) II (DNA directed) polyp 416
441378 AA931826 Hs 126846 ESTs 416
437848 AI906419 Hs 284380 gamma-glutamyltransferase 1 415
442041 AW161137 Hs 209569 ESTs 415
458176 A1961519 Hs 140309 Homo sapiens, clone IMAGE 3677194, mRNA, 415
428732 AA432266 ESTs 415
440205 T86950 Hs 105448 ESTs, Weakly similar to B34087 hypotheti 415
456341 AA229126 gb nc45e10 s1 NCI_ CGAP_Pr3 Homo sapiens 415
408946 AW854991 Hs 255565 ESTs 415
417923 R26632 Hs 106510 ESTs, Moderately similar to ALU2_HUMAN A 414
419092 J05581 Hs 89603 mucin l, transmembrane 4 13
415228 AF030111 Hs 78281 regulator of G-proteln signalling 12 413
453377 AI679149 Hs 167186 ESTs 413
443361 AI792628 Hs 133273 ESTs 413
425453 AW374284 Hs 237617 Homo sapiens chromosome 19, cosmld R2689 413
437933 A1276132 ESTs 412
448484 BE613340 Hs 334725 Homo sapiens, Similar to RIKEN cDNA 9430 411
431629 AU077025 Hs 265827 Interferon, alpha Inducible protein (do 411
416138 C18946 Hs 79026 myelold leukemia factor 2 411
417866 AW067903 Hs 82772 collagen, type XI, alpha 1 411
408349 BE546947 Hs 44276 homeo box C10 410
405945 Target Exon 410
431611 U58766 Hs 264428 tissue specific transplantation antigen 410
429485 AW197086 Hs 99338 ESTs 410
456847 AI360456 Hs 37776 ESTs 410
435043 AI276478 ESTs 410
413976 BE295452 Hs 75655 procollagen prollne, 2 oxoglutarate 4 di 409
431374 BE258532 Hs 251871 CTP synthase 409
419102 AA234098 Hs 42424 ESTs, Weakly simllarto 2004399A chromos 409
453863 X02544 Hs 572 orosomucold 1 409
404755 Target Exon 408
448633 AA311426 Hs 21635 tubulin, gamma 1 408
418478 U38945 Hs 1174 cyclin-dependent kinase Inhibitor 2A (me 408
425966 NM 001761 Hs 1973 cyclin F 408
409929 R38772 Hs 172619 myelin transcription factor 1-llke 408
440042 AI073387 Hs 133898 ESTs 408
437679 NM 014214 Hs 5753 lnositol(myo)-1(or4) monophosphatase 2 407
447995 AI742618 Hs 181733 ESTs, Weakly simllarto nitπlase homolo 407
417059 AL037672 Hs 81071 extracellular matrix protein 1 407
427719 AI393122 Hs 134726 ESTs 407
431912 AI660552 ESTs, Weakly similar to A56154 Abl subst 407
411377 AW841462 gb RC6 CN0014-080300-012-B09 CN0014 Homo 407
418205 L21715 Hs 83760 troponin I, skeletal, fast 406
444806 AI197853 Hs 312841 ESTs 405
455513 AW983772 gb RC3 HN0002-060400 012-h09 HN0002 Homo 405
407487 S70348 gb Homo sapiens integrin beta 3 mRNA, pa 405
451365 AI791783 Hs 16063 ESTs, Weakly simllarto ALU8_HUMAN ALU S 405
420848 NM 005188 Hs 99980 Cas-Br-M (muπne) ecotroplc retroviral t 405
442739 NM 007274 Hs 8679 cytosollc acyl coenzyme A thloester hydr 405
445871 AI7O2901 Hs 145582 ESTs, Weakly simllarto FOR4 MOUSE FORMI 405
412007 AA999846 Hs 71986 ESTs 405
459682 AW241940 Hs 102500 hypothetical protein FLJ20481 404
425234 AW152225 Hs 165909 ESTs, Weakly similar to I38022 hypotheti 404
410082 AA081594 Hs 158311 Musashl (Drosophila) homolog 1 404
409776 AW499663 gb UI-HF-BROp-aJj d 03-0-UI rl NIH_MGC_5 404 452533 AW967801 Hs.151293 ESTs, Weakly similar to T42705 hypotheti 4.04
407673 AW064404 Hs.279825 ESTs 4.03
426609 AL040604 Hs.99344 hypothetical protein PRTD-NY3 4.03
422010 AA302049 Hs.31181 Homo sapiens cDNA: FLJ23230 fis, clone C 4.02
453435 AJ278473 Hs.297814 gb:AJ278473 Homo sapiens adult T-cell Ie 4.02
409844 AW502336 gb:UI-HF-BROp-aka-b-05-0-Ul.r1 NIH MGC_5 4.02
433294 AA582082 Hs.199410 ESTs 4.02
420415 L44281 Hs.73149 paired box gene 8 4.02
406253 Target Exon 4.02
414602 AW630088 Hs.76550 Homo sapiens mRNA; cDNA DKFZp564B1264 (f 4.01
425081 X74794 Hs.154443 mlnlchromosome maintenance deficient (S. 4.01
452613 AA461599 Hs.23459 ESTs 4.01
454831 AW833768 gb:QV4-TT0008-13O10O-077-e06 TT0008 Homo 4.00
443147 AI034351 Hs.19030 ESTs 4.00
414571 BE410746 Hs.22868 protein tyrosine phosphatase, non-recept 4.00
447316 AI373534 Hs.337577 ESTs 4.00
TARI F 1R
Pkey: Unique Eos probeset Identifier number
CAT number Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accession 400205 2538J NMJ06265 D38551 X98294 BM477931 BM461566 AU123557 AU133303 AU134649 AW500421 BM172439 AW500587 AW503665
AW504355 AW503640 BM152454 AW505260 AI815984 AW504075 AW500716 AL597310 BC001229 BM474371 AA984202 AU135205
BE090841 AW163750 BF747730 BF898637 AI206506 AV660870 AV692110 AW386830 AV656831 N84710 AW993470 BF086802
BF758454 BG960772 BF757769 BI870853 BE018627 C75436 AW148744 BF757753 BG622067 BE909924 AA708208 BG530266 BF968015
AW992930 BF888862 BG536628 AA143164 AW748953 BG498922 BF885190 BF889005 BF754781 BF800003 BM476529 AI627668
AW028126 AL046011 BF590668 A1017447 AA579936 AI367597 AA699622 BE280597 AI124620 AI082548 AW274985 AA677870 AI056767
BE551689 AA287642 H94499 AI752427 AI652365 AW002374 AW062651 AA360834 N68822 AU135442 AU125960 Z78334 BE545813
A1092115 BF312771 BF242859 BG533616 BG533761 BG164745 BG492433 BM473183 AA172043 AA172069 AU157092 AU151353
AU155318 BE302211 AI375022AA085641 AU157923 H88858 AA132730AA115113 AA909781 AI475256 AA424206AW572383AW084296
AI184820 AI469178 AA782432 H92184 AA340562 BF195818 AA852821 AW576342 AA827107 AA173317 AW190014 AI918514 AA729372
AA729718 AI055958 AA331424 BE328601 AA515690 BI018896 AW628277 AA748368 AA626222 BG492636 AW380620 BF800058
AW370956 AA290909 R25857 BG952995 BF801437 AA172077 AU155890 AU149783 AI720904 AA902936 AA865727 AI470830 AV740677
AA142982 AA482485 AU145485 AW576399 AU156042 R63448 BF246427 BE928472 D25910 BF758439 BF968785 BE565238 AA355981
A1905607 BG291148 BG533096 BG532888 BF030886 BG613756 BE928471 BG574501 AA187596 AA361196 T95557 BG531446
BG527242 BG527513 BG611106 AA085995 BF847252 BG024608 BE540261 BG531236 AL579993 BG108733 BG483503 BG571032
BG492505
400183 48154J X80199 NM 007359 BI553784 BG720095 BG899766 AI088926 BE857470 AI199713 AI870291 AL121179 AL577898 AA009896 AA868181
AA482924 AI637524 AW043834 AU156777 T30547 R05481 BE902481 AW372677 W73547 H51965 BF944628 BE825156 AL567238
AW372714 BF759809 AL578496 BE396176 H02384 BE007647 BF917244
421582 13358 X00474 NMJ03225 X52003 M12075 BI765761 AW950155 AI571948 BI760569 AA308400 AA568312 BI761955 AA507595 AA614579
AA614409 BF747698 BM142326 AA307578 AI925552 AA578674 AA582084 AW009769 AA514776 AA588034 BG271505 AA858276
BM142503 AW050700 AI307407 AI202532 AA524242 AI909772 AI970839 BG236516 AW750216 AA587613 AI909749 A1909751 AI910083
AA614539 R55292AA507418
427239 20459_2 AL532360 BE794750 AA582906 AI015067 AW271034 BG271636 AW075177 AW071374 AI345565 AI307208 BE138953 BE049086
AI334881 AW075006 AW075181 AA464019 AW302733 AW075100 AW073433 AI802854 AI334909 AI802853 AI345036 AI348921 AI340734
AI307478 AI251289 AW302327 AW072520 AI312145 AW073656 AW072513 AW071289 AI307559 AA876186 T29587 AI307493 AI255068
AI252868 AI252839 AW074809 AI252926 AI252160 AI251662 AI251262 AI610913 AI270787 AI270156 AI252075 AW073469 AW072901
AW072496 AW071420 AI305762 AI254764 AI802837 AI251264 AW073049 AW071311 AI340643 BE138965 BE138502 AW073456
AI334733 AI054335 BE139260 AI054302 AI054060 AI054057 AI053722 AI289711 BE139228 AW470478 AW271039 AW302085 BE041872
AI254494 AI271496 AI252427 BF718773 BF718645 AW074866 BE857822
441761 173757 1 BF796007 AI718138 BI600878 AI222880 AI719648 AI242524 AI242392 AA961560 BF770656 AW275807
457341 703 15 AW948320 BE181716 AW983981 AA484444 AW948314
433157 38399 2 AA578671 AI559353 AW769671 AW769665
400222 9287 3 NM 002082 L16862 BG828886 BE795217 BE904064 BE294526 BE297283 BE394617 BE935127 BE935106 F12351 BG823182 H16710
441153 264480 3 BE562826 BE378727
412377 1174171 1 AW947536 AW947523 AW947539 AW947540 AW947541 AW947535
447836 570540 1 BI086295 F11364 BE620332 AW877701 AW877654 AW877608 AW877766 T08447 BE887463 AW956871
453160 6028 5 BC009612 NMJ03526 BI597616 AV761592 AV760377 AL601008 BI604131 BE645918 BG187760 BG181525 BG210634 BG192999
AI263307 AA344186 AW952966 AAO33609 AA037562 AA722183 R79452 H70775 BF674991 BE769437 BG007856 AA037483 AW572535
AI143991 AA084581 AA033610 AV742510 AV735788 R08336
455416 1164250 AW937150 AW937151 AW937141 AW937174 AW937132 AW937173 AW937170 AW937165 AW937195 AW937145 AW937164 AW937137
AW937160 AW937142 AW937171 AW937191 AW937139 AW937143 AW937159 AW937140 AW937163 AW937135 AW937179 AW937156
429438 30460 1 NA
433352 61720 1 AF024708 AF024696 AA376773 BE927220 BG249309 BF741901 BF927642 BE176914 BF364317
412988 1342150 1 BE046680 BE046738 BE044958
406685 0 0 M18728
445075 2823108 1 AI651827AI206885AI699543
412999 1343220 1 BE046255 BE046611 BE046716 BE046732 BE046273
410959 1065309 1 AW811937AW811939 AW811934AW811873AW811951 AW811938 AW852485 AW811932 BE144621
459010 84453 1 AW955786 BF870627 AA251104 AA331438 AA016068 Z19751
437026 1240260 1 AW976573 AA742335 AA830000
450935 4469 1 BE349913 BC002850 BC016704 NM 005851 AF089814 AK001498 AL537879 BG754157 AI129659 AI261895 BG397540 BF663515
AW517226 BG677982 AI435188 AI453123 AI198380 AA524481 BG981512 AW269638 AI348113 AI095743 AA457108 AW044584
AU151602 AI744572 AI078741 AI879729 AI089613 AI568618 BF109806 AW440972 AA401965 AI027227 AI127506 AA434027 BF732901
AW264768 AA833667 AL038554 AI568161 AI350340 AA402084 BE677778 AA933621 BF663514 BG763563 AL574521 BG177226
BG759860 BE906329 AW161323 AI879350 BF946477 BF766208 AA633194 AL537880 AL038553 BG468205 BG761617 BI762655
BG436637 N49458 BI834722 BG397879 BI258799 AW004930 AA902847 AI832036 AW167549 AA743167 AA848017 AA365434 AI819503 AA767866 AI582000 N33615 AI950146 AA444029 AA227130 AA041525 AW339842 AA865972 AA838006 AW157822 AI890994 BI771150
BI821666 BE279491
448604 2997328 1 AI546830AI546838
440061 10031jT BG392038 AA090632 AL523849 R140O5 BE559751 430820 32425.1 AF194815AF194816 23945 1 AI082245 BE467534 AI797130 BE467063 BE467767 BE218421 AI694996 BE327781 BE327407 BE833829 AA989054 AA459718 BE833855
BE550224 AA832519 AF086393 AV733386 BE465409 N29245 W07677 AA482971 BE503548 H18151 AA461301 W79223 W74510
AI090689 AL600773 AL600781 N46003 R28075 R34182 BE071550 AW885857 AI276145 AI276696 H97808 N20540 AI468553
421994 I8-.1 BE542166 AI536692 W49486 AI554576 AI359949 AA329007 AA301695 AA887288 AW954743 BI053257 W49487 425662 29204_6 BF576185 BG392835 BF832725 AA348657 BE173463 H38593 AA361336 458744 827170.1 AW445183AI380746 426989 2898351 H10322 AW191920 AA581798 BF909366 BF909310 BF909357 BF909323 BF909317 BF909442 BF909364 BF909342 T23471 F02195
AA455133 F04743 D19749 AI224921 BF907691 BF909436 BF909433 BF909347 BF908960 BF911433 BF909439 BF909320 BF908633
BF909360 BF909344 BF909326 BF909330 BF909324 BF909322 AA394039 BF909349 AA857913 BF909352 BF912020 BF911220
BF909363 BF911329 BF909339 BF907711 BF909341 BF912530 BF912434 BF912513 BF912417 BF912223 BF909336 BF909328
BF911219 BF909356 BF909337 AI815206 BF912221 R49595 F02092 R44981 BF909318 BF380684 H17049 H05273 BF909312 BF909314
BF912225
452369 89607.1 AW968737 AA766459 AA025799
454171 10492401 AW854832 AW854798 AW854857 AW854816 AW854834 AW854817
4 41188331177 1 1117766992244.1 W22626 BF110459 BI020483 BI025592 BI020028 R59783 T24708
434225 18616921 AA627706 F28433 D63189
428732 139172 AW604761 BG496605 AL534435 N52169 Z40534 AL514785 BF834286 BF832372 AA102279 BG260063 AU123387 BG989683 BF887489
BG427243 AA757223 N46621 BE774691 BF223203 AI638487 AI685529 AI656376 AA628336 BF431278 N34895 AA705819 AI921735
AA432266 BE067482 AW601418 AI684438 AI251741 AI653304 AA595843 AA431254 AI419788 AI220525 AA620860 AA719177 AA860379
AW974279 Z47308 AA299472 AY072912 AL514786 Z44690 AA089566 F05145 AI557255 AI678039 AA926992 AY072910 BG718557
AU098965
456341 2456281 AA229126 AA229463
437933 7249221 AI276132 AA772500 AW295806 AI383186 BE698792 BE698799
435043 81113 AA662663 AI432402 AI276478 AI675712
431912 610.10 BI763666 BI517886 BI759051 AI688604 AI660552 BF588523 AW004785 AW295479 BF591117 BF002672 BF064073 AA594441 AI380340
AI700219 AI659950 AI688540 AW296326
411377 10794701 BE092475 BE156657 BE156668 AW841462
455513 12429451 AW983772 AW983837 AW983730 AW983769 AW983836 AW983835
407487 569981 S70348 BF593562 BG999385 BG999377
409776 9122131 AW499663 AW502643 AW502632
409844 9160851 AW502336 AW502339 AW501736 AW501839
454831 10736902 AW833435 AW833533 AW833768 AW833631 AW833557
TABLE 1C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (GI) numbers "Dunham I et al " refers to the publication enttled "The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495 Strand I ndicates DNA strand from which exons were predicted
NLpositlon Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLpositlon
405452 7656638 Minus 93876-94275
400914 3779013 Plus 116586-116729,117860-117986
403532 8076842 Minus 81750-81901
402542 9801558 Minus 67076-67594
401451 6634068 Minus 119926-121272
402265 3287673 Plus 21059-21168
403291 7230870 Plus 95177-95435
401076 3687273 Plus 8572585917
402907 6706902 Minus 8561-8692
402078 8117414 Minus 163935-164095,193229-193504
403988 8576087 Plus 16251-16462
402961 9453790 Plus 4296643193,53444-53524
402217 9795981 Minus 21521-21757
402649 9958202 Minus 69796-70414
405046 7596829 Minus 43734528
403026 7670575 Plus 56521-56840
403804 8139999 Minus 21048-21443
406137 9166422 Minus 30487-31058
405146 9438278 Minus 102529-102633
403384 9438321 Minus 178616-180277
405968 8247789 Plus 14893-15148
405467 7770659 Minus 17983-18674
404321 9665209 Minus 76594-77805
403882 7710258 Plus 60805-60997,62455-62559
402990 7631040 Minus 117579-118409
405501 9211311 Minus 4908549400,49565-49679,50117-50262
402586 9908948 Plus 11846-12041
401612 7705041 Minus 100597-100830
404120 7342152 Plus 135775-136000
405850 6164995 Plus 13871-14110
405210 7230142 Minus 81049-81327
405979 8247789 Minus 189378-190148
402885 9926751 Plus 71919-72049
404790 7230958 Plus 38611-38761
401281 9800073 Minus 13622-15130 402504 9797871 Plus 12366-12614
400657 7249004 Plus 160793-161343
403156 9838039 Minus 82105-82989
403481 9965004 Plus 93496-93633
405333 3165399 Plus 149905-150215
402808 6456148 Minus 114964-115136,115461-115585,115931-11604
404157 9886596 Minus 47629-49050
405101 8076859 Plus 130732-132266
402299 6693370 Plus 23367-25175
406181 5923650 Plus 16586-16855
405573 3820491 Minus 32645-33144
400530 6981826 Plus 39-541
402229 9965022 Minus 15739-15951,16166-16779
406355 9256052 Minus 97979-98656
401807 7331536 Plus 152325-152912
403347 8569747 Plus 654-1101
406043 6758938 Plus 36609-37156
404816 5911819 Minus 81825-81947,83523-83639,86204-86326
404068 3168621 Minus 18123-18766
406216 7382582 Plus 26949-27491
405945 6758796 Minus 24735-25158
404755 7706327 Minus 53729-53846
406253 7417725 Plus 62137-62741
TABLE 2A About 445 genes upregulated In breast metastases to the hraln relative to normal body tissues
Pkey Unique Eos probeset Identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentile of breast metastases to the brain Als divided by the 90th percentile of normal body tissue Als, where the 15th percentle of all normal body tissue Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ lD NO(s)
408591 AF015224 Hs 46452 mammaglobln 1 8490 11 88
429441 AJ224172 Hs 204096 llpophilln B (uteroglobln family member) 3341 54190
429170 NM 001394 Hs 2359 dual specificity phosphatase 4 3003 53108
407276 AI951118 Hs 326736 Homo sapiens breast cancer antgen NY BR 2635 8
400292 AA250737 Hs 72472 BMP R1B (bone morphogenetc protein rec 2060 2
419078 M93119 Hs 89584 insuliπoma associated 1 1898 2996
432441 AW292425 Hs 163484 Intron of hepatocyte nuclear factor-3 al 1725 59
408045 AW138959 Hs 245123 ESTs 1613 10
443171 BE281128 Hs 9030 TONDU 1465 68
400291 AA401369 downstream of breast cancer antigen NY-B 1250 1
404561 tπchorhinophalangeal syndrome I gene (T 1248
452838 U65011 Hs 30743 preferentially expressed antgen In mela 1245
432415 T16971 Hs 289014 ESTs, Weakly similar to A43932 mudn 2 p 1213
410102 AW248508 Hs 279727 ESTs, homologue of PEM-3 [Ciona savignyl 11 43
457465 AW301344 Hs 122908 DNA replication factor 1058
422656 AI870435 Hs 1569 LIM homeobox protein 2 10 13
425057 AA826434 Hs 1619 achaete-scute complex (Drosophila) homol 1008
400205 NM.006265* Homo sapiens RAD21 (S pombe) 985
407178 AA195651 AP-2 beta transcπption factor 923
450705 U90304 Hs 25351 Iroquois homeobox protein 2A (IRX-2A) ( 915
422756 AA441787 Hs 119689 glycoprotem hormones, alpha polypeptide 848
447342 AI199268 Hs 19322 Homo sapiens, Similar to RIKEN cDNA 2010 845
444783 AK001468 Hs 62180 anlllin (Drosophila Scraps homolog), act 825
401451 NM.004496* Homo sapiens hepatocyte nude 825
426283 NM 003937 Hs 169139 kyπurenmase (L-kynurenine hydrolase) 773
439926 AW014875 Hs 137007 ESTs 769
448275 BE514434 Hs 20830 kinesin like 2 768
422168 AA586894 Hs 112408 S100 calcium binding protein A7 (psoπas 766
416208 AW291168 Hs 41295 ESTs, Weakly simllarto MUC2.HUMAN MUCIN 765
457211 AW972565 Hs 32399 ESTs, Weakly similar to S51797 vasodilat 764
447475 AI380797 Hs 158992 ESTs 748
439979 AW600291 Hs 6823 hypothetical protein FLJ10430 747
411096 U80034 Hs 68583 mitochondria! intermediate peptidase 743
418836 AI655499 Hs 161712 BMP-R1B 739
458098 BE550224 metallothloneln 1E (functional) 723
409731 AA125985 Hs 56145 thymosin, beta, Identified in neuroblast 720
430287 AW182459 Hs 125759 ESTs, Weakly simllarto LEU5.HUMAN LEUKE 705
417576 AA339449 Hs 82285 phosphonbosylglyclnamlde formyltransfer 705
458814 AI498957 Hs 170861 ESTs, Weakly simllarto Z195.HUMAN ZINC 698
451807 W52854 hypothetical protein FLJ23293 simllarto 698
425048 H05468 Hs 164502 ESTs 695
428342 AI739168 Homo sapiens cDNA FLJ13458 (Is, clone PL 685
407300 AA102616 Hs 120769 gb zn43e07 s1 Stratagene HeLa cell s393 685
409557 BE182896 Hs 3686 ESTs 678
428227 AA321649 Hs 2248 small Inducible cytokine subfamily B (Cy 675
415786 AW419196 Hs 257924 hypothetical protein FLJ13782 670
408771 AW732573 Hs 47584 potassium voltage-gated channel, delayed 668
445413 AA151342 Hs 12677 CGI-147 protein 663
427365 AI873274 downstream of breast cancer antigen NY-B 662
408908 BE296227 Hs 250822 serine/threonlnβ kinase 15 658
407999 AI126271 Hs 49433 ESTs, Weakly simllarto YZ28.HUMAN HYPOT 647
415539 AI733881 Hs 72472 BMP-R1B (bone morphogenetlc protein rec 647
441377 BE218239 Hs 202656 ESTs 645
439963 AW247529 Hs 6793 platelet activating factor acetylhydrola 644
423242 AL039402 Hs 125783 DEME 6 protein 638
427528 AU077143 Hs 179565 minichromosome maintenance deficient (S 638
452786 R61362 Hs 106642 ESTs, Weakly simllarto T09052 hypotheti 635
453884 AA355925 Hs 36232 KIAA0186 gene product 633
413597 AW302885 Hs 117183 ESTs 623
418819 AA228776 Hs 191721 ESTs 614
411598 BE336654 Hs 70937 H3 hlstone family, member A 608
443715 AI583187 Hs 9700 cycliπ E1 605
416135 AW473656 Hs 227277 ESTs 603
433675 AW977653 Hs 75319 ribonucleotlde reductase M2 polypeptide 598
425234 AW152225 Hs 165909 ESTs, Weakly simllarto I38022 hypotheti 584
416933 BE561850 Hs 80506 small nuclear nbonucleoprotein polypept 583
407756 AA116021 Hs 38260 ublqultln specific protease 18 567
419875 AA853410 Hs 93557 proenkephalln 565
451398 AI793124 Hs 144479 ESTs 564
412140 AA219691 Hs 73625 RAB6 Interacting, kinesin like (rabkines 557
450149 AW969781 Hs 132863 Zlc family member 2 (odd-paired Drosophl 553 425843 BE313280 Hs 159627 death associated protein 3 551
422805 AA436989 Hs 121017 H2A hlstone family, member A 550
426451 AI908165 Hs 169946 GATA binding protein 3 (T cell receptor 525
401519 C15000476* giI12737279|reflXP_012163 1| 525
426878 BE069341 Homo sapiens breast cancer antgen NY-BR 520
407366 AF026942 Hs 17518 gb Homo sapiens clg33 mRNA, partial sequ 518
432378 AI493046 Hs 146133 ESTs 5 18
425707 AF115402 Hs 11713 E74 like factor 5 (ets domain transcript 5 15
433023 AW864793 thrombospondin 1 515
424399 AI905687 AI905687 IL-BT095-190199 019 BT095 Homo 514
409269 AA576953 Hs 22972 steroid 5 alpha reductase 2 like, H5AR g 513
448105 AW591433 Hs 298241 Transmembrane protease, seπne 3 508
453392 U23752 Hs 32964 SRY (sex determining region Y) box 11 505
425692 D90041 Hs 155956 N acetyltransferase 1 (arylamlπe N-acety 503
403485 C3001813* gι|12737279|rβf|XP_0121631) k 503
452461 N78223 Hs 108106 traπscπption factor 503
443537 D13305 Hs 203 cholecystokmln B receptor 500
432140 AK000404 Hs 272688 hypothetical protein FLJ20397 498
422486 BE514492 Hs 117487 gene nearHD on 4p163 with homology to 495
433043 W57554 Hs 125019 lymphold nuclear protein (LAF 4) mRNA 488
408035 NM 006242 Hs 42215 protein phosphatase 1, regulatory subuni 4 85
424735 U31875 Hs 272499 DHRS2 Dehydrogenase/reductase (SDRfamll 485
424905 NM 002497 Hs 153704 NIMA (neverin mitosis gene a) related k 485
444342 NM 014398 Hs 10887 simllarto lysosome associated membrane 483
419536 AA603305 gb np12d11 s1 NCI_CGAP_Pr3 Homo sapiens 480
409435 AI810721 Hs 95424 ESTs 478
401464 histone deacetylase 5 473
414343 AL036166 Hs 75914 coated vesicle membrane protein 473
453863 X02544 Hs 572 orosomucold 1 470
410467 AF102546 Hs 63931 dachshund (Drosophila) homolog 470
415989 AI267700 ESTs 470
449722 BE280074 Hs 23960 cyclin B1 469
418092 R45154 Hs 338439 ESTs 468
409542 AA503020 Hs 36563 hypothetical protein FLJ22418 467
444858 AI199738 Hs 208275 ESTs, Weakly simllarto ALUA.HUMAN llll 465
416111 AA033813 Hs 79018 chromatln assembly factor , -ubunιt A ( 465
450193 AI916071 Hs 15607 Homo sapiens Fanconl anemia complementat 461
409902 AI337658 Hs 156351 ESTs 453
422835 BE218705 Hs 121378 metallothloneln like 5 testis specific 450
433323 AA805132 Hs 159142 ESTs 450
448826 AI580252 Hs 293246 ESTs, Weakly simllarto putative p150 (H 448
401866 Target Exon 448
430044 AA464510 Hs 152812 ESTs 443
453439 Al 572438 Hs 32976 guanine nucleotide binding protein 4 438
453160 AI263307 H2B hlstone family, member L 438
432886 BE159028 Hs 279704 chromatn accessibility complex 1 436
414271 AK000275 Hs 75871 protein kinase C binding protein 1 435
436608 AA628980 Hs 192371 down syndrome cntcal region protein DS 434
427712 AI368024 Hs 283696 ESTs 434
424085 NM 02914 Hs 139226 replication factor C (activator 1) 2 (40 433
404571 NM.O15902* Homo sapiens progestin induce 433
429986 AF092047 Hs 227277 sine oculls homeobox (Drosophila) homolo 425
450325 AI935962 Hs 91973 ESTs 423
442861 AA243837 Hs 57787 ESTs 423
431585 BE242803 Hs 262823 hypothetical protein FLJ 10326 423
426501 AW043782 Hs 293616 ESTs 421
448664 AI879317 Hs 334691 splicing factor 3a subunlt l 120kD 420
443695 AW204099 ESTs, Weakly similar to AF1267801 retin 418
432201 AI538613 Hs 298241 Transmembrane protease, serine 3 416
407980 AA046309 Hs 344241 gb zf12f01 s1 Soares fetal heart_NbHH19W 415
433285 AW975944 Hs 237396 ESTs 414
447519 U46258 Hs 339665 ESTs 4 13
451752 AB032997 KIAA1171 protein 4 12
426581 AB040956 Hs 135890 KIAA1523 protein 410
436488 BE620909 Hs 261023 hypothetical protein FLJ20958 410
437389 AL359587 Hs 271586 hypothetical protein DKFZp762M115 408
418700 AI963808 Hs 86970 ESTs, Moderately similar to ALU5.HUMAN A 408
442760 BE075297 Hs 6614 ESTs, Weakly similar to A43932 mucln 2 p 408
427427 AF077345 Hs 177936 lectln, superfamlly member 1 (cartilage 407
437834 AA769294 gb nz36g03 s1 NCI.CGAP.GCB1 Homo sapiens 405
436291 BE568452 Hs 344037 protein regulator of cytokinesis 1 402
441362 BE614410 Hs 23044 RAD51 (S cerevisiae) homolog (E coll Re 401
400528 NM.020975* Homo sapiens ret proto-oncoge 401
414706 AW340125 Hs 76989 KIAA0097 gene product 401
446999 AA151520 hypothetical protein MGC4485 400
434203 BE262677 Hs 283558 hypothetical protein PR01855 399
414670 BE409525 Hs 902 neuroflbromln 2 (bilateral acoustic neur 398
419743 AW408762 Hs 5957 Homo sapiens clone 24416 mRNA sequence 397
438321 AA576635 Hs 6153 CGI-48 protein 397
448686 AA158659 Hs 334712 hypothetical protein FLJ 14744 395
415263 AA948033 Hs 130853 ESTs 393
423175 W27595 Hs 347310 hypothetical protein FLJ 14627 393
433409 AI278802 Hs 25661 ESTs 390
418113 AI272141 Hs 83484 SRY (sex determining region Y) box 4 388
427811 M81057 Hs 180884 carboxypeptdase B1 (tissue) 386
447334 AA515032 Hs 91109 ESTs 386 415621 AI648602 Hs.55468 ESTs 3.85
432840 AK001403 Hs.279521 hypothetical protein FLJ20530 3.84
436167 AA705651 Hs.25087 ESTs 3.83
421037 AI684808 Hs.197653 ESTs 3.83
423165 AI937547 Hs.124915 hypothetical protein MGC2601 3.81
443347 AI052543 Hs.133244 melanoma-derived leuclne zipper, extra-n 3.81
424800 AL035588 Hs.153203 MyoD family Inhibitor 3.81
425529 NM 014656 Hs.158282 KIAA0040 gene product 3.77
409648 AW451449 Hs.57749 ESTs 3.75
426827 AW067805 Hs.172665 methylenetetrahydrofolate dehydrogenase 3.75
420650 AA455706 Hs.44581 heat shock protein hsp70-related protein 3.74
434569 AI311295 Hs.344478 KIAA0196 gene product 3.73
428654 NM 012091 Hs.188661 adenoslne deamlnase, tRNA-spec'flc 1 3.70
407378 AA299264 Hs.57776 ESTs, Moderately similar to I38022 hypot 3.70
404632 NM_022490:Homo sapiens hypothetical prot 3.68
414004 AA737033 Hs.7155 similar to thymidylate kinase family LPS 3.67
448595 AB014544 Hs.21572 KIAA0644 gene product 3.66
429922 Z97630 Hs.226117 H1 hlstone family, member 0 3.66
419440 AB020689 Hs.90419 KIAA0882 protein 3.66
439453 BE264974 Hs.6566 thyroid hormone receptor interactor 13 3.66
456508 AA502764 Hs.123469 ESTs, Weakly similar to AF2088551 BM-01 3.66
433701 AW445023 Hs.15155 ESTs 3.65
420390 AA330047 Hs.191187 ESTs 3.65
418661 NM 001949 Hs.1189 E2F transcripton factor 3 3.65
418203 X54942 Hs.83758 CDC28 protein kinase 2 3.64
434844 AF157116 Hs.22350 hypothetical protein LOC56757 3.63
424179 F30712 Hs.334573 Homo sapiens, clone IMAGE:4285740, mRNA 3.63
447350 AI375572 v-erb-a avian erythroblastic leukemia vi 3.60
444743 AA045648 Hs.301957 nudix (nucleoside diphosphate linked mol 3.60
430839 U67918 Hs.248049 fibroblast growth factor 10 3.60
422309 U79745 Hs.114924 solute carrier family 16 (monocarboxylic 3.58
439772 AL365406 Hs.10268 Homo sapiens mRNA full length Insert cDN 3.58
435664 AI032087 Hs.269819 ESTs 3.57
428134 AA421773 Hs.161008 ESTs 3.55
452092 BE245374 Hs.27842 hypothetical protein FLJ 11210 3.54
438869 AF075009 gb:Homo sapiens full length Insert cDNA 3.53
410555 U92649 Hs.64311 a disintegrin and metalloproteinase doma 3.53
452994 AW962597 Hs.31305 KIAA1547 protein 3.51
402496 Target Exon 3.51
429353 AL117406 Hs.335891 ATP-bindiπg cassette transporter MRP8 3.49
423419 R55336 Hs.23539 ESTs 3.48
441690 R81733 Hs.33106 ESTs 3.47
407235 D20569 Hs.169407 SAC2 (suppressor of actin mutations 2, y 3.47
412970 AB026436 Hs.177534 dual specificity phosphatase 10 3.45
400880 NM.000611*:Homo sapiens CD59 antgen p18 3.45
409456 U34962 Hs.54473 cardiac-specific homeo box 3.44
457579 AB030816 Hs.36761 HRAS-like suppressor 3.44
409430 R21945 Hs.346735 splicing factor, arginine/serine-rich 5 3.43
406922 S70284 Hs.119597 gb:stearoyI-CoA desaturase [human, adlpo 3.43
418304 AA215702 gb:zr97g10.r1 NCI.CGAP.GCB1 Homo sapiens 3.43
428479 Y00272 Hs.334562 cell division cycle 2, G1 to S and G2 to 3.43
444670 H58373 Hs.332938 hypothetical protein MGC5370 3.43
400277 Eos Control 3.42
440273 AI805392 Hs.325335 Homo sapiens cDNA: FLJ23523 fis, clone L 3.39
452833 BE559681 Hs.30736 KIAA0124 protein 3.39
413450 Z99716 Hs.75372 N-acetylgalactosaminidase, alpha- 3.39
453900 AW003582 Hs.226414 ESTs, Weakly similar to ALU8JUMAN ALU S 3.38
415402 AA164687 Hs.177576 maπnosyl (alpha-1,3-)-glycoprotelπ beta- 3.37
426931 NM 003416 Hs.2076 zinc finger protein 7 (KOX 4, clone HF.1 3.37
426384 A1472078 Hs.303662 hypothetical protein FLJ13189 (FLJ13189) 3.35
425782 U66468 Hs.159525 cell growth regulatory with EF-hand doma 3.35
420005 AW271106 Hs.133294 ESTs 3.35
425548 AA890023 Hs.1906 prolactπ receptor 3.35
441790 AW294909 Hs.132208 ESTs 3.35
429084 AJ001443 Hs.195614 splicing factor 3b, subunit 3, 130kD 3.34
446258 AI283476 Hs.263478 ESTs 3.34
420090 AA220238 Hs.94986 ribonuclease P (38kD) 3.33
439352 BE614347 Hs.169615 hypothetical protein FLJ20989 3.31
411558 AA102670 Hs.70725 gamma-amlnobutyrlc add (GABA) A recepto 3.30
444371 BE540274 Hs.239 forkhead box M1 3.30
437967 BE277414 Hs.5947 mel transforming oncogene (derived from 3.29
421305 BE397354 Hs.324830 dlptheria toxin resistance protein requl 3.29
406685 M18728 gb:Human nonspecific crossreactlng antlg 3.29
418478 U38945 Hs.1174 cyclln-dependent kinase Inhibitor 2A (me 3.28
401558 ENSP00000220478*:SECRETOGRANIN III. 3.28
407021 U52077 gb:Human marine transposasegene, comp 3.27
446054 AB014537 Hs.13604 KIAA0637 gene product 3.27
441020 W79283 Hs.35962 ESTs 3.26
441128 AA570256 ESTs, Weakly simllarto T23273 hypothet 3.24
447349 AI375546 gb:tc23d04.x1 Soares totaUetus_Nb2HF8 3.24
434378 AA631739 Hs.335440 EST 3.24
400295 W72838 AI905687:IL-BT095-190199-019 BT095 Homo 3.24
452206 AW340281 Hs.33074 Homo sapiens, clone IMAGE:3606519, mRNA, 3.23
443162 T49951 Hs.9029 DKFZP434G032 protein 3.22
427658 H61387 Hs.30868 nogo receptor 3.21
458621 AI221741 Hs.117777 ESTs 3.21 422938 NM 001809 Hs 1594 centromere protein A (17kD) 320
424871 NM.004525 Hs 153595 low density lipoproteln-related protein 320
410340 AW182833 Hs 112188 hypothetical protein FLJ13149 320
416294 D86980 Hs 79170 KIAA0227 protein 320
417386 AL037228 Hs 82043 D123 gene product 320
418004 U37519 Hs 87539 aldehyde dehydrogenase 3 family, member 320
444461 R53734 Hs 25978 ESTs, Weakly similar to 2109260A B cell 318
410174 AA306007 Hs 59461 DKFZP434C245 protein 317
408393 AW015318 Hs 23165 ESTs 317
426215 AW963419 Hs 155223 stannlocalcln 2 317
417771 AA804698 Hs 82547 retinolc add receptor responder (tazaro 316
453005 AW055308 Hs 31803 ESTs, Weakly simllarto N WASP [H saplen 315
413278 BE563085 Hs 833 Iπterferon stimulated protein, 15 kDa 315
441134 W29092 Hs 346950 cellular retinolc acld-blnding protein 1 314
420802 U22376 Hs 1334 v-myb avlan myeloblastosis viral oncogen 313
449746 AI668594 Hs 176588 ESTs, Weakly simllarto CP4Y.HUMAN CYTOC 313
417601 NM.014735 Hs 82292 KIAA0215 gene product 312
421654 AW163267 Hs 106469 suppressor of va (S cerevislae) 3 like 311
408877 AA479033 Hs 130315 ESTs, Weakly similar to A47582 B-cell gr 310
453511 AL031224 Hs 33102 AP-2 beta transcription factor 310
422981 AF026445 Hs 122752 TATA box binding protein (TBP)-assodate 310
413374 NM 001034 Hs 75319 πbonucleotlde reductase M2 polypeptide 310
449704 AK000733 Hs 23900 GTPase activating protein 310
427581 NM 014788 Hs 179703 KIAA0129 gene product 308
418329 AW247430 Hs 84152 cystathlonlne beta synthase 305
422010 AA302049 Hs 31181 Homo sapiens cDNA FLJ23230 (is, clone C 304
409892 AW956113 Hs 7149 gb EST368183 MAGE resequences, MAGD Homo 304
427674 NM 003528 Hs 2178 H2B hlstone family, member Q 304
431745 AW972448 Hs 163425 Novel FGENESH predicted cadhenn repeat 303
409757 NM.001898 Hs 123114 cystatin SN 303
417288 AI984792 Hs 108812 hypothetical protein FLJ22004 303
420111 AA255652 gbzs21h11 rl NCI CGAP GCB1 Homo sapiens 303
428771 AB028992 Hs 193143 KIAA1069 protein 303
408527 AL135018 Hs 33074 Homo sapiens, clone IMAGE 3606519, mRNA, 302
424001 W67883 Hs 137476 paternally expressed 10 302
420552 AK000492 Hs 98806 hypothetical protein 302
413063 AL035737 Hs75184 chitlnase 3 like 1 (cartilage glycoprote 301
410619 BE512730 Hs 65114 keratin 18 301
453902 BE502341 HS 3402 ESTs 301
423645 AI215632 Hs 147487 ESTs 300
442353 BE379594 Hs 9136 ESTs, Moderately similar to ALU7.HUMAN A 300
425842 A1587490 Hs 159623 NK-2 (Drosophila) homolog B 300
439680 AW245741 Hs 58461 ESTs, Weakly simllarto A35659 krueppel- 299
442530 AI580830 Hs 176508 Homo sapiens cDNA FLJ14712 (is, clone NT 299
430066 AI929659 Hs 237825 signal recognition particle 72kD 299
420649 AI866964 Hs 124704 ESTs, Moderately similar to S65657 alpha 298
437915 AI637993 Hs 202312 Homo sapiens clone N11 NTera2D1 teratoca 298
452256 AK000933 Hs 28661 Homo sapiens cDNA FLJ10071 fis, clone HE 298
433029 NM 014322 Hs 279926 opsln 3 (encephalopsln) 297
417924 AU077231 Hs 82932 cyclln DI (PRAD1 parathyroid adenomatos 297
455286 BE144384 gb MR0 HT0166-191199 004-C11 HT0166 Homo 295
437682 AA476652 Hs 94952 Homo sapiens cDNA FLJ23371 fis, clone H 295
408633 AW963372 Hs 46677 PRO2000 protein 295
401203 Target Exon 295
418675 AW299723 Hs 87223 bone morphogenetic protein receptor, typ 295
428166 AA423849 Hs 79530 M5 14 protein 295
440594 AW445167 Hs 126036 ESTs 295
430294 AI538226 Hs 32976 guanine nucleotide binding protein 4 294
434094 AA305599 Hs 238205 hypothetical protein PRO2013 294
412141 AI183838 Hs 48938 hypothetical protein FLJ21802 294
430289 AK001952 Hs 238039 hypothetical protein FLJ11090 294
441021 AW578716 Hs 7644 H1 hlstone family, member 2 293
439580 AF086401 Hs 293847 ESTs, Moderately similar to S65657 alpha 293
423198 M81933 Hs 1634 cell division cycle 25A 292
453751 R36762 Hs 101282 Homo sapiens cDNA FLJ21238 fis, clone C 292
412942 AL120344 Hs 75074 mitogen activated protein klnase-actvat 290
424036 AA770688 H2A histone family, member L 290
442711 AF151073 Hs 8645 hypothetical protein 290
427719 AI393122 Hs 134726 ESTs 289
443845 AI590084 ESTs, Weakly simllarto A47161 Mac-2-bιn 289
432731 R31178 Hs 287820 fibroπectin 1 289
444079 H09048 Hs 23606 ESTs 288
432728 NM 006979 Hs 278721 HLA class II region expressed gene KE4 288
422955 AW967824 Hs 324237 ESTs 288
432116 AA902953 Hs 308538 ESTs 288
427521 AW973352 ESTs 288
431127 U66618 Hs 250581 SWI/SNF related, matrix associated, actl 287
416636 N32536 Hs 42645 solute carrier family 16 (monocarboxylic 287
409703 NM 006187 Hs 56009 2'-5' ollgoadenylate synthetase 3 (100 k 287
440074 AA863045 Hs 10669 ESTs, Weakly simllarto T00050 hypotheti 287
411285 AI733766 Hs 69429 Homo sapiens IMAGE 512024 clone, mRNA 286
442772 AW503680 Hs 5957 Homo sapiens clone 24416 mRNA sequence 286
431566 AF176012 Hs 260720 J domain containing protein 1 285
405366 NM.003371* Homo sapiens vav 2 oncogene ( 285
414747 U30872 Hs 77204 centromere protein F (350/400kD, mltosln 285
452099 BE612992 Hs 27931 hypothetical protein FLJ10607 simllarto 283 405770 NM 002362 Homo sapiens melanoma antigen, 283
439024 R96696 Hs 35598 ESTs 283
420440 NM 002407 Hs 97644 mammaglobin 2 282
424339 BE257148 endoglycan 282
439574 AI469788 ESTs 282
438714 AA814859 ESTs 281
448789 BE539108 Hs 22051 hypothetical protein MGC15548 280
431546 L39211 Hs 259785 carnitne palmitoyltransferase I, liver 280
428898 AB033070 Hs 194408 KIAA1244 protein 280
452826 BE245286 Hs 301636 peroxisomal biogenesis factor 6 278
406277 Target Exon 278
423554 M90516 Hs 1674 glutamine-fructose-6-phosphate transamin 278
437108 AA434054 Hs 80624 hypothetical protein MGC2560 277
410275 U85658 Hs 61796 transcπpton factor AP-2 gamma (activat 277
405558 Target Exon 277
452620 AA436504 Hs 119286 ESTs 277
406625 Y13647 Hs 119597 stearoyl-CoA desaturase (delta-9 desatur 277
416128 AA173632 CDC14 (cell division cycle 14, S cerevi 276
448877 AI583696 Hs 253313 ESTs 276
431882 NM 001426 Hs 271977 engrailed homolog 1 275
411678 AI907114 Hs 71465 squalene epoxidase 275
449318 AW236021 Hs 78531 Homo sapiens, Similar to RIKEN cDNA 5730 275
433388 AI432672 Hs 288539 hypothetical protein FLJ22191 275
409178 BE393948 Hs 50915 kallikrein 5 275
409960 BE261944 hexokinase 1 274
408296 AL117452 Hs44155 DKFZP586G1517 protein 274
422559 AW247696 Hs 155839 hypothetical protein MGC12934 273
415889 R24563 VPS10 domain receptor protein 273
406043 Target Exon 273
440351 AF030933 Hs 7179 RAD1 (S pombe) homolog 273
411630 U42349 HS 71119 Putative prostate cancer tumor suppresso 273
421077 AK000061 Hs 101590 hypothetical protein 272
407204 R41933 Hs 140237 ESTs, Weakly simllarto ALU1.HUMAN ALU S 272
435532 AW291488 Hs 117305 Homo sapiens, clone IMAGE 3682908, mRNA 270
446163 AA026880 Hs 25252 prolactln receptor 270
412482 AI499930 Hs 334885 mitochondπal GTP binding protein 270
409235 AA188827 Hs 7988 ESTs, Weakly simllarto I38022 hypotheti 270
407242 M18728 gb Human nonspecific crossreactiπg antig 269
449349 AI825386 hypothetical protein FLJ21939 similar to 268
448552 AW973653 Hs 20104 hypothetical protein FLJ00052 268
404580 tnchorhinophalangeal syndrome I gene (T 268
416198 H27332 Hs 99598 hypothetical protein MGC5338 268
442643 U82756 PRP4/STK/WD splicing factor 267
422363 T55979 Hs 115474 replication factor C (activator 1) 3 (38 267
407137 T97307 gb ye53h05 s1 Soares fetal liver spleen 267
404076 NM.016020* Homo sapiens CGI-75 protein ( 267
447805 AW627932 Hs 302421 gemιn4 267
450256 AA286887 Hs 24724 MFH-arnpllfied sequences with leucine-πc 266
452834 AI638627 Hs 105685 KIAA1688 protein 266
439949 AW979197 Hs 292073 ESTs, Weakly simllarto ALU7.HUMAN ALU S 266
416677 T83470 Hs 334840 ESTs, Moderately similar to I78885 serin 265
434540 NM.016045 Hs 3945 CGI-107 protein 265
404857 ENSP00000215851* DJ930L11 1 (SIMILAR TO 265
450728 AW162923 Hs 25363 presenilm 2 (Alzheimer disease 4) 265
430452 AI888450 Hs 174644 hypothetical protein FLJ21669 265
425018 BE245277 Hs 154196 E4Ftranscripton factor 1 265
419767 W73306 Hs 306668 Homo sapiens cDNA FLJ14089 fis, clone MA 265
435124 AA725362 Hs 120456 ESTs 265
426919 AL041228 ELAV (embryonic lethal, abnormal vision, 265
407168 R45175 Hs 117183 ESTs 265
422880 AF228704 Hs 193974 glutathione reductase 263
409799 D11928 Hs 76845 phosphoserlne phosphatase-like 263
402102 Target Exon 263
452243 AL355715 Hs 28555 programmed cell death 9 (PDCD9) 263
429901 AK000502 Hs 56237 hypothetical protein FLJ20495 262
454425 AW300927 Hs 27192 hypothetical protein dJ1057B202 262
407792 AI077715 Hs 39384 putative secreted ligand homologous to f 261
407777 AA161071 Hs 71465 squalene epoxidase 261
451369 AA017321 Hs 269691 ESTs 261
432586 AA568548 ESTs 260
415632 U67085 Hs 78524 TcD37 homolog 260
419526 AI821895 Hs 193481 ESTs 260
400884 Target Exon 260
425671 AF193612 Hs 159142 lunate fπnge (Drosophila) homolog 260
425236 AW067800 Hs 155223 stanniocalcln 2 260
453507 AF083217 Hs 33085 WD repeat domain 3 259
423081 AF262992 Hs 123159 sperm associated antigen 4 258
422771 NM 012318 Hs 120165 leuclne zlpper-EF-hand containing transm 258
419589 AW973708 Hs 201925 Homo sapiens cDNA FLJ13446 fis, clone PL 258
403006 NM.006933* Homo sapiens solute carrier f 258
453785 AI368236 Hs 283732 ESTs, Moderately similar to ALU1 HUMAN A 258
418437 AA771738 Hs 348000 ESTs, Moderately similar to ALU5.HUMAN A 258
436211 AK001581 Hs 334828 hypothetical protein FLJ10719, KIAA1794 258
406627 T64904 Hs 163780 ESTs 257
431130 NM 006103 Hs 2719 HE4; epldidymls-speclfic, whey-acldlc pr 257
424308 AW975531 Hs 154443 mlnlchromosome maintenance deficient (S 257 404982 Target Exon 256
453968 AA847843 Hs 62711 High mobility group (nonhistone chromoso 256
412673 AL042957 Hs 31845 ESTs 256
433848 AF095719 Hs 93764 carboxypeptdase A4 256
434815 AF155582 Hs 46744 Corel UDP-galactose N-acetylgalactosamln 255
454110 AA195509 Hs 39733 postsynaptic protein CRIPT 255
418617 AA225849 Hs 83419 ESTs, Moderately similar to ALU8.HUMAN A 255
410507 AA355288 transitional epithelia response protein 255
442326 H92962 Hs 124813 hypothetical protein MGC14817 255
454453 AW752781 hypothetical protein FLJ 12614 similar to 254
430316 NM 000875 Hs 239176 Insulin like growth factor 1 receptor 254
442961 BE614474 F-box only protein 22 253
428484 AF104032 Hs 184601 solute earner family 7 (cationic amino 253
430375 AW371048 Hs 93758 H4 hlstone family, member H 253
423250 BE061916 Hs 125849 chromosome 8 open reading frame 2 253
440006 AK000517 HS 6844 NALP2 protein, PYRIN-Contalnmg APAF1-II 253
426098 NM 014906 Hs 166351 KIAA1072 protein 253
415857 AA866115 Hs 127797 Homo sapiens cDNA FLJ11381 fis, clone HE 253
426108 AA622037 Hs 166468 programmed cell death 5 252
425159 NM 004341 Hs 154868 carbamoyl-phosphate synthetase 2, aspart 252
422390 AW450893 Hs 121830 ESTs, Weakly similar to T42682 hypotheti 252
411605 AW006831 ESTs 251
421690 AW162667 Hs 106857 calblndln 2, (29kD, calretinln) 251
452827 AI571835 Hs 55468 ESTs 250
431958 X63629 Hs 2877 cadheπn 3, type 1, P-cadheπn (placenta 250
459376 BE258770 Homo sapiens, clone IMAGE 3344506, mRNA, 250
452335 AW188944 Hs 61272 ESTs 250
447397 BE247676 Hs 18442 E-1 enzyme 250
426991 AK001536 Hs 214410 Homo sapiens cDNA FLJ10674 fis, clone NT 250
414915 NM 002462 Hs 76391 myxovirus (influenza) resistance 1, homo 250
TARI F 9B Pkey Unique Eos probeset Identifier number
CAT number Gene cluster number
Accession Genbank accession numbers Pkey CAT number Accession
400291 1314911 1 AA927862 AA401369 AI873274 400205 2538.1 NM.006265 D38551 X98294 BM477931 BM461566 AU123557 AU133303 AU134649 AW500421 BM172439 AW500587 AW503665
AW504355 AW503640 BM152454 AW505260 AI815984 AW504075 AW500716 AL597310 BC001229 BM474371 AA984202 AU135205
BE090841 AW163750 BF747730 BF898637 AI206506 AV660870 AV692110 AW386830 AV656831 N84710 AW993470 BF086802
BF758454 BG960772 BF757769 BI870853 BE018627 C75436 AW148744 BF757753 BG622067 BE909924 AA708208 BG530266 BF968015
AW992930 BF888862 BG536628 AA143164 AW748953 BG498922 BF885190 BF889005 BF754781 BF800003 BM476529 AI627668
AW028126 AL046011 BF590668 AI017447 AA579936 AI367597 AA699622 BE280597 AI124620 AI082548 AW274985 AA677870 AI056767
BE551689 AA287642 H94499 AI752427 AI652365 AW002374 AW062651 AA360834 N68822 AU135442 AU125960 Z78334 BE545813
AI092115 BF312771 BF242859 BG533616 BG533761 BG164745 BG492433 BM473183 AA172043 AA172069 AU157092 AU151353
AU155318 BE302211 AI375022 AA085641 AU157923 H88858 AA132730 AA115113 AA909781 AI475256 AA424206 AW572383 AW084296
AI184820 AI469178 AA782432 H92184 AA340562 BF195818 AA852821 AW576342 AA827107 AA173317 AW190014 AI918514 AA729372
AA729718 AI055958 AA331424 BE328601 AA515690 BI018896 AW628277 AA748368 AA626222 BG492636 AW380620 BF800058
AW370956 AA290909 R25857 BG952995 BF801437 AA172077 AU155890 AU149783 AI720904 AA902936 AA865727 AI470830 AV740677
AA142982 AA482485 AU145485 AW576399 AU156042 R63448 BF246427 BE928472 D25910 BF758439 BF968785 BE565238 AA355981
AI905607 BG291148 BG533096 BG532888 BF030886 BG613756 BE928471 BG574501 AA187596 AA361196 T95557 BG531446
BG527242 BG527513 BG611106 AA085995 BF847252 BG024608 BE540261 BG531236 AL579993 BG108733 BG483503 BG571032
BG492505
407178 683007.1 AW235123AA195651 458098 23945.1 AI082245 BE467534 AI797130 BE467063 BE467767 BE218421 AI694996 BE327781 BE327407 BE833829 AA989054 AA459718 BE833855
BE550224 AA832519 AF086393 AV733386 BE465409 N29245 W07677 AA482971 BE503548 H18151 AA461301 W79223 W74510
AI090689 AL600773 AL600781 N46003 R28075 R34182 BE071550 AW885857 AI276145 AI276696 H97808 N20540 AI468553
451807 17758.2 BM479185 AL552795 AL577722 BF038888 BM127617 BF510346 AW450652 AA865478 AW449519 BM127314 AI806539 AW449522
AA993634 AI827626 AA904788 428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 A1928140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658
AA769094 BF446026 AW118719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704
AI356361 AI923640 AW070509 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311
AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 B1061872 BI059498 AA134476
AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166
427365 1314911.1 AA927862AA401369AI873274 426878 1026976.1 AL044891 AI908240 AA393080 AW748403 BE069341 BF330573 433023 3970.8 BE999967 BF438599 AW864793 AI802899 BE815132 AW468888 AI672189 A1052004 BF112024 AA772335 AW275054 AA573845
A1144148 AI968683 AA846676 AA927355 H80424 AW973295 R88209 F29868 BE928871
424399 2196.1 NM.058173 AF414087 W72837 BF742809 AW070916 BE092421 AI905687 AA340069 BE074512 AI905623 AI905633 BG202312 W72838
AI139456 BG218084 BE926938 BE186013 AW176044 AW291950 BG185269 BG197186 BG192597 BG183176 BG207535 AI127172
BE815819 AI905624 R75793 BG202313 AI905837 BE815853
419536 251846.1 AA244095 AA603305 AA244183 415989 10194.1 BC013389 BC017398 AI023543 AA191424 AI267700 AI469633 AW958465 AW953397 AA172056 BE940298 BF909208 BF909980
BF095153 BG285837 AI720344 BF541715 AA355086 AA172236
453160 6028.5 BC009612 NM.003526 BI597616 AV761592 AV760377 AL601008 BI604131 BE645918 BG187760 BG181525 BG210634 BG192999
AI263307 AA344186 AW952966 AA033609 AA037562 AA722183 R79452 H70775 BF674991 BE769437 BG007856 AA037483 AW572535
AI143991 AA084581 AA033610 AV742510 AV735788 R08336
443695 20416.12 BE535598 AW204099 AW301249 AA609749 BF917914 AA775742 AV646137 AV646389 AA314747 451752 10408.5 AB032997 AI141678 AW978722 BE467119 AI761408 BF727385 AW237035 AI934521 BF436248 AI479668 Z40632 AA832081 AW295901
BF057835 BE465977 AI621269 BE465983 BF756369 N74056 AI817896 AA716567 AA934774 H62600 H09497 BF943762 BE395335
BE883333 437834 294580.1 BG110129 AW749287 BE535498 AW749299 AW749293 AW749302 AW749298 AW749291 AW749294 AW749289 AW749288 AW749296
AA769294 AW749297 AW749295 AW749292 BE002573 70312.1 AA151520 AI749635 AA149436 BE172702 AW317084 AA922501 AI302818 AI147563 AA789216 AI719336 AW612978 F34536 AI971386
A1246525 AI183312 R02554 AI360172 AA634282 AI022935 AA639461 AI086411 AI087086 AA633082 AI590029 AA856582 AW369734
AA150042 AA877171 AA456459 AI078529 R83333 A1161298 AA056987 AI350120 H88127 AA258759 AI673598 AA454566 AI342790
AI492606 AI159945 AI198009 AI198039 AI142751 AI141403 T81478 AW014110 AI197808 AI927796 AA534936 AA649735 AA649697
AI349452 AA719660 AW954285
447350 2267324.1 AI375572 AI480404 BF430912 T06882
438869 52134.1 AF075009 R63109 R63068
418304 1093209.1 BE883520 BI057842 AA215702 AA215703 AA368006 BE006876 BE066555
400277 170.1 Y00281 NM.002950 BC010839 BC007995 BG675232 BM468552 AL555484 BG831516 BF035300 BG677277 BF852972 BE314901
BF850656 AI371816 AA292474 AA375747 AA308414 BM454544 BI333370 BM049921 BI461428 BI465007 BI223401 BE856245 AW821164
BF914775 BF914761 AU125835 BI222678 BI091137 BF340536 BM462798 BI224452 BG707915 AL569160 AA443815 AW572867
AW363410 BF739268 BG010283 BI013120 BF818845 BF763468 AA305165 AI630370 AA039826 R24906 H02046 T96891 BF981330
AW936510 AA478169 H04587 BG166574 B1869342 BE562482 BE539637 AA165089 AL579118 AL553699 BE044054 AW117440 AI520674
BF435417 AW245648 AI952404 T29534 AU153459 AU152168 AW591591 AU146918 AI393187 AA478013 AU148143 AI224471 A1640728
AI871537 AW264752 N93787 AI189357AV756134AI471659AU147466 AA779206 AU149419AU149104 AU159135 AA312221 AW445119
AW021912 AI799771 F04407 AI285530 AI914643 AW068751 AA513325 AA164627 AA639285 AA569644 T96892 AI923594 BF439180
BI770936 BF032438 AU154884 AA682793 AW072992 AU158815 AI884444 AL048031 AU158922 AU152546 AI695187 AL048033 AI245650
AU148507 AW467451 BE536868 BF913001 BF062707 AL573082 AW067993 AA523354 BE886727 AI890705 AU159092 AI982693
AI817553 AA236729 AI687858 BG163767 AI524675 AI678155 AA127100 AI762661 AU159718 AI469720 AA483627 AW131696 R26868
AI199885 AW875614 AW938694 AW578974 BI763988 BG819168 BE874767 BG978292 BE162948 AL555483 AW189719 T56783 AI018819
AI476552 BI492837 AI824440 BG996262 AA932887 AI380726 R79530 AA622108 AI262575 T56782 R27437 BE784153 AW129549
AI675567 AI866759 BG987935
406685 0 0 M18728
407021
441128 20932 1 BC014072 BE328850 AI356567 AI148171 AI022165 BG149661 BF000671 AA233101 AA573721 AA447991 AW016855 AI005068 AA554071
BF478215 AA906902 AW014761 BE905651 BE512923 BM047129 AA243852 AA232991 AA127550 AA127551 AA570256 AI473237
BF033706 N90525 AW973623 AI359627 BG674574 BE903322
447349 1063443.1 BE743847 AW809603 BM469626 AI375546 400295 2196.1 NM 058173 AF414087 W72837 BF742809 AW070916 BE092421 AI905687 AA340069 BE074512 AI905623 A1905633 BG202312 W72838
AI139456 BG218084 BE926938 BE186013 AW176044 AW291950 BG185269 BG197186 BG192597 BG183176 BG207535 AI127172
BE815819 AI905624 R75793 BG202313 AI905837 BE815853
420111 256912.1 AW967920 AA262684 AA255652 AA280911
455286 1149378.1 W27935 AW887403 AW887474 BE144384 BE144386 424036 6226 1 NM.033445 BC001193 AI885781 BF794032 AA476620 AA810906 AA810905 AI291244 AI885097 AI359708 AI335629 H97396 AI344589
AA300377 AA457566 AW771833 BE465621 AI364068 A1364452 AI648505 AI918342 AI928670 AA886580 AL531029 AA886344 A1186419
BG329096 BM045465 AL531028 BG437151 BE868021 AA179427
443845 507824.1 BG394808 BE858105 AI569728 AI590084 BE223011 AW007054 AI554692 AI939398 AW014243 AI088747 AI498970 AI199622 BF115458
BI714844 BI715424 AW135964 BG470892 BF347984 AI569769 AI424675 AI939616 BF116017 BF513472 AI828151 AI199676 AW139725
AI475044AI128872
427521 513212.1 AW973352 BF222929 AW016853 BF059130 AI651829 BE551767 AA558414 AI339359 BF059601 AI961162 AI341422 AI206248 AI206165
AA548736 AA768578 AI539081 AW025957 AA736837 N79575 AW594357 AA480892
424339 50559 1 NM.015720 AF219137 AL534420 AL524055 AL537346 AL538442 BG765888 AL530054 AL525377 BG474596 BG473144 BE251553
BG706099 AL538039 BG703131 BE255806 BF805256 F12128 AL566773 BI828686 BF761480 AI204971 BG818818 BI199246 AL534816
BF529941 AA324163 AL523285 BG914330 H07952 AL534815 BE769903 AI867802 BM310135 AL533702 BE254484 BF528852 BE867462
BE740130 AL134164 AL567115 AL533701 AL524054 AL515904 AL523284 AL568203 AL534419 BF981162 BE257148 AL561833
439574 689966.1 BG532820 AW246001 AI469788 AI350090 AI446788 BE549330 W84862 AA837988
438714 2576235.1 AA814859 AI582623AA814857
416128 3761.6 AK057803 BG944795 AW411505 AW949210 BI018336 AI366964 BE165417 AA173988 BF965882 AA581362 AI002701 AA340708
BF762925 BE005389
409960 39576.1 BE644758 AI082238 BF940027 AI201079 AI436035 AW275966 AI085394 AI291655 AW070441 AI474134 AI268978 AI769279 AI567682
AA693941 BF477668 AW664149 AA283782 BF509538 AW296868 AI268977 AI168133 BM352065 AI262769 BF941976 AI056920
AA481861 BF763697 AL565888 BM352383 AA427768 AA385346 AI186988 AA931831 AA134972 BF217480 BF111012 AA908246
AA319849 AA318136 AL514271 BF364291 AL515057 AV702312 AA377395 AL544217 AI341000 AW193583 AI350789 AA888338
BF945380 AW879092 AA130839 T91066 N92326 AI004389 AA078832 AL572370 W04622 BE314003 AW960808 BM360872 AA319160
AA130778AL514257
415889 12922.1 NM.052918 AF284756 BE019093 Z42986 BE328250 BE207835 R54516 R24563 H08127 BI522616 AA551620 H07879 AI174481 BF941262
BF222810 R54417 AW137766 AI638502 N22373 H08128 R44366 AW272405 A1675836 Z38786 N75618 F02463 AI654047 B1492031
AW021081
407242
449349 852.3 BG679689 AW856638 BM016319 BE327123 AW772128 BE693337 BE938262 BG013928 BF892774 BF894765 BF892588 BF890995 BE155056 BE153569 AI934407 BE672538 AW204203 AA778306 BE502974 AI718504 AA778312 AW008224 AW299732 AI911561 AI867457 AI521962 AI640173 AI823832 AI288888 BE467960 AI934441 AA483527 AW612103 AI802712 AW342106 AI580299 AW083293 A1700874 AW469932 A1583726 AW302136 BE327360 AW614404 C02300 AA934834 F29737 AI262050 AA934619 AA535965 BF196507 AA393480 BF086615 AI825386 AA009773 B1333272 T93614 AW770207 BF766665 T64641 W92713 R94110 T89897 BF086603 T93659 AA001207 BE539257 BE541430 BE160783 BE155304 BE155454 BF891405 BF762818
442643 2736. BC001588 BC007424 AF016369 NM.004697 BI756186 BE257019 BG500792 BI862776 AL121371 BG574833 AA703250 AA179511 AW052006 AI280150 A1914000 AI358319 AI081204 AI082594 AA992449 AI470821 AI655744 AW237529 AA678858 AI984430 BF433055 BE467594 BE467573 AA035630 AI289987 AI184802 AI681391 AW592416 AI138377 AI139266 AA961714 AI800163 AA418751 AW451928 AA668676 AI273444 AI494387 BE046912 AI276555 BF196021 AA700055 AA609305 AA772596 AI635758 AI635749 H95459 AW610290 BE464994 AA527136 BF374802 AI800175 AW195227 AI189676 BF802049 AL513632 AL554911 AL538845 BE297273 AA315321 BM451920 BE269268 BE292835 BE018128 BG755713 BM041095 BG677009 AL039691 BF995709 BE735586 BE296453 BG393609 BG824453 AL567522 AI745257 AW388641 AW301265 AI141144 AW029280 AU149362 AU152328 AA418960 AL121009 AI890398 AL528748 H1305O T47086 BI000575 BF334914 BF109661 R44450 H13259 T47087 AW388646 BF305834 AL577515 BM041600 BE889299 BF239768
407137
426919 347372 1 BI917595 AI203314 AL041228 AV727959 D61361 D82004 BI753157 AA961066 AI990307 BF439651 AI453076 AI376075 AI014836
AI018308 AW183530 AA393346 AA935601 AA628633 AI150282 AI028574 AI217182 AA431478 AW087473 AW900295 H50055 AL041229
B1917726
432586 6633 1 BC022881 AU150944 BG750783 AW754175 AW857737 AI911659 AI050036 AA554053 AI826259 AA568548 410507 4450.2 AK027433AF117064 NM.013319 BC004468 AI149901 A1150093A1374696 AI566580 AA779898 BG696067 BG828923 BM051241
BM050350 AL580560 AL558826 BG182261 BG194259 BG194258 BF036155 AI026803 AI024570 AA702281 AI566953 AW662600
AA463546 F33147 AA357796 BE312357 AL516788 AW958856 BE730432 H85868 AA046292 BG478025 BG112231 BG763623 AA098922
BI093481 BE746381 AW962126 AI040821 BG026983 AA355288 BE392859 AA085571 BF875433 BF316280 BG740116 BG166624
454453 8582.4 BF313069 BE879305AW752781 AW752727AW752559AW752578AW752584 BF846118AL545903 BF846115AL525361 442961 60316.2 BE966247 BE220885 BE467384 BE350135 BE672094 AI811582 AW665254 AA772731 AI283601 AA417067 AW197746 AI868357
AI792143 AA931120 AI758506 AA843761 BE737582 AW379586 N38812 BG567321 H13257 411605 10026.3 BG256892 H10532 N46614 R52610 AW977696 BM460488 W56819 BI042183 BG977498 BE767451 BF870009 BG477472 R61137 R14274
R20259 R09686 BI838226 BF034269 AA429173 BE741829 AW867495 AI123683 AW006831 BE831162 AW452753 AV742717 W86152
BF115102 AI633815 BF921562 AA094230 BE092587 W86151 AA526153 AI672156 BF914496 R12579 BF852352 AA699780 T57386
BF903022 09933AA678298
459376 31010.1 BC002465 BE254864 BG472164 BE258770 TABLE 2C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers in this column are Genbank Identifier (GI) numbers 'Dunham I et al " refers to the publication entted "The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495 Strand Indicates DNA strand from which exons were predicted Nt_posιtιoπ Indicates nucleotide positions of predicted exons
Pkey Ref Strand Nt_posιtιon
404561 9795980 Minus 69039-70100
401451 6634068 Minus 119926-121272
401519 6649315 Plus 157315-157950
403485 9966528 Plus 2888-3001,3198-3532,3655-4117
401464 6682291 Minus 170688-170834
401866 8018106 Plus 73126-73623
404571 7249169 Minus 112450-112648
400528 6981824 Plus 472381-472528,474170-474277,475328-47554
404632 9796668 Plus 45096-45229
402496 9797769 Minus 8615-9103
400880 9931121 Plus 29235-29336,36363-36580
401558 7139678 Plus 103510-104090
401203 9743387 Minus 172961-173056,173868-173928
405366 2182280 Plus 22478-22632
405770 2735037 Plus 61057-62075
406277 5686030 Minus 4759-5490
405558 1621110 Plus 4502-4644,59836083
406043 6758938 Plus 36609-37156
404580 6539738 Minus 240588-241589
404076 9931752 Minus 3848-3967
404857 5304923 Plus 111653-111816,114925-115007
402102 8117771 Minus 174566-174740
400884 9958187 Minus 57979-58189
403006 5881378 Plus 4410846264
404982 4432779 Plus 30375-30743,32569-32719,33698-33808
TABLE 3A About 216 oβnes upregulated In breast metastases to the hrain relative to nπmarv breast tumors
Pkey Unique Eos probeset identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentle of breast metastases to the brain Als divided by the 90th percentile of breast tumor Als, where the 15th percentile of all normal body
Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
422756 AA441787 Hs 119689 glycoprotein hormones, alpha polypeptde 1029 37 419875 AA853410 Hs 93557 proenkephalin 1001 31 446292 AF081497 Hs 279682 Rh type C glycoprotein 683 73119 418678 NM.001327 Hs 167379 cancer/testis antigen (NY ESO 1) 646 2895 429504 X99133 Hs 204238 lipocalin 2 (oncogeπe 24p3) (NGAL) 586 56111 407168 R45175 Hs 117183 ESTs 562 7 421948 L42583 Hs 334309 keratin 6A 545 35100 415262 H95572 Hs 206521 YME1 (S cerevisiae) like 1 530 23 446787 U67167 Hs 315 mucln 2, intestinal/tracheal 5 18 74120 419078 M93119 Hs 89584 Insulinoma associated 1 495 2996 406643 N77976 Hs 347939 hemoglobin, alpha 2 495 410407 X66839 Hs 63287 carbonic anhydrase IX 489 421690 AW162667 Hs 106857 calblndin 2, (29kD, calretinln) 485 428434 AW363590 Hs 65551 Homo sapiens, Simllarto DNA segment, Ch 465 430294 A1538226 Hs 32976 guanine nucleotide binding protein 4 459 409178 BE393948 Hs 50915 kallikreiπ 5 447 433272 AB043585 Hs 100890 candidate mediator of the p53 dependent 444 431667 AA812573 Hs 246787 ESTs 442 431882 NM.001426 Hs 271977 engrailed homolog 1 438 428865 BE544095 Hs 164960 BarH like homeobox 1 402 453439 AI572438 Hs 32976 guanine nucleotide binding protein 4 400 443171 BE281128 Hs 9030 TONDU 393 414166 AW888941 Hs 75789 N myc downstream regulated 392 422799 AI933199 Hs 120911 neurexophllm 4 391 406690 M29540 Hs 220529 carcinoembryonic antgen related cell ad 382 422158 L10343 Hs 112341 protease inhibitor 3 skln-denved (SKAL 371 406791 AI220684 Hs 347939 hemoglobin, alpha 2 370 440475 A1807671 Hs 24040 potassium channel, subfamily K, member 3 359 407014 U38268 gb Human cytochrome b pseudogene, partia 356 409020 AA062549 Hs 21162 retbindin 353 417366 BE185289 Hs 1076 small praline πch protein 1B (comifin) 352 457029 AA397789 Hs 161803 ESTs 350 437433 R74016 Hs 121581 ESTs 345 424998 U58515 Hs 154138 chltinase 3 like 2 334 428342 AI739168 Homo sapiens cDNA FLJ13458 fis, clone PL 332 418951 F07809 Hs 89506 paired box gene 6 (anindia keratitis) 320 405452 Target Exon 3 19 428093 AW594506 Hs 104830 ESTs 3 16 443219 AI354669 Hs 187461 ESTs, Weakly simllarto C29149 praline r 3 15 440449 AA885430 Hs 201925 Homo sapiens cDNA FLJ13446 fis, clone PL 315 428648 AF052728 Hs 188021 potassium voltage-gated channel, subfaml 3 14 423226 AA323414 Hs 146109 ESTs, Weakly similar to T28937 hypotheti 3 14 429259 AA420450 Hs 292911 Plakophllln 3 14 447946 AI566164 Hs 277445 ESTs 313 413597 AW302885 Hs 117183 ESTs 3 10 401151 Target Exon 309 419138 U48508 Hs 89631 ryanodine receptor 1 (skeletal) 308 437679 NM.014214 Hs 5753 inosltol(myo)-1(or4) monophosphatase 2 307 406947 L10403 Hs3134 DNA binding protein amplifying expressio 306 425057 AA826434 Hs 1619 achaete scute complex (Drosophila) homol 304 443537 D13305 Hs 203 cholecystoklnln B receptor 303 403364 Target Exon 302 406716 AW148546 Hs 169476 glyceraldehyde-3 phosphate dehydrogenase 299 422997 BE018212 Hs 122908 DNA replication factor 296 422168 AA586894 Hs 112408 S100 calcium binding protein A7 (psorias 296 449077 AW262836 Hs 252844 ESTs 295 422010 AA302049 Hs 31181 Homo sapiens cDNA FLJ23230 fis, clone C 294 422256 M64673 Hs 1499 heat shock transcription factor 1 294 428484 AF104032 Hs 184601 solute carrierfamlly 7 (catonlc amino 294 412560 R24601 CCR4-N0T transcription complex, subunit 291 447349 AI375546 gb tc23d04 x1 Soares_total_fetus_Nb2HF8_ 291 406016 Target Exon 290 425371 D49441 Hs 155981 mesothelln 289 443672 AA323362 Hs 9667 butyrobetalne (gamma), 2-oxogIutaratedl 288 430147 R60704 Hs 234434 hairy/enhancer of spilt related with YRP 287 403246 Target Exon 286 424047 AI868401 Hs 138248 hypothetical protein YH95C04 285 450256 AA286887 Hs 24724 MFH amplified sequences with leucine ric 285 452800 U10991 Hs 30660 G2 protein 284 435408 H07897 Hs 4302 ESTs, Weakly simllarto T29299 hypotheti 282 434567 AK000600 Hs 3972 NeuAc-alpha-2,3 Gal-beta-1,3 GalNAc-alph 281 450149 AW969781 Hs 132863 Zlc family member 2 (odd-paired Droεophl 281 409456 U34962 Hs 54473 cardiac-specific homeo box 279
429986 AF092047 Hs 227277 sine oculis homeobox (Drosophila) homolo 279
412383 AW947577 gb RC0-MT0004-140300 031-b09 MT0004 Homo 278
431130 NM 006103 HS 2719 HE4, epldldymls-specific, whey-acldlc pr 277
445707 AI248720 Hs 114390 ESTs 275
449709 BE410592 Hs 23918 hypothetical protein PP5395 274
403140 Target Exon 274
453309 AI791809 Hs 32949 defensin, beta 1 273
423166 AB035334 Hs 144181 ESTs 272
413027 NM 002885 Hs 75151 RAP1, GTPase activating protein 1 271
447866 AW444754 Hs 202095 ESTs 270
437044 AL035864 Hs 69517 differentially expressed in Fanconi's an 270
403669 Target Exon 268
420783 AI659838 Hs 99923 lectn, galactoslde-binding, soluble, 7 266
406685 M18728 gb Human nonspecific crossrea lng antig 264
405151 Target Exon 262
426006 R49031 Hs 22627 ESTs 261
424066 Z99348 Hs 112461 ESTs, Weakly simllarto I38022 hypotheti 261
424250 AF073310 Hs 143648 Insulin receptor substrate 2 261
407737 R49187 Hs 6659 ESTs 260
448296 BE622756 Hs 10949 Homo sapiens cDNA FLJ14162fis, clone NT 260
440232 A1766925 Hs 112554 ESTs 260
420767 AF072711 Hs 99918 carboxyl ester lipasβ (bile salt-stimula 259
420230 AL034344 Hs 284186 forkhead bo d 258
406835 A1318327 gb ta42c10 x1 NCI_CGAP_Lu25 Homo sapiens 268
413063 AL035737 Hs 75184 chitinase 3-lιke 1 (cartilage glycoprote 258
443845 AI590084 ESTs, Weakly simllarto A47161 Mac-2-bln 257
412968 AW500508 Hs 75102 alanyl-tRNA synthetase 257
452786 R61362 Hs 106642 ESTs, Weakly simllarto T09052 hypotheti 257
425352 NM 000939 Hs 1897 praopiomelanocortln (adrenocortcotropιn 256
419767 W73306 Hs 306668 Homo sapiens cDNA FLJ14089 fis, clone MA 255
437142 AI791617 Hs 145068 ESTs, Moderately similar to A46010 X-lln 255
401590 Target Exon 255
407147 D20425 gb HUMGS01399 Human promyelocyte Homo sa 255
422559 AW247696 Hs 155839 hypothetical protein MGC12934 255
426686 AI362802 Hs 171814 parathymosm 254
412452 AA215731 suppression of tumoπgeπlclty 5 254
407242 M18728 gb Human nonspecific crossreactng antlg 253
446342 BE298665 Hs 14846 solute carπerfamlly 7 (cationic amino 253
424286 AA338285 Hs 90744 proteasome (prosome, macropaln) 26S subu 253
412796 U52426 Hs 74597 stromal interaction molecule 1 252
419589 AW973708 Hs 201925 Homo sapiens cDNA FLJ13446 fis, clone PL 251
433701 AW445023 Hs 15155 ESTs 249
429538 BE182592 Hs 139322 small proliπe-rich protein 2A 248
404645 C9001365* gi|2921630|gblAAC396121| (U86 248
422726 U11690 Hs 1572 faclogenital dysplasia (Aarskog-Scott sy 248
424347 AA723883 Hs 302446 hypothetical protein MGC10334 247
414580 BE386918 gb 601275386F1 NIH.MGC.20 Homo sapiens c 246
439477 W69813 Hs 58042 Homo sapiens GDNF family receptor alpha 245
422424 AI186431 Hs 296638 prostate differentiation factor 245
434861 AA206153 HS 4209 mltochondnal πbosomal protein L37 245
421661 BE281303 Hs 299148 hypothetical protein FLJ21801 245
406102 gb RC3-HT0273-120200014-C07 HT0273 Homo 244
424463 AW195353 Hs 119903 ESTs 244
431912 AI660552 ESTs, Weakly simllarto A56154 Abl subst 244
454453 AW752781 hypothetical protein FLJ12614 similar to 243
406718 AA505525 Hs 169476 glyceraldehyde-3-phosphate dehydrogenase 243
438364 AK000860 Hs 6191 hypothetical protein DKFZp762H66 242
436608 AA628980 Hs 192371 down syndrome cπtcal region protein DS 242
428182 BE386042 Hs 293317 ESTs, Weakly simllarto GGC1.HUMAN G ANT 242
419648 T73661 Hs 91877 thyroid hormone responsive SPOT14 (rat) 242
426067 AW664691 Hs 97053 ESTs 241
437026 AW976573 ESTs 241
405003 Target Exon 240
429749 A1685174 Hs 22293 ESTs, Weakly simllarto MUC2.HUMAN MUCIN 240
413934 U03056 Hs 75619 hyaluronoglucosamlnldase 1 240
426514 BE616633 Hs 170195 bone morphogenetlc protein 7 (osteogenlc 239
436557 W15573 Hs 5027 ESTs, Weakly similar to A47582 B-cell gr 238
406175 C1002017* gi|6678229lreflNP_033349 1| T- 238
414719 U66619 Hs 71622 SWI/SNF related, matrix associated, a i 238
400914 ENSP00000228091* Calcium-binding protein 237
449853 AF006823 Hs 24040 potassium channel, subfamily K, member 3 236
401612 C4000495 gl|6677633|ref|NP_033595 1| zln 236
457739 AF161337 Hs 283928 Homo sapiens HSPC074 mRNA, partial eds 236
456736 AW248217 Hs 1619 achaete-scute complex (Drosophila) homol 236
407119 AA167051 Hs 252040 EST, Moderately simllarto ZN91 HUMAN Zl 234
427715 BE245274 Hs 180428 KIAA1181 protein 234
402961 Homo sapiens mRNA, cDNA DKFZp761E0611 (f 233
447544 AA401573 Hs 288284 hypothetical protein FLJ22378 233
416135 AW473656 Hs 227277 ESTs 233
427722 AK000123 Hs 180479 hypothetical protein FLJ20116 233
444590 AA457456 hypothetical protein FLJ20435 232
432886 BE159028 Hs 279704 chromatin accessibility complex 1 232
409108 AA339443 Hs 48793 sialyltransferase 6 (N-acetyllacosamlnld 231
411410 R20693 Hs 69954 lamlnln, gamma 3 231
403828 C4000447* gl|7705570|ref|NP_038851 1| Kl 231 426350 NM 003245 Hs.2022 transglutamiπase 3 (E polypeptide, prate 2.31
431745 AW972448 Hs.163425 Novel FGENESH predicted cadherin repeat 2.31
424462 AU076666 Hs.148101 serum constituent protein 2.30
430176 AL161995 Hs.234775 neurturin 2.30
425707 AF115402 Hs.11713 E74-llke factor 5 (ets domain transcript 2.30
440313 AL050060 Hs.7158 D FZP566H073 protein 2.30
417017 AA976064 Hs.180842 ribosomal protein L13 2.30
426207 BE390657 Hs.30026 HSPC182 protein 2.29
424142 AI678727 Hs.75106 clusteriπ (complement lysis Inhibitor, S 2.29
440747 AW297226 Hs.137840 ESTs, Moderately similar to SIX4.HUMAN H 2.29
421574 AJ000152 Hs.105924 defensin, beta 2 2.28
402943 C20000263:gl|11436283|ref|XP_006959.1| g 2.28
402160 Target Exon 2.28
425140 AB014567 Hs.154740 TBP-lnteracting protein 2.28
435124 AA725362 Hs.120456 ESTs 2.28
416733 BE243319 Hs.79672 KIAA0652 gene product 2.27
459299 BE094291 Hs.155651 hepatocyte nuclear factor 3, beta 2.27
452833 BE559681 Hs.30736 KIAA0124 protein 2.27
429578 AI969028 Hs.99389 ESTs 2.27
417900 BE250127 Hs.82906 CDC20 (cell division cycle 20, S. cerevl 2.27
429469 M64590 Hs.27 glyclne dehydrogenase (decarboxylatng; 2.26
433472 AI541246 Hs.3343 phosphoglycerate dehydrogenase 2.26
429849 U33053 Hs.2499 protein kinase C-llke 1 2.26
402463 NM 014624:Homo sapiens S100 calclum-blnd 2.26
408595 AI925900 Hs.178715 ESTs, Weakly similar to TRHY.HUMAN TRICH 2.26
427486 AA974433 fibroblast growth factor 4 (heparin seer 2.26
426842 NM 004210 Hs.172700 πeurall∑ed (Drosophlla)-llke 2.26
442620 C00~138 Hs.8535 Homo sapiens mRNA for KIAA1668 protein, 2.25
409435 AI810721 Hs.95424 ESTs 2.25
418399 AF131781 Hs.84753 hypothetical protein FLJ12442 2.25
411006 AW813193 Hs.17767 KIAA1554 protein 2.25
418329 AW247430 Hs.84152 cystathlonlne-beta-synthase 2.25
429056 AW138568 Hs.104965 ESTs 2.25
406840 AW161940 Hs.2186 eukaryotlc translation elongation factor 2.25
410553 AW016824 Hs.272068 hypothetical protein MGC14128 2.25
421502 AF111856 Hs.105039 solute earner family 34 (sodium phospha 2.25
430937 X53463 Hs.2704 glutathlone peroxidase 2 (gastrolntestln 2.24
457485 AW081072 Hs.115960 KIAA0939 protein 2.24
432241 AI937060 Hs.6298 KIAA1151 protein 2.24
438821 AA826425 Hs.192375 ESTs 2.24
453863 X02544 Hs.572 orosomucoid 1 2.23
434844 AF157116 Hs.22350 hypothetical protein LOC56757 2.23
414075 U11862 Hs.75741 amlloride binding protein 1 (amine oxlda 2.23
417515 L24203 Hs.82237 ataxla-telanglectasla group D-assoclated 2.22
407792 AI077715 Hs.39384 putative secreted ligand homologous to f 2.22
430569 AF241254 Hs.178098 aπglotensin I converting enzyme (peptldy 2.22
449842 AA256233 Hs.112529 ESTs 2.21
436877 AA931484 Hs.121255 ESTs, Weakly similar to T21069 hypotheti 2.21
421267 BE314724 Hs.103081 ribosomal protein S6 kinase, 70kD, polyp 2.21
448571 AA486794 Hs.66915 ESTs, Weakly similarto 16.7Kd protein [ 2.21
408393 AW015318 Hs.23165 ESTs 2.21
425883 AL137708 Hs.161031 Homo sapiens mRNA; cDNA DKFZp434K0322 (f 2.21
406919 M88359 gb:Homo sapiens DNA-blndlπg protein (ZNF 2.21
411261 AW834655 gb:MR2-TT0014-291199-017-g11 TT0014 Homo 2.21
432941 W04803 Hs.279851 hypothetical protein FLJ10241 2.21
436409 AJ238982 Hs.183656 VNN3 protein 2.20
444081 AW593028 Hs.175939 ESTs 2.20
447472 AW207347 Hs.211101 ESTs 2.20
JARI.E 3B
Pkey: Unique Eos probeset identfler number
CAT number Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accession 428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 AI928140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658
AA769094 BF446026 AW118719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704
AI356361 AI923640 AW070509 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311
AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 BI061872 BI059498 AA134476
AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166
412560 72553.1 BF002870 AI003925 AI082639 AA194383 AA702993 AI767866 AL575096 BF593252 AI948584 AI678666 BI963722 AI765219 AA620965
BE671938 AI004689 AI004690 AI990303 AI127228 BE856290 AW203978 AI934786 AI770075 AI144132 AA812597 AI813349 AI142908
BE671242 AI208243 H82735 BF115200 AJ345984 BE044308 F32992 AJ346047 F24958 AJ346565 AJ346456 F18071 R24502 BI830577
BI222716 H83611 AA507760 BE463806AA194467AI865963 BF434962 C04894 AA813511 AA112966 N89963
447349 1063443 1 BE743847 AW809603 BM469626 AI375546
412383 1174261 1 AW947574 AW947732 AW947577 AW947576 AW947733 AW947734
406685 0 0 M18728
406835 0 0 A1318327 AI318328 AI318495
443845 507824 1 BG394808 BE858105 AI569728 AI590084 BE223011 AW007054 AI554692 AI939398 AW014243 AI088747 AI498970 AI199622 BF115458
BI714844 BI715424 AW135964 BG470892 BF347984 AI569769 AI424675 AI939616 BF116017 BF513472 AI828151 AI199676 AW139725
AI475044 AI128872 412452 71091.1 BE796667 BF330981 BE394193 Z45547 BG490525 F35734 AA130708 AA577072 AA446587 AA215665 AA978209 BG740729 BG746810
BE298184 AI356291 AI671975 AI818924 AV715722 AI078381 BI142391 AI201085 AI198283 AI077572 AI694848 AW016425 BM456416
AI277223 AW771476 F26140 AA102778 AW025780 R44726 AA761079 AI581346 AI991909 BM005939 BE537999 BG469717 AA114156
BF437200 BE774942
414580 623093 1 BG333973 BE385437 BE408833 BE387650 431912 610.10 BI763666 BI517886 BI759051 AI688604 AI660552 BF588523 AW004785 AW295479 BF591117 BF002672 BF064073 AA594441 AI380340
AI700219 AI659950 AI688540 AW296326
454453 8582 4 BF313069 BE879305 AW752781 AW752727 AW752559 AW752578 AW752584 BF846118 AL545903 BF846115 AL525361 437026 1240260.1 AW976573 AA742335 AA830000 444590 8582.1 BE907414 BI0849O2 AA907921 AI567715 AA653738 AA047537 AI554180 A1183767 AW440532 AI806052 AI148988 AA595689 AM 85031
AI174482 AI674395 AA292091 AA868B33 AI675517 AA481678 BF431759 A1698771 BE833514 AI742767 BF109855 F36782 F35533
AU149106 AI914985 AI143516 AW022296 AW118286 AI041751 AI499755 AI198299 AA862671 AI358871 AA160379 AA481440 AI003599
F28806 AA449176 BE871427 AA457456 BF906432 AA722113 AA022499 BI252800 T64216 BE872273 AA579472 AA355128 AA373128
T64403 F37911
427486 684159.1 BF510715 BE673055 BE464111 AW590620 AI637939 AA404324 AW236441 AI650952 BF056796 AA974433 411261 1074276.1 AW834670 AW834476 AW834691 AW834604 AW834655 AW834623
TABLE 3C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank Identifier (GI) numbers. "Dunham I. et al." refers to tie publication enttled 'The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495. Strand: Indicates DNA strand from which exons were predicted. NLpositlon: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLpositlon
405452 7656638 Minus 93876-94275
401151 9438288 Plus 30848-31228
403364 8571785 Plus 120351-120465
406016 8272661 Plus 41341-41940
403246 7637831 Minus 143547-143654,143741-143900
403140 9230855 Plus 69761-69894,70628-70889
403669 7259739 Minus 86103-86267
405151 7107980 Minus 45826-46035
401590 9966320 Minus 33547-33649
404645 9796894 Minus 19384-20220
406102 9124026 Minus 242917-243390
405003 6957544 Minus 129031-130073
406175 7249177 Minus 31058-31165
400914 3779013 Plus 116586-116729,117860-117986
401612 7705041 Minus 100597-100830
402961 9453790 Plus 42966-43193,53444-53524
403828 9838214 Plus 31755-32148
402943 6456831 Plus 38467-39068
402160 8516165 Plus 166063-166354
402463 9796896 Minus 8818-8952
TABLE 4A About 350 genes downregulated In breast metastases to the brain relative to primary breast liimnrs
Pkey Unique Eos probeset identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentle of breast tumor Als divided by the 90th percentle of breast metastases to the brain Als, where the 15th percentle of all normal body tissue Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic add and protein sequences associated with table entry
Pkey ExAccn R1 SEQ ID NO(s)
418026 BE379727 Hs 83213 fatty add binding protein 4, adlpooyte 3420 27 428398 AI249368 Hs 98558 ESTs 2908 50 452426 AI904823 Hs 31297 duodenal cytochrome b 1950 78 441591 AF055992 Hs 183 Duffy blood group 1667 63105 447205 BE617015 Hs 11006 ESTs, Moderately similar to T17372 plasm 1636 75 407694 U77594 Hs 37682 retnolc acid receptor responder (tazaro 1521 9 87 447990 BE048821 Hs 20144 small inducible cytokine subfamily A (Cy 1500 76 442321 AF207664 Hs 8230 a dlsintegπn like and metalloprotease ( 1498 67 117 420202 AL036557 Hs 95910 putative lymphocyte G0/G1 switch gene 1447 32 416950 AL049798 Hs 80552 dβrmatopoπtin 1439 2494 447225 R62676 Hs 17820 Rho-associated, colled coll containing p 14 13 422109 S73265 Hs 1473 gastrin releasing peptide 1357 428411 AW291464 Hs 10338 ESTs 1345 450701 H39960 Hs 288467 hypothetical protein XP.098151 (leuclne 1279 450239 BE541781 Hs 24697 cytldine moπophosphate-N-acetylneuramiπl 1251 431089 BE041395 ESTs, Weakly similar to unknown protein 11 92 453655 AW960427 Hs 342874 transforming growth factor, beta recepto 11 87 424206 NM 003734 Hs 198241 amine oxldase, copper containing 3 (vase 11 82 443932 AW888222 Hs 9973 tensin 11 75 412810 M21574 Hs 74615 platelet-derived growth factor receptor, 11 35 422087 X58968 Hs 111301 matrix metalloprotelnase 2 (gelatlnase A 11 22 418058 AW161552 Hs 83381 guanine nucleotide binding protein 11 11 20 415274 AF001548 Hs 78344 myosln, heavy polypeptide 11, smooth mus 11 03 451583 AI653797 Hs 24133 ESTs 1088 452669 AA216363 Hs 262958 hypothetical protein DKFZp434B044 1054 413624 BE177019 Hs 75445 SPARC like 1 (mast9, hevln) 1042 442561 NM 013450 Hs 8383 bromodomaln adjacent to zinc finger doma 1020 431971 BE274907 Hs 77385 myosln, light polypeptide 6, alkali, smo 10 16 446808 AA703226 Hs 16193 Homo sapiens mRNA, cDNA DKFZp586B211 (fr 997 420105 AW015571 Hs 32244 ESTs, Weakly simllarto FMOD.HUMAN FIBRO 997 408741 M73720 HS 646 carboxypeptdase A3 (mast cell) 977 428046 AW812795 Hs 337534 ESTs, Moderately similar to I38022 hypot 975 453299 W44626 Hs 30627 ESTs 958 453874 AW591783 Hs 36131 collagen, type XIV, alpha 1 (undulln) 955
M21305 FGENES predicted novel secreted protein 947
425701 AA361850 Hs 240443 Human clone 137308 mRNA, partial eds 935 417365 D50683 Hs 82028 transforming growth factor, beta recepto 902 408491 A1088063 Hs 7882 ESTs 901 414496 W73853 ESTs 893 415550 L13720 Hs 78501 growth arrest specific 6 891 421823 N40850 Hs 28625 ESTs 882 424634 NM 003613 Hs 151407 cartilage intermediate layer protein, nu 877 432485 N90866 Hs 276770 CDW52 antigen (CAMPATH-1 antigen) 876 422287 F16365 Hs 114346 cytochrome c oxldase subunlt Vila polype 866 416931 D45371 Hs 80485 adipose most abundant gene traπscπpt 1 865 442560 AA365042 Hs 325531 ESTs, Weakly similar to 2004399A chromos 858 406800 AA505535 gb nh84h10 s1 NCI_CGAP_Br1 1 Homo saplen 857 413856 D13639 Hs 75586 cyclln D2 855 456938 X52509 Hs 161640 tyrosine aminotransferase 853 447371 AA334274 Hs 18368 DKFZP564B0769 protein 842 453767 AB011792 Hs 35094 extracellular matπx protein 2, female o 834 437176 AW176909 Hs 42346 calclneurin binding protein calsarciπ 1 832 453676 AW853745 Hs 286035 hypothetical protein FLJ22686 8 32 414541 BE293116 Hs 76392 aldehyde dehydrogenase 1 family, member 804 453355 AW295374 Hs 31412 myopodln 791 413190 AA151802 Hs 40368 adaptor-related protein complex 1, slg a 787 446141 AW631255 Hs 324470 L-3 hydroxyacyl Coenzyme A dehydrogenase 777 421296 NM 002666 Hs 103253 perillpln 774 430410 AF099144 Hs 347933 tryptase beta 1 768 427373 AB007972 Hs 130760 myosln phosphatase, target subunlt 2 768 422550 BE297626 Hs 296049 mlcroflbrillar-assoclated protein 4 765 444933 NM 016245 Hs 12150 retinal short chain dehydrogenase/reduct 763 420255 NM 007289 Hs 1298 membrane metallo βndopeptdase (neutral 760 425B09 AA370362 Hs 57958 EGF-TM7-!atrophillπ related protein 751 449746 AI668594 Hs 176588 ESTs, Weakly simllarto CP4Y HUMAN CYTOC 748 436394 AA531187 Hs 126705 ESTs 748 448429 D17408 Hs 21223 calponln 1, basic, smooth muscle 746 427585 D31152 Hs 179729 collagen, type X, alpha 1 (Schmld metaph 737 406387 Target Exon 737 453180 N46243 Hs 110373 ESTs, Highly similar to T42626 secreted 736 454035 AW368993 Hs 323748 Homo sapiens clone CDABP0086 mRNA sequen 733 435684 NM 001290 Hs 4980 LIM domain binding 2 733 416157 NM 003243 Hs.342674 transforming growth factor, beta recepto 7.32
435359 T60843 Hs.189679 ESTs 7.31
452390 AI864142 Hs.29288 hypothetical protein FLJ21865 7.19
421124 AI366452 Hs.184430 ESTs 7.12
428834 AW899713 Hs.339315 ESTs 7.09
425247 NM 005940 Hs.155324 matrix metalloprotelnase 11 (stromelysin 7.08
417696 BE241624 Hs.82401 CD69 antigen (p60, early T-cell activatl 6.92
409038 T97490 Hs.50002 small Inducible cytokine subfamily A (Cy 6.87
456373 BE247706 Hs.89751 membrane-spanning 4-domaIπs, subfamily A 6.85
411962 AAO99050 gb:zk85d12. SoaresjregnaπLutems.NbH 6.85
418336 BE179882 glutathlone peroxidase 3 (plasma) 6.85
435010 N89307 Hs.124696 oxldoreductase UCPA 6.83
442895 AI814663 Hs.170133 forkhead box 01 A (rhabdomyosarcoma) 6.80
418283 S79895 Hs.83942 cathepsln (pycπodysostosls) 6.74
431493 AI791493 Hs.129873 ESTs, novel cytochrome P450 6.73
434096 AW662958 Hs.75825 plelomorphle adenoma gene-like 1 6.72
452093 AA447453 Hs.27860 Homo sapiens mRNA; cDNA DKFZp586M0723 (f 6.62
423366 Z80345 Hs.127610 acyl-Coenzyme A dehydrogenase, C-2 to C- 6.61
443679 AK001810 Hs.9670 hypothetlcal protein FLJ10948 6.58
436293 AI601188 Hs.120910 ESTs 6.50
423575 C18863 Hs.163443 Intron of periostin (OSF-2os) 6.49
411764 T40064 Hs.71968 Homo sapiens mRNA; cDNA DKFZp564F053 (fr 6.47
426488 X03350 Hs.4 alcohol dehydrogenase 1B (class I), beta 6.45
412088 AI689496 Hs.108932 ESTs 6.44
435088 NM 000481 Hs.102 amlnomelhyltransferase (glyclπe cleavage 6.37
408988 AL119844 Hs.49476 Homo sapiens clone TUA8 Cri-du-chat regl 6.35
430280 AA361258 Hs.237868 Interleukin 7 receptor 6.28
418310 AA814100 Hs.86693 ESTs 6.27
452307 R87866 Hs.95120 ESTs, Weakly simllarto HZHU hemoglobin 6.25
406801 AW242054 Hs.190813 ribosomal protein L9 6.25
456898 NM 001928 Hs.155597 D component of complement (adlpsln) 6.23
410611 AW954134 Hs.20924 KIAA1628 protein 6.22
453510 AI699482 Hs.42151 ESTs 6.19
450954 AI904740 Hs.25691 receptor (calcitonln) activity modifying 6.18
407828 AW959500 Hs.49597 retinolc add Induced 2 6.10
419047 AW952771 Hs.90043 ESTs 6.10
414005 AA134489 ESTs 6.04
418318 U47732 Hs.84072 transmembrane 4 superfamily member 3 6.01
421893 NM 001078 Hs.109225 vascular cell adhesion molecule 1 6.00
418994 AA296520 Hs.89546 selectin E (endothelial adhesion molecul 5.99
413956 AI821351 Hs.193133 ESTs, Weakly similar to ALU7 HUMAN ALU S 5.95
416030 H15261 Hs.21948 ESTs 5.93
424580 AA446539 Hs.339024 ESTs, Weakly similar to A46010 X-llπked 5.89
429697 AW296451 Hs.24605 ESTs 5.88
445457 AF168793 Hs.12743 camitiπe O-octanoyltransferase 5.86
437027 AB023235 Hs.5400 KIAA1018 protein 5.85
439569 AW602166 Hs.222399 CEGP1 protein 5.83
423024 AA593731 Hs.325823 ESTs, Moderately similar to ALU5.HUMAN A 5.82
438564 AA381553 Hs.198253 major hlstocompatlblllty complex, class 5.82
427605 NM 000997 Hs.337445 ribosomal protein L37 5.78
410023 AB017169 Hs.57929 silt (Drosophila) homolog 3 5.77
410016 AA297977 Hs.57907 small Inducible cytokine subfamily A (Cy 5.68
418807 NM 004944 Hs.88646 deoxyribonuclease l-like 3 5.63
436686 AW450205 Hs.305890 BCL2-llke 1 5.59
411988 AA455459 Hs.164480 ESTs, Weakly similar to T50609 hypotheti 5.59
407891 AA486620 Hs.41135 endomucln-2 5.57
418658 AW874263 Hs.32468 ESTs 5.57
427007 NM 006283 Hs.173159 transforming, acidic colled-coil contain 5.50
442441 AI820662 Hs.129598 ESTs 5.47
439310 AF086120 Hs.102793 ESTs 5.47
410066 AL117664 Hs.58419 DKFZP586L2024 protein 5.46
448121 AL045714 Hs.128653 hypothetical protein DKFZp564F013 5.45
441499 AW298235 Hs.101689 ESTs 5.43
459297 BE300741 Hs.125034 hypothetical protein FLJ13340 5.41
414807 AI738616 Hs.77348 hydroxyprostaglandln dehydrogenase 15-(N 5.40
409079 W87707 Hs.82065 Interleukin 6 signal transducer (gp130, 5.39
408339 R97502 Hs.30443 sentrin/SUMO-speclflc protease 5.39
440538 W76332 Hs.79107 mltogen-activated protein kinase 14 5.38
414449 AA557660 Hs.76152 decorin 5.35
452165 R17489 Hs.28264 Homo sapiens mRNA; cDNA DKFZp564L0822 (f 5.32
447073 AW204821 Hs.157726 ESTs 5.32
409981 AW516695 Hs.8438 ESTs 5.29
415385 R17798 Intron of COBW-like protein (NM.018491) 5.28
417788 AI436699 Hs.84928 nuclear transcripOon factor Y, beta 5.27
455863 AA907305 Hs.36475 ESTs 5.27
414522 AW518944 Hs.76325 Immunoglobulin J chain 5.25
457994 AW136239 Hs.132922 ESTs, Weakly similar to TI47 HUMAN CARGO 5.22
422994 AW891802 Hs.296276 ESTs 5.22
420570 AI453665 Hs.290870 ESTs, Weakly similar to I3B588 reverse t 5.21
431615 AW295859 Hs.235860 ESTs 5.21
419055 AI365384 Hs.11571 Homo sapiens cDNA FLJ11570 fis, clone HE 5.18
451820 AW058357 Hs.199248 ESTs 5.17
422583 AA410506 Hs.27973 KIAA0874 protein 5.17
421932 W51778 Hs.323949 kaπgal 1 (suppression of tumorigeπlclly 5.15
425095 AW014160 Hs.182585 KIAA1276 protein 5.14
419490 NM 006144 Hs.90708 granzyme A (granzyme 1, cytotoxic T-lymp 5.14 426406 AI742501 Hs.169756 complement component 1 , s subcomponent 5.12
418452 BE379749 Hs.85201 C-type (calcium dependent, carbohydrate- 5.11
437773 U24186 Hs.283018 replication protein A complex 34 kd subu 5.10
439177 AW820275 Hs.76611 ESTs, Weakly simllarto I38022 hypotheti 5.10
441233 AA972965 ESTs 5.08
428024 Z29067 Hs.2236 NIMA (never in mitosis gene a)-related k 5.06
416585 X54162 Hs.79386 leiomodln 1, smooth muscle (LMOD1) (Thy 5.03
459587 AA031956 gb:zk15e04.s1 Soares_pregnaπLuteπJS_NbH 5.03
410209 AI583661 Hs.60548 hypothetical protein PR01635 5.02
440874 NM 003188 Hs.7510 mltogen-actlvated protein kinase kinase 5.02
442070 BE244622 Hs.8084 hypothetical protein dJ465N24.2.1 5.01
408731 R85652 Homo sapiens mRNA; cDNA DKFZp434F1928 (f 5.00
420556 AA27830O Hs.124292 Homo sapiens cDNA; FLJ23123 fis, clone L 5.00
413200 AA127395 Hs.222414 ESTs 4.99
448141 AI471598 ESTs 4.99
414142 AW368397 Hs.334485 hemicentn (fibulin 6) 4.98
422241 YOO062 Hs.170121 protein tyrosine phosphatase, receptor t 4.98
452683 AI089575 progesterone membrane binding protein 4.98
421998 R74441 poly(A)-blndlng protein, nuclear 1 4.96
451287 AK002158 Hs.26194 likely homolog of mouse immunlty-assocla 4.95
451240 AJ131693 Hs.58103 A kinase (PRKA) anchor protein (yotlao) 4.94
427620 NM 003705 Hs.179866 solute carrier family 25 (mitochondrial 4.93
443514 BE464288 Hs.141937 ESTs 4.92
425498 . AL096725 Hs.289010 DKFZP434B103 protein 4.89
447571 AF274863 Hs.18889 DKFZP434M183 protein 4.88
452040 AW973242 Hs.293690 ESTs, Weakly simllarto I38022 hypotheti 4.88
432606 NM 002104 Hs.3066 granzyme K (serlne protease, granzyme 3; 4.88
422195 AB007903 Hs.113082 KIAA0443 gene product 4.87
450293 N36754 Hs.171118 hypothetical protein FU00026 4.85
446161 AA628206 Hs.14125 p53 regulated PA26 nuclear protein 4.83
442804 AW300118 Hs.131257 ESTs 4.83
414061 NM 000699 Hs.335493 amylase, alpha 2A; pancreatic 4.81
426310 NM 000909 Hs.169266 neuropeptide Y receptor Y1 4.80
420286 AI796395 Hs.111377 ESTs 4.80
434025 AF114264 Hs.216381 Homo sapiens clone HH409 unknown mRNA 4.79
436648 R18656 ESTs 4.78
449925 AI342493 Hs.24192 Homo sapiens cDNA FLJ20767 fis, clone CO 4.78
435573 AI580377 Hs.34656 ESTs 4.77
400419 AF084545 Target 4.77
419086 NM 000216 Hs.89591 Kallmaππ syndrome 1 sequence 4.77
422867 L32137 Hs.1584 cartilage oligomeric matrix protein (pse 4.76
431704 NM 006680 Hs.2838 malic enzyme 3, NADP()-depeπdent, mltoch 4.75
452107 AB020681 Hs.27973 KIAA0874 protein 4.74
427544 AI767152 Hs.181400 ESTs, Weakly simllarto I78885 serine/th 4.72
453143 AA382234 protein tyrosine phosphatase, receptor t 4.71
456676 AI870001 Hs.334479 ESTs, Moderately similar to KIAA1139 pro 4.71
442295 AI827248 Hs.224398 Homo sapiens cDNA FLJ11469 fis, clone HE 4.70
444483 AV649942 gb:AV649942 GLC Homo sapiens cDNA clone 4.69
430234 N29317 KIAA1238 protein 4.69
407183 AA358015 gb:EST66864 Fetal lung III Homo sapiens 4.68
438264 T86773 Hs.6133 calpaln 5 4.68
446564 AB037828 Hs.15370 KIAA1407 protein 4.68
401274 Target Exon 4.68
428804 AK0OO713 Hs.193736 hypothetical protein FLJ20706 4.65
437952 D63209 Hs.5944 solute carrierfamlly 11 (proton-coupled 4.65
424896 Z98520 Hs.274370 hypothetical protein FLJ20260 4.65
422092 AB007883 Hs.111373 KIAA0423 protein 4.64
451871 AI821005 Hs.118599 ESTs 4.64
414646 AA353776 Hs.901 CD48 antigen (B-cell membrane protein) 4.64
417640 D30857 Hs.82353 protein C receptor, endothelial (EPCR) 4.63
434975 AA657884 Hs.314413 ESTs 4.63
445263 H57646 Hs.42586 KIAA1560 protein 4.62
417339 AI912592 Hs.7882 ESTs 4.62
426992 BE244961 Hs.343200 FE65-LIKE 2 4.60
413489 BE144228 gb:MR0-HTO165-140200-009-d04 HT0165 Homo 4.60
447391 AI377444 Hs.54245 ESTs, Weakly similar to S65824 reverse t 4.60
412802 U41518 Hs.74602 aquaporlπ 1 (channel-forming Integral pr 4.60
451529 AI917901 Hs.208641 ESTs 4.59
443788 AI732643 Hs.144151 downstream of breast cancer antigen NY-B 4.57
429698 AI685086 Hs.26339 ESTs, Weakly similar to S21348 probable 4.57
430770 AA765694 Hs.123296 ESTs 4.57
404517 Target Exon 4.56
444301 AK000136 Hs.10760 asporin (LRR class 1) 4.55
459247 N46243 Hs.110373 ESTs, Highly similar to T42626 secreted 4.55
407374 AA724738 Hs.131034 ESTs, Weakly similar to I78885 serine/th 4.55
446874 AW968304 Hs.56156 ESTs 4.55
447894 AW204253 Hs.21912 ESTs 4.54
437984 AA781435 Hs.334772 hypothetical protein FLJ13614 4.54
425106 AA398972 Hs.18987 Homo sapiens BAC clone RP11-505D17 from 4.54
433735 AA608955 Hs.109653 ESTs 4.53
438691 AA906288 ESTs 4.53
409062 AL15748B Hs.50150 Homo sapiens mRNA; cDNA DKFZp564B182 (tr 4.52
426128 NM.001471 Hs.167017 gamma-amlπobutyricacld (GABA) B recepto 4.52
407136 T64896 Hs.287420 Homo sapiens cDNA FLJ 11533 fis, clone HE 4.51
444331 AW193342 Hs.24144 ESTs 4.50
444213 T79623 Hs.263351 ESTs 4.49 412584 X54870 Hs.74085 DNA segment on chromosome 12 (unique) 24 4.49
411088 BE247593 Hs.145053 ESTs 4.49
414742 AW370946 Hs.23457 ESTs 4.48
441281 BE501247 Hs.144084 ESTs 4.47
407939 W05608 Hs.312679 ESTs, Weakly simllarto A49019 dyneln he 4.47
421255 BE326214 Hs.93813 ESTs 4.45
431725 X65724 Hs.2839 Norrie disease (pseudoglloma) 4.45
420311 AW445044 Hs.38207 Human DNA sequence from clone RP4-530I15 4.44
406687 M31126 matrix metalloprotelnase 11 (stromelysln 4.44
438150 AA037534 Hs.342874 transforming growth factor, beta recepto 4.41
413902 AU076743 Hs.75613 CD36 antigen (collagen type 1 receptor, 4.40
434666 AF151103 Hs.112259 T cell receptor gamma locus 4.40
436169 AA888311 Hs.17602 Homo sapiens cDNA FLJ12381 fis, clone MA 4.39
418007 M13509 Hs.83169 matrix metalloprotelnase 1 (Interstitial 4.39
452973 H88409 Hs.40527 ESTs 4.39
459501 AA854133 Hs.310462 ESTs 4.39
447109 X69086 Hs.286161 Homo sapiens cDNA FLJ13613 fis, clone PL 4.38
413869 NM 000878 Hs.75596 Interleukin 2 receptor, beta 4.37
440561 AA471379 Hs.7277 peroxlsomal biogenesis factor 3 4.36
428957 NM 003881 Hs.194679 WNT1 Inducible signaling pathway protein 4.35
420517 AB011115 Hs.98507 KIAA0543 protein 4.35
458627 AW088642 Hs.97984 SRY (sex determining region Y)-box 17 (S 4.35
411779 AA292811 Hs.72050 non-metastatic cells 5, protein expresse 4.35
431474 AL133990 Hs.190642 CEGP1 protein 4.34
416749 AW068550 Hs.79732 flbulln 1 4.34
418479 AA829976 mannosldase, alpha, class 1A, member 2 4.34
404262 ENSP00000211196:D J137F1.2 (novel member 4.33
426802 AA385182 Hs.46699 ESTs 4.33
408735 AI654450 Hs.281706 Homo sapiens mRNA; cDNA DKFZp564B176 (fr 4.33
428232 BE272452 Hs.183109 monoamlne oxldase A 4.32
418307 U70867 Hs.83974 solute carrierfamlly 21 (prostaglaπdin 4.31
422959 AV647015 paired immunoglobulln-like receptor beta 4.31
423778 Y09267 Hs.132821 flavin containing monooxygenase 2 4.31
402458 C1002064:gi|11993050|gb|AAG42574.1|AF144 4.31
431992 NM 002742 Hs.2891 protein kinase C, mu 4.31
415801 R24219 Hs.278443 Fc fragment of IgG, low affinity lib, re 4.31
422128 AW8B1145 gb:QV0-OT0033-010400-182-a07 OT0033 Homo 4.31
433793 AW975959 Hs.107513 ESTs, Moderately similar to KIAA1058 pro 4.31
438315 R56795 Hs.82419 ESTs 4.30
434365 AI073378 Hs.126793 ESTs 4.30
414033 AL079707 Hs.207443 hypothetical protein MGC10848 4.30
410387 AI277367 Hs.47094 ESTs 4.30
421712 AK000140 Hs.107139 hypothetical protein 4.29
424789 BE176694 Hs.279860 tumor protein, translationally-controlle 4.29
420931 AF044197 Hs.100431 small Inducible cytokine B subfamily (Cy 4.29
449203 AI634578 Hs.282121 ESTs 4.29
429165 AW009886 Hs.118258 prostate cancer associated protein 1 4.28
403845 NM_020666*:Homo sapiens protein seine t 4.28
412116 AW402166 Hs.784 Epsteln-Barr virus Induced gene 2 (lymph 4.28
444649 AW207523 ESTs 4.28
412745 AW994221 gb:RC3-BN0036-25O200-O12-dO9 BN0036 Homo 4.28
437644 AA748575 Hs.136748 leclin-like NK cell receptor 4.28
417317 AW296584 Hs.293782 ESTs 4.27
419169 AW851980 Hs.262346 ESTs, Weakly similar to S72482 hypotheti 4.27
447742 AF113925 Hs.19405 caspase recruitment domain 4 4.26
407758 D50915 Hs.38365 KIAA0125 gene product 4.26
431955 AL133606 Hs.272244 hypothetical protein FLJ11142 4.26
407307 H73271 gb:yu04d05.r1 Soares fetal liver spleen 4.25
452235 AL039743 Hs.28514 testes development-related NYD-SP21 4.24
408380 AF123050 Hs.44532 dlublquitln 4.24
407826 AA128423 Hs.40300 calpalπ 3, (p94) 4.24
422431 AI769410 Hs.221461 ESTs 4.23
433972 AI878910 Hs.278670 cisplatln resistance-associated overexpr 4.23
454338 AW381251 gb:RC0-HT0297-301099-011-aOB HT0297 Homo 4.23
424377 AF081675 Hs.146322 killer cell lectin-llke receptor subfaml 4.22
412220 BE350058 Hs.36787 chromodomaln hellcase DNA binding protel 4.22
407277 AW170035 Hs.326736 Homo sapiens breast cancer antgen NY-BR 4.21
421362 AK000050 Hs.103853 hypothetical protein FLJ20043 4.21
415054 AI733907 gb:zo86h09.y5 Stratagene ovarian cancer 4.21
427326 AI287878 gb:qv23I06.x1 NCI_CGAP_Lym6 Homo sapiens 4.21
447241 BE382838 Hs.19322 Homo sapiens, Similar to RIKEN cDNA 2010 4.21
416370 N90470 Hs.203697 CD38 antigen (p45) 4.19
417437 U52682 Hs.82132 Inlerferon regulatory factor 4 4.19
424243 AI949359 Hs.143600 ESTs, Highly similar to els Golgl-locali 4.18
437275 AW976035 Hs.292396 ESTs, Weakly simllarto A47582 B-cell gr 4.17
425367 BE271188 Hs.155975 protein tyrosine phosphatase, receptort 4.17
411878 AW873296 Hs.273742 ESTs 4.17
446170 H49664 Hs.125790 leuclne-rich repeat-containing 2 4.17
451872 AI821008 Hs.10697 ESTs 4.17
400143 Eos Control 4.16
420914 AA281697 Hs.334827 gb:zl03d10.r1 NCI.CGAP.GCBI Homo sapiens 4.16
417054 AF017060 aldehyde oxldase 1 4.15
423837 AW937063 Hs.275150 gb:PM3-DT0037-231299-001-g11 DT0037 Homo 4.15
433855 AA834082 Hs.307559 ESTs 4.15
420061 AW024937 Hs.29410 ESTs 4.15
429490 AI971131 Hs.23889 ESTs, Weakly simllarto ALU7 HUMAN ALU S 4.15 422226 AW517457 Hs.42390 nasopharyngeal carcinoma susceptibility 4.14 401586 Target Exon 4.13 414152 NM 003248 Hs.75774 thrombospondin 4 4.12 419005 T86358 Hs.193931 ESTs, Weakly simllarto I54374 gene NF2 4.12 410088 AA73B034 gb:πx15e08.s1 NCI CGAP.GC3 Homo sapiens 4.12 453876 AW021748 Hs.110406 ESTs, Weakly similar to I38022 hypotheti 4.12 436283 A1480319 Hs.120058 ESTs 4.12 439673 T53169 Hs.9587 Homo sapiens cDNA: FLJ22290 fis, clone H 4.12 443622 AI911527 Hs.11805 ESTs 4.12 448490 AI523897 Hs.271692 ESTs, Weakly simllarto I38022 hypotheϋ 4.12 417355 D13168 Hs.82002 endothelln receptor type B 4.11 408776 AA057365 ESTs, Weakly simllarto I38022 hypotheti 4.11 408180 N98311 gb:yy68e04. Soares.multiple.sclerosls. 4.11 404917 Target Exon 4.11 453216 AL137566 Hs.32405 progesterone receptor (PR) 4.10 431708 AI698136 Hs.108873 ESTs 4.10 420224 M84371 Hs.96023 CD19 antigen 4.10 426486 BE178285 Hs.170056 Homo sapiens mRNA; cDNA DKFZp586B0220 (f 4.10 428594 BE387236 Hs.75415 beta-2-microglobulin 4.10 424874 AA347951 Homo sapiens cDNA FLJ20812 fis, clone AD 4.09
TAB1 F 4R Pkey: Unique Eos probeset Identifier number
CAT number. Gene cluster number
Accession: Genbank accession numbers Pkey CAT number Accession
431089 125941.2 BG940189 AW063489 AA715980 BF001091 BF880066 AA666102 AA621946 AA491826 414496 1526.1 AK058006 BF724822 W65303 AW887764 AW023806 Z25353 AW022095 AA730973 W00417 W73819 BF982096 AI927669 AW188021
AW770478 AI913512 AA604358 AI697341 AI691028 AI338392 AI079403 H97538 AI144448 AI253102 AI051402 AI335900 AI868132
N28900 H98465 AF268386 AI799915 AI819228 BE048413 AW304723 AI819923 BF223106 AA155907 AW298079 BF055272 BF446804
BF197697 W58588 BF197538 AA032180 AA992597 AW590254 AA027824 AI129369 AI131331 AI655843 AA932907 AW104493 AI150615
BF110226 AW172271 AI312659 AA057312 BE673669 AA722984 AW104985 AI129232 AI078648 AI653086 AI703481 AW515897 AI352206
N67076 AW297281 AI686162 AA029184 AI610743 AW772016 AI091778 W65401 AI687374 AI218085 AI765158 AI018002 AI653068
AI335704 AI520850 AW275228 AW275204 AI420247 AA975336 AI697042 AW182235 AA736386 AI281682 AW169698 AW263325
BE645834 AI377438 AI146706 AA613808 AA716538 BI496247 AA032248 AI698930 AI193399 N70026 H86792 AA404489 W61267
BF447230 AA910805 AA150774 AA621907 AA902526 AI827634 AW022037 BF059000 BI496246 BG577007 BG571077 AA460779
AW816890 AW816893 AW816891 AA029183 AA010295 H86850 T83320 BE160823 H12925 N40087 AA096372 BE160847 AW816892
AW816889 AW816882 AW816868 AW816941 AW816578 AW816940 AW816577 AI431628 AI828113 AA033677 AA033654 AA452704
AA317582 AA346971 BF836584 H48669 BI861605 BG925200 AA463277 H89048 AA155952 W03252 W01510 W00915 W58589 AA164519
N24017 N24622 N27149 N70109 R43771 AA010296 W84611 H98889 H88965 AW594424 AA034139 AA065223 N99696 BG981481 N94371
AA767970 W47146 N70977 H05510 W61268 T90796 AA164518 W47244 AA150883 AA034138 BF338483 F13671 H51317 W72716 N21488
AI188071 AI370541 AI754442AA148524 AI749182W95221 W92522 R20385
406800 0.0 AA505535 411962 2307710.1 AA099050 AA099526 T47733 418336 58817.1 AW969583 BI772505 BE179578 AI493714 AI937718 AA663709 BI868925 AW138743 AI911314 BE645538 BG911947 AI380325 AI265803
W56175 AI658779 AI675997 AW665991 AI459263 AI420121 Z38874 AA570115 AW301008 AA216257 BF062662 BI772789 H05989
BF085523 BI001277
414005 259333 1 AW968220 AA259126 AA287352 AA279767 AI479143 AA863044 AA134489 H49266 L32048 415385 285.10 N92510 AW058040 AW027717 H26334 BG619539 BG426083 Z46181 F07399 R17798 AI861887 AA419558 AU185438 BE926285
AA382353
441233 2645856 ' AA972965 AI685347 AA923446
459587 93128.1 BG545629AA031999 AA031956 408731 11725.2 AF305826 BE350971 AI765355 AW172600 AI310231 BM271766 AI547292 AW612019 AI674617 AW138666 AI147629 AI147620 BF857810
BF886300 BF885952 BF886303 BF885956 BG565497 BE670834 AA114025 BF886396 BF886928 AV750861 D62864
448141 2047395 1 A1660692 AI471598 H96927 452683 47038.2 BG939450 AA775472 AW058592 BE855643 BF055005 AA864765 AI278037 AI655048 AI201557 AI687448 AI143618 BE500960 W58669
AI659870 A1089575 AI668821 AA709020 AI978936 AI338511 AA600231 AI086687 AI090569 AI146299 BF221488 AI250850 AA663309
AA744980 AA968965 AI088224 AI474516 AW057610 BE858855 AI624190 AI161307 AI247088 AA126444 AA126743 AI125007 AI433915
AI708238 AA663513 AI370250 AA027291 AI763349 AA454524 AI708805 AA126568 AW089710 W58670 AI202620 BE835776 AW197418
AA126821 AI961169 BG152992 F37518 BF907190 AI932429 AI421633 AI419518 W19340 BI818890 H89569 H89568 AA057704 BG028664
BG741413 AW803665 AW889928 BF378811 BF088437 AA027290 BF093514 AW959502 AA456193 AA330467 R19974 R21000 AA362856
W25522
421998 133592.1 BI757233 BG911321 BF351759 AW244016 AW026834 AW024260 AI420138 AA779354 AI093360 AI934858 AW151292 AI373133 AI335587
AI969728 AA101632 BE218525 AI802114 AI783721 AA845265 AW088826 AI832852 F03967 AI611148 AI720358 AW293764 N91161
R79192 W85852 AW771263 BG820263 BG012864 R74441 R86080 W04256 BE707244 BF899452 BE327552 BE669500 AI492388
AI241532 BF448184 AI209012 AA886528 N70309 AW582776 BF110563 BF448329 BE326537 AW770471 BF444926 BE674147 AI793266
AI991774 AI807726 AI218667 AA301750 R44328
436648 52977.1 AJ002788 AL118666 AI381600 BE672862 AW500520 BF223709 AW593740 AA262174 AA810597 AA810596 AA810595 F09382 BF976590
AW968002 AA262288 BF931698 AW968014 R18656 BM459356 AW794189 BF954184 Z42558 BF891641 BF963380 Z45874 F05187
X93079 BF742651 BF742649 R51324 DB0031 BI457883 F06613 Z43128 F12243 BF950830 H19040 BF950829 F06439 R14947 F06702
R61037 R52173 R14953 R12174 R13610 H10426 R11851 T65264 R18737
453143 10116.6 BG542081 BF793365 AI371013 AI147536 AW005418 AA416767 AI083516 AI698032 AA410929 AI936116 AI079893 AA747741 BF940413
BM007681 F12285 N75819 AI971415 AA032249 AW867908 AWB67914 AI520867 BG990651 AA570507 AA036654 AA063585 AA873147
AI538117 AA382234 T66232 BE272411 AA834031 BG122734 BI769788 W55850 AW879266
444483 389121.1 AV649942 AV719783 AV650843 AV720464 430234 1746.1 AW025803 AL137567 AI760919 BE552289 AW082686 AA913951 BE501313 AV756373 BE048863 AA828185 BG151502 AI655583
AW473377 AI949888 AA453495 AW130287 AI222766 AI862122 AI3092B8 AL038626 AA714749 AI719007 W95486 N29317 AW589706
AA905486 AI744057 AA759318 AI084950 AI273294 BF835579 AW235310 AI914478 BF887920 R21864 AI479541 AW189671 AW235752
AI762157 BG698714 AA461269 AA460813 W95524 AA301369 AI760649 BF854009 AW303856 H42B31 AV737305 H03702 R22396 R65961
413489 1517623.1 BE144228 BE144291 438691 2575806.1 AA829941 AA906288 AI914939 AA814353 406687 0.0 M31126 418479 175360.1 BFS66791 BG564455 BE672212 AI151416 AI566231 AI417585 AI378391 AA236264 AI337574 AI346166 AA406590 AA748618 AW771957
AA478626 AW338072 AI889444 AI810315 BE503662 BG231886 AI888230 AI289102 BF594638 AW074094 AW512456 AA832229
AI056108 AI025868 AI245806 D61957 AI093841 AI721013 AI597594 AA993022 AH 28620 AI285106 W37459 W35410 N90037 AA890323
R39943 AI468741 AA829976 AA479201 AI539018 AA875875 AA448827 AW779493 Z39056 H84925 AA223923 AW517592 AI804400
AA911882 BM353143 D62885 AI457883 AI880626 R31694 R42772 R68804 R44147 R71463 AV742540 BF966987
422959 MH905.3 AJ400845 AI954159 AL041618 AI028269 AA769325 AW780241 AW129462 AI271476 BF798303 AA836991 AW273346 AI436321 AI375545
AL040967 AA889495 AI922524 AA598667 AA423804 AL040910 N80292 AI954063 AI923968 AI400578 AA748499 BE677845 AW020788
AA860230 AW519209 AA767391 AI860419 AA476935 AW452389 AI017695 AA806940 BI497005 AI051533 AI650706 AI811516 AA609569
AI43919B BF430946 AA749268 AI624860 AI784422 BI491753 AI206880 BE671796 AI431957 AI187038 AI678429 AI273421 AA897667
AA586499 BE241923 AF161081 NM.013440 BE073169 AI700673 AV699081 AV684786 AV688081 AV689220 AV689216 AA132636
BF086186 BF917106 AV762653 BI064033 BE168145 AA778650 AI984255 W69468 AA132452 N53166 AI949278 AW168519 F28686
AA908333 F37181 BI002729
422128 1751616 BI261864 BI036453 BI023096 BI023388 AA331991 AV721898 AW881145 AA490718 M85637 T06067 AV761102 BI023091 BI022906
444649 6300741 AI184631 AW138226 AI917315 AI825123 AI651395 AI636782 AI990399 AW207523
412745 1246023.1 AW994221 AW994211 BE075786 AW994378
407307 19842871 H73271 R96266 H73959 R96214
454338 788429 -2 AW381251
415054 30707321 AI732614 AA 159708 AI733907
427326 565.21 Y10529 BF062364 BE501015 AA758739 AF359418 AF359419 BM021254 AF359416 BI087915 BG995764 BF345274 BG431056 AI804160
AI287878AA400787
400143 11259.1 BC004324 NM.001020 BC007977 M60854 BM050628 BG829809 BE385504 BG744451 BI826914 BE440007 BI260656 BE395117
BE389334 BE255792 BI194169 BI668218 BI194376 BG716213 BG714408 BE392513 AV722219 AW328077 BM424171 BI828267
AW958606 BG831252 BE392943 BE394033 BI858915 BI668334 BE621019 BG706995 BE791985 BF967484 BI193635 BG761859
BM466537 BG747165 BG827488 AI133550 BM011511 BI227282 BG489212 BG478388 BE727789 BI160880 BG831707 BG324692
BM470427 BI083889 BG831605 BG754114 BG420536 BF308210 BE384213 BG832271 BG828032 BG481641 BF205675 BE899041
BE271558 BI193807 BI159866 BG473786 BG397178 BI194428 BI117210 BG768326 BG759507 BF975645 BF343657 BM020598
BG831082 BG829943 BG829501 BF306557 BE562511 BM050145 BM017978 BI193934 BI160764 BI160371 BG754991 BF973348
BF663234 BF032537 BE388168 BM009051 BI192794 BG831002 BG830459 BG764737 BG761808 BG481705 BG104314 BM464565
BI261500 BG831857 BG831684 BG829852 BG765030 BG760419 BG760268 BG749762 BG480900 BG419627 BG248771 BF975542
BM042233 BI161149 BG831302 BG830033 BG829626 BM050064 BI193014 BI161360 BG822729 BG110091 BG106500 BI258369
BG831982 BM458301 BM019513 BI161350 BI114178 BG481969 BG474870 BF974048 BF971122 BE741405 BE395269 BG832027
BG831469 BG490895 BM413638 BG943529 BG831012 BG829471 BG686284 BG337575 BG336551 BF206677 BI258301 BI160946
BG105893 BF183072 BM459542 BI193881 BG832043 BG831323 BI194545 BI160968 BG755930 BG706018 BE743865 BM465145
BG831227 BG774290 BF683451 BE907161 BM045391 B1194396 BI161269 BG747091 BG546643 BF984863 BM60206 BI226402 BI226336
AW328236 BG339458 BF972634 BE909808 BI160988 BI160251 BG828764 BG826860 BG758360 BF568228 BI818282 BI457127
BG831491 BG759864 AI830010 BF568381 BE907238 BI161172 BI116773 BG827153 BG825088 BG335419 BG109404 AI929068
BE906354 BE408564 BM045O0O BG339617 BG282794 BG335767 BE907263 BF568921 BG829961 BG479305 BG260397 AI922228
BE301975 AW516055 BG480919 BG480626 AW196817 BG336261 BE906157 BE395717 BE391427 BI192954 BG829757 BG476379
BE301536 BE394727 BE257695 BE905344 AI433577 BE894416 BE886992 BE409223 BF034756 BE904077 BG830886 BE909153
BE907998 BE395767 A1871751 BE744523 BI192663 BG831669 AI000225 BE743836 BE272515 AA628078 BM463802 BE393375
BE393033 AW170187 BE730961 BE395410 BE744572 BE392297 BE391448 BE390780 BE388821 BE258477 BE905970 BE901567
BE898833 BE880326 BF726889 BE910504 BE390753 BE390131 AA650542 BE744156 BE394125 BE742207 BE395265 BE392942
BE894336 BE378222 BE906926 BE904650 BE393704 BE620999 BE515162 BE378753 BE272370 BE907458 BE612801 BE392484
BE907636 BE907353 BE910491 BE909796 BE905331 AW248173 AI683576 BE908826 BE620180 BF037570 BE908312 BE615015
BE256977 BE746875 BE394133 BE391478 BE910068 BE907185 BE742109 AA995746 BE561195 BE908825 BE906472 BE906509
BE906017 BE910442 BE514657 BI261969 BE741707 BE392216 BM042793 BF570283 BI262119 BE395707 BE378298 AW327827
BE394422 BF569178 BE263240 AI700512 BG830290 BF569308 BF569156 BI194587 BE390831 BG745096 AI681675 BE395674 AA136372
BE279892 AA442822 BE384898 AA313519 AI878866 AA305904 F33366 BE394852 F29153 F33618 AI133637 AA300009 F34063 F29455
AU099691 AI905085 AI906656 AA343249 BE388691 AW404280 AA379888 F29022 BF089981 F31013 F24305
417054 12405.2 BG533564 BG618564 AW296119 AI269233 BF508328 AW364777 AW292258 AA371049 AI452471 AI092522 BG618376 AL049080
AA631068 BG564643 T53833 AV702544 BG533452 AV705004 AA588281 T28665 BG569026 AV646874 AV647253 AV647455 AV647749
BI759444 AV652457 AV695354 AV696010 AV697248 BG617586 AV722549 AI435836 AI590676 AI245019 AW338243 AA530898 D52191
AI435352 D57473 BG566952 AI420505 AA035245 AV704972 BG564113 AI439237 AI287456 AV695686 AA349017
410088 1241437 1 AW977844 AA738034 AA081561
408776 106302 1 BF057799 BE218747 T15720 AA057365 AI811370
408180 640212.1 N98311 BE160207AW168088
424874 11607.6 AI688463 BF959633 BF897027 AA883123
TABLE 4C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank Identiter (GI) numbers. "Dunham I. et al." refers to the publication entitled "The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495. Strand: Indicates DNA strand from which exons were predicted. NLpositlon: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLpositlon
406387 9256180 Plus 116229-116371,117512-117651
401274 8954206 Minus 111258-111378
404517 8151983 Minus 92340-92443
404262 9367893 Minus 69642-69807,70646-70812
402458 9796782 Plus 170479-171134
403845 9959258 Minus 87151-87288,87539-87633,88216-88382,8847
401586 9838242 Minus 93974-94099
404917 7341851 Plus 49330-49498 TABLE 5A: About 489 genes downregulated In hreast metastases to the brain relative to normal breast tssue
Pkey: Unique Eos probeset Identifier number
ExAccn: Exemplar Accession number, Genbank accession number
UniGenelD: UniGene number
UniGene Title: UniGene gene title
R1: goth percentile of normal breast tissue Als divided by the 90th percentile of breast metastases to the brain Als, where the 15th percentle of all normal body tissue Als was subtracted from the numerator and denominator.
SEQ ID NO(s): SEQ ID number's) for nucleic add and protein sequences associated with table entry.
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s):
418026 BE379727 Hs.83213 fatty acid binding protein 4, adipocyte 94.34 27
447205 BE617015 Hs.11006 ESTs, Moderately similar to T17372 plasm 75.45 75
420202 AL036557 Hs.95910 putatve lymphocyte G0/G1 switch gene 51.29 32
416950 AL049798 Hs.80552 dermatopontn 41.57 2494
410677 NM 003278 Hs.65424 tetranectln (plasmlnogen-blndlng protein 40.07 16 91
441591 AF055992 Hs.183 Duffy blood group 39.13 63 115
453655 AW960427 Hs.342874 transforming growth factor, beta recepto 35.85 80
426488 X03350 Hs.4 alcohol dehydrogenase 1B (class I), beta 31.80 47 105
443932 AW888222 Hs.9973 tensln 31.62 69
447990 BE048821 Hs.20144 small Inducible cytokine subfamily A (Cy 31.16 76
454059 NM.003154 Hs.37048 slatherin 30.14
415274 AF001548 Hs.78344 myosln, heavy polypeptide 11, smooth mus 30.07
416931 D45371 Hs.80485 adipose most abundant gene transcript 1 29.91
442321 AF207664 Hs.8230 a dislntegrln-llke and metalloprotease ( 29.18
414541 BE293116 Hs.76392 aldehyde dehydrogenase 1 family, member 28.50
424206 NM 003734 Hs.198241 amine oxldase, copper containing 3 (vase 28.07
421998 R74441 poly(A)-b!ndIng protein, nuclear 1 27.35
428232 BE272452 Hs.183109 monoamlne oxldase A 27.07
410635 D58863 Hs.347963 chorlonic somatomammotropln hormone 1 (p 26.61
418058 AW161552 Hs.83381 guanine nucleotide binding protein 11 25.80
416157 NM 003243 Hs.342874 transforming growth factor, beta recepto 25.08
443514 BE464288 Hs.141937 ESTs 24.80
411939 AI365585 Hs.146246 ESTs 24.50
445263 H57646 Hs.42586 KIAA1560 protein 23.85
422287 F16365 Hs.114346 cytochrome c oxldase subunlt Vila polype 23.37
412810 M21574 Hs.74615 platelet-derived growth factor receptor, 21.92
428398 AI249368 Hs.98558 ESTs 21.53
421296 NM.002666 Hs.103253 peπlipin 21.52
417365 D50683 Hs.82028 transforming growth factor, beta recepto 21.33
407694 U77594 Hs.37682 retinolc acid receptor responder (tazaro 20.91
412047 AA934589 Hs.49696 ESTs 20.20
411962 AA099050 gb:zk85d12.r1 Soares_pregnanLuterus_NbH 20.05
452426 AI904823 Hs.31297 duodenal cytochrome b 20.04
422550 BE297626 Hs.296049 microfibrillar-assoclated protein 4 19.29
435684 NM 001290 Hs.4980 UM domain binding 2 19.08
414496 W73853 ESTs 18.40
456898 NM.001928 Hs.155597 D component of complement (adlpsin) 18.38
412442 AI983730 Hs.26530 serum deprivation response (phosphat yl 18.35
423024 AA593731 Hs.325823 ESTs, Moderately similar to ALU5.HUMAN A 18.03
407744 AB020629 Hs.38095 ATP-blπdlng cassette, sub-family A (ABC1 17.87
430310 U60115 Hs.239069 four and a half UM domains 1 17.77
446808 AA703226 Hs.16193 Homo sapiens mRNA; cDNA DKFZp586B211 (fr 17,70
428848 NM.000230 Hs.194236 leptln (murine obesity homolog) 17.24
413624 BE177019 Hs.75445 SPARC-llke 1 (mast9, hevin) 16.55
453355 AW295374 Hs.31412 myopodln 16.33
453767 AB011792 Hs.35094 extracellular matrix protein 2, female o 16.15
423778 Y09267 Hs.132821 flavin containing monooxygenase 2 16.03
410023 AB017169 Hs.57929 silt (Drosophila) homolog 3 15.92
443060 D78874 Hs.8944 . procollagen C-endopeptldase enhancer 2 15.91
435088 NM.000481 Hs.102 aminomethyltransferase (glyclne cleavage 15.75
429350 AI754634 Hs.131987 ESTs 15.72
416585 X54162 Hs.79386 lelomodln l, smooth muscle (LMOD1) (Thy 15.28
446141 AW631255 Hs.324470 L-3-hydroxyacyl-Coenzyme A dehydrogenase 15.16
453676 AW853745 Hs.286035 hypothetical protein FLJ22686 15.13
442895 AI814663 Hs.170133 forkhead box 01 A (rhabdomyosarcoma) 15.02
443679 AK001810 Hs.9670 hypothetical protein FLJ10948 15.01
425809 AA370362 Hs.57958 EGF-TM7-Iatrophlliπ-related protein 15.00
427373 AB007972 Hs.130760 myosln phosphatase, target subunlt 2 14.95
407102 AA007629 glycerol-3-phosphate dehydrogenase 1 (so 14.94
451533 NM.004657 Hs.26530 serum deprivation response (phosphatdyl 14.94
420105 AW015571 Hs.32244 ESTs, Weakly simllarto FMOD HUMAN FIBRO 14.77
447371 AA334274 Hs.18368 DKFZP564B0769 protein 14.74
414290 AI568801 Hs.71721 ESTs 14.51
424098 AF077374 Hs.139322 small proline-rich protein 3 14.45
413902 AU076743 Hs.75613 CD36 antigen (collagen type I receptor, 14.33
417852 AJ250562 Hs.82749 transmembrane 4 superfamily member 2 14.30
431971 BE274907 Hs.77385 myosln, light polypeptide 6, alkali, smo 13.84
427007 NM.006283 Hs.173159 transforming, a dle colled-coil contain 13.83
420255 NM 007289 Hs.1298 membrane metallo-endopeptdase (neutral 13.76
447225 R62676 Hs.17820 Rho-assoclated, coiled-coll containing p 13.75
448429 D17408 Hs.21223 calponln 1, basic, smooth muscle 13.66
452123 AI267615 Hs.38022 ESTs 13.20 414033 AL079707 Hs.207443 hypothetical protein MGC10848 13.12
444933 NM.016245 Hs.12150 retnal short-chain dehydrogenase/reduct 13.07
454229 AW957744 Hs.278469 lacrimal praline rich protein 12.83
425280 U31519 Hs.1872 phosphoenolpyruvate carboxykiπase 1 (sol 12.72
422195 AB007903 Hs.113082 KIAA0443 gene product 12.58
403593 Target Exon 12.52
409882 AJ243191 Hs.56874 heat shock 27kD protein family, member 7 12.22
437275 AW976035 Hs.292396 ESTs, Weakly simllarto A47582 B-cell gr 12.03
406800 AA505535 gb:nh84h10.s1 NCI.CGAP.BrH Homo saplen 11.99
450239 BE541781 Hs.24697 cylidine monophosphate-N-acetylπeuramlnl 11.86
422087 X58968 Hs.111301 matrix metalloprotelnase 2 (gelatinase A 11.80
435010 N89307 Hs.124696 oxldoreductase UCPA 11.80
453874 AW591783 Hs.36131 collagen, type XIV, alpha 1 (undulin) 11.72
412295 AW088826 poly(A)-blndlπg protein, nuclear 1 11.67
427980 AA418305 Hs.303205 EST 11.65
441499 AW298235 Hs.101689 ESTs 11.60
446500 U78093 Hs.15154 sushi-repeat-contalnlng protein, X chram 11.49
453299 W44626 Hs.30627 ESTs 11.48
419271 N34901 Hs.238532 ESTs 11.40
416729 U46165 Hs.1027 Ras-related associated with diabetes 11.39
407570 Z19002 Hs.37096 zinc finger protein 145 (Kruppel-like, e 11.37
426928 AF037062 Hs.172914 retπol dehydrogenase 5 (11 -cis and 9-cl 11.35
433633 AI880516 Hs.84630 ESTs, Weakly simllarto 2004399A chromos 11.33
452669 AA216363 Hs.262958 hypothetical protein DKFZp434B044 11.33
413956 AI821351 Hs.193133 ESTs, Weakly similar to ALU7.HUMAN ALU S 11.29
407099 M94891 Hs.173609 pregnancy specific beta-1-glycoproteln 4 11.28
415447 Z97171 Hs.78454 myocllin, trabecular meshwork Inducible 11.09
451287 AK002158 Hs.26194 likely homolog of mouse Immunlty-assocla 11.03
442561 NM.013450 Hs.8383 bromodomaln adjacent to zinc finger doma 11.03
409981 AW516695 Hs.8438 ESTs 10.93
453180 N46243 Hs.110373 ESTs, Highly similar to T42626 secreted 10,88
407891 AA486620 Hs.41135 endomucln-2 10.87
406801 AW242054 Hs.190813 ribosomal protein L9 10,81
410545 U32324 Hs.64310 interleukin 11 receptor, alpha 10.79
442498 U54617 Hs.8364 Homo sapiens pyruvate dehydrogenase klna 10.76
425095 AW014160 Hs.182585 KIAA1276 protein 10.67
449101 AA205847 Hs.23016 G protein-coupled receptor 10.48
415550 L13720 Hs.78501 growth arrest-specific 6 10.41
444562 AA186715 Hs.336429 RIKEN cDNA 9130422N19 gene 10.40
428043 T92248 Hs.2240 uteroglobin 10.36
447261 NM 006691 Hs.17917 extracellular link domain-containing 1 10.33
410209 AI583661 Hs.60548 hypothetical protein PR01635 10.29
425078 NM 002599 Hs.154437 phosphodlesterase 2A, cGMP-stmulated 10.28
444769 AI191650 Hs.221436 ESTs 10.26
447726 AL137638 Hs.19368 matrilln 2 10.23
420225 AW243046 Hs.282076 Homo sapiens mRNA for KIAA1650 protein, 10.17
411988 AA455459 Hs.164480 ESTs, Weakly similar to T50609 hypotheti 10.17
425887 AL049443 Hs.161283 Homo sapiens mRNA; cDNA DKFZp586N2020 (f 10.15
456063 NM 006744 Hs.76461 retnol-blndiπg protein 4, Interstitial 10.03
458627 AW088642 Hs.97984 SRY (sex determining region Y)-box 17 (S 10.00
428412 AA428240 Hs.126083 ESTs 9.97
410016 AA297977 Hs.57907 small Inducible cytokine subfamily A (Cy 9.90
414449 AA557660 Hs.76152 decorin 9.88
447299 AF043897 Hs.18075 chromosome 9 open reading frame 3 9.82
421823 N40850 Hs.28625 ESTs 9.78
421218 NM 000499 Hs.72912 cytochrome P450, subfamily I (aromatc c 9.72
419119 AA583543 Hs.32135 ESTs 9.70
457056 NM 05534 Hs.177559 Interferon gamma receptor 2 (Interferon 9.65
423366 Z80345 Hs.127610 acyl-Coenzyme A dehydrogenase, C-2 to C- 9.63
417511 AL049176 Hs.82223 chordln-llke 9.60
427523 BE242779 Hs.179526 upregulated by 1,25-dlhydroxyvitamiπ D-3 9.51
434975 AA657884 Hs.314413 ESTs 9.49
452816 AA131789 Hs.61509 ESTs 9.47
443793 AA045290 Hs.25930 ESTs, Weakly similar to 2109260A B cell 9.47
441281 BE501247 Hs.144084 ESTs 9.44
408503 AW119059 ESTs, Weakly simllarto T12552 hypothet 9.40
412000 AW576555 Hs.15780 ATP-blπdlng cassette, sub-family A (ABC1 9.38
452307 R87866 Hs.95120 ESTs, Weakly simllarto HZHU hemoglobin 9.36
404246 Target Exon 9.33
436394 AA531187 Hs.126705 ESTs 9.28
431048 R50253 Hs.249129 cell death-Inducing DFFA-llke effector a 9.21
437176 AW176909 Hs.42346 calclneurin-blndlng protein calsarcln-1 9.18
444567 AV654020 ESTs, Weakly simllarto T26686 hypotheti 9.18
448274 AI268097 Hs.67317 Homo sapiens cDNA FLJ11775 fis, clone HE 9.17
428769 AW207175 Hs.106771 ESTs 9.15
449925 AI342493 Hs.24192 Homo sapiens cDNA FLJ20767 fis, clone CO 9.11
425498 AL096725 Hs.289010 DKFZP434B103 protein 9.10
438150 AA037534 Hs.342874 transforming growth factor, beta recepto 9.06
420174 AI824144 Hs.199749 ESTs 9.02
410066 AL117664 Hs.58419 DKFZP586L2024 protein 8.98
428024 Z29067 Hs.2236 NIMA (never In mitosis gene a)-related k 8.96
419407 AW410377 Hs.41502 hypothetical protein FLJ21276 8.92
453876 AW021748 Hs.110406 ESTs, Weakly similar to I38022 hypothet 8.90
445107 AI208121 Hs.147313 ESTs, Weakly similar to I38022 hypotheU 8.86
434096 AW662958 Hs.75825 plelomorphlc adenoma gene-like 1 8.86
407815 AW373860 Hs.183860 hypothetical protein FLJ20277 8.76 412649 NM 002206 Hs.74369 integrin, alpha 7 8.73
424651 AI493206 Hs.32425 ESTs 8.68
442560 AA365042 Hs.325531 ESTs, Weakly similar to 2004399A chromos 8.65
407826 AA128423 Hs.40300 calpaln 3, (p94) 8.63
442870 N45018 Hs.8769 hypothetical protein DKFZp761J17121 8.58
443062 N77999 Hs.8963 Homo sapiens mRNA full length Insert cDN 8.57
413856 D13639 Hs.75586 cyclin D2 8.53
422060 R20893 Hs.325823 ESTs, Moderately similar to ALU5.HUMAN A 8.51
442572 AI001922 Hs.135121 hypothetical protein FLJ22415 8.46
430468 NM 004673 Hs.241519 anglopoletn-llke 1 8.42
417640 D30857 Hs.82353 protein C receptor, endothelial (EPCR) 8.38
452165 R17489 Hs.28264 Homo sapiens mRNA; cDNA DKFZp564L0822 (f 8.36
414061 NM 000699 Hs.335493 amylase, alpha 2A; pancreatic 8.34
420139 NM 005357 Hs.95351 llpase, hormone-sensitive 8.34
418185 AW958272 Hs.347326 Intercellular adhesion molecule 2 (ICAM 8.30
422667 H25642 ESTs 8.29
419047 AW952771 Hs.90043 ESTs 8.28
417011 F08212 Hs.234898 ESTs, Weakly similar to 2109260A B cell 8.13
451529 AI917901 Hs.208641 ESTs 8.13
447540 AL135716 Hs.263780 ESTs 8.12
449787 AA005341 ESTs 8.06
409586 AL050214 Hs.55044 DKFZP586H2123 protein 8.02
446161 AA628206 Hs.14125 p53 regulated PA26 nuclear protein 8.01
435359 T60843 Hs.189679 ESTs 8.00
413190 AA151802 Hs.40368 adaptor-related protein complex 1, slgma 8.00
428748 AW593206 Hs.98785 Ksp37 protein 7.99
450787 AB006190 Hs.25475 aquaporin 7 7.96
428957 NM 003881 Hs.194679 WNT1 Inducible signaling pathway protein 7.95
427544 AI767152 Hs.181400 ESTs, Weakly simllarto I78885 serine/th 7.88
451583 AI653797 Hs.24133 ESTs 7.82
408988 AL119844 Hs.49476 Homo sapiens clone TUA8 Cri-du-chat regl 7.81
414555 N98569 Hs.76422 phospholipase A2, group IIA (platelets, 7.81
438411 H91928 Hs.169370 gb:ys81c10.r1 Soares retna N2b4HR Homo 7.81
439551 W72062 Hs.11112 ESTs 7.81
415165 AW887604 Hs.78065 complement component 7 7.81
408741 M73720 Hs.646 carboxypeptdase A3 (mast cell) 7.80
422033 AW245805 Hs.110903 olaudin 5 (transmembrane protein deleted 7.78
439310 AF086120 Hs.102793 ESTs 7.69
442831 AI798959 Hs.131686 ESTs 7.66
429697 AW296451 Hs.24605 ESTs 7.66
452390 AI864142 Hs.29288 hypothetical protein FLJ21865 7.65
421964 X73079 Hs.288579 polymeric Immunoglobulin receptor 7.65
427164 AB037721 Hs.173871 KIAA1300 protein 7.65
424580 AA446539 Hs.339024 ESTs, Weakly similar to A46010 X-llnked 7.65
448710 T62926 Hs.304184 ESTs 7.63
429580 AA346839 Hs.209100 DKFZP434C171 protein 7.58
410611 AW954134 Hs.20924 KIAA1628 protein 7.58
451154 AA015879 Hs.33536 ESTs 7.58
420311 AW445044 Hs.38207 Human DNA sequence from clone RP4-530I15 7.57
429640 U83508 Hs.2463 anglopoletin 1 7.57
421124 AI366452 Hs.184430 ESTs 7.55
409007 AL122107 Hs.49599 Homo sapiens mRNA; cDNA DKFZp434G0827 (f 7.52
411955 X05153 Hs.72938 lactalbumln, alpha- 7.49
407828 AW959500 Hs.49597 retnolc acid Induced 2 7.49
417355 D13168 Hs.82002 endothelln receptor type B 7.48
429297 X82494 Hs.198862 flbullπ 2 7.45
426406 AI742501 Hs.169756 complement component 1, s subcomponent 7.45
409472 BE154093 gb:PMl-HT0340-091199-001-h02 HT0340 Homo 7.42
449916 T60525 Hs.299221 pyruvate dehydrogenase kinase, Isoenzyme 7.38
433855 AA834082 Hs.307559 ESTs 7.37
442915 AA852875 Hs.8850 a dlslntegrln and metalloprotelnase doma 7.36
409385 AA071267 gb:zm61g01. Stratagene fibroblast (937 7.31
451573 AW130351 ESTs 7.30
444637 T19101 Hs.11494 fibullπ 5 7.29
442070 BE244622 Hs.8084 hypothetical protein dJ465N24.2.1 7.29
458081 AW014287 Hs.41587 RAD50 (S. cerevlslae) homolog 7.28
426992 BE244961 Hs.343200 FE65-UKE2 7.26
420570 AI453665 Hs.290870 ESTs, Weakly similar to I38588 reverse t 7.24
401929 C17001690:gi|6005701|refl,NP 009099.1| AT 7.23
449109 AW270992 Hs.120949 ESTs, Weakly similar to ALU7 HUMAN ALU S 7.21
453510 AI699482 Hs.42151 ESTs 7.18
405443 Target Exon 7.15
432519 AI221311 Hs.130704 ESTs, Weakly similar to BCHUIA S-100 pro 7.14
417054 AF017060 aldehyde oxldase 1 7.13
459501 AA854133 Hs.310462 ESTs 7.10
410057 R66634 Hs.268107 multlmerin 7.09
425438 T62216 Hs.270840 ESTs 7.09
447109 X69086 Hs.286161 Homo sapiens cDNA FLJ13613 fis, clone PL 7.07
444331 AW193342 Hs.24144 ESTs 7.04
452040 AW973242 Hs.293690 ESTs, Weakly similar to I38022 hypothet 7.04
453870 AW385001 Hs.8042 Homo sapiens cDNA: FLJ23173 (Is, clone L 7.02
413497 BE177661 gb:RC1-HT0598-020300-011-h02 HT0598 Homo 7.01
431728 NM.007351 Hs.268107 multlmerin 7.00
417780 Z43482 collagen, type XI, alpha 1 7.00
409060 AI815867 Hs.50130 necdiπ (mouse) homolog 6.99
423099 NM.002837 Hs.123641 protein tyrosine phosphatase, receptor t 6.98 419846 NM 015977 Hs.285681 Wllllams-Beuren syndrome chromosome regl 6.97
414516 AI307802 ESTs, Weakly similar to T43458 hypothet 6.97
425023 AW956889 Hs.154210 EDG-1 (endothelial differentiation, sph 6.93
426822 W78950 Hs.220823 ESTs 6.92
418283 S79895 Hs.83942 cathepsln K (pycnodysostosls) 6.91
435256 AF193766 Hs.13872 cytokine-llke protein C17 6.90
428722 U76456 Hs.190787 tissue Inhibitor of metalloprotelnase 4 6.89
423007 AA320134 Hs.196029 Homo sapiens mRNA for KIAA1657 protein, 6.88
408048 NM 007203 Hs.42322 A kinase (PRKA) anchor protein 2 6.87
426128 NM 001471 Hs.167017 gamma-amlnobutyric acid (GABA) B recepto 6.87
427283 AL119796 Hs.174185 ectonucleotde pyrophosphatase/phosphodl 6.86
426322 J05068 Hs.2012 transcobalamin I (vitamin B12 binding pr 6.85
429609 AF002246 Hs.210863 cell adhesion molecule with homology to 6.84
442662 U78168 Hs.8578 Rap1 guanlne-nucleotlde-exchange factor 6.82
408491 AI088063 Hs.7882 ESTs 6.79
451820 AW058357 Hs.199248 ESTs 6.77
409549 AB029015 Hs.54886 phospholipase C, epsilon 2 6.75
421255 BE326214 Hs.93813 ESTs 6.73
425869 AA524547 Hs.160318 FXYD domain-containing Ion transport reg 6.72
412567 AI750979 Hs.74034 Homo sapiens clone 24651 mRNA sequence 6.71
427019 AA001732 Hs.173233 hypothetical protein FLJ10970 6.71
443172 AW662964 Hs.199061 p300/CBP-assoclated factor 6.70
414716 AF199598 Hs.97044 Kv channel-Interacting protein 2 6.70
408731 R85652 Homo sapiens mRNA; cDNA DKFZp434F1928 (f 6.69
414522 AW518944 Hs.76325 Immunoglobulin J chain 6.67
412802 U41518 Hs.74602 aquaporin 1 (channel-forming Integral pr 6.63
425187 AW014486 Hs.22509 ESTs 6.61
407938 AA905097 Hs.85050 phospholamban 6.60
443282 T47764 Hs.132917 ESTs 6.60
444213 T79623 Hs.263351 ESTs 6.58
407492 S83198 gb:BPLP=basic prollne-rlch protein [huma 6.57
446714 W73818 Hs.110028 ESTs 6.57
421853 AL117472 Hs.108924 SH3-domain protein 5 (ponsln) 6.55
417728 AW138437 Hs.24790 KIAA1573 protein 6.54
452516 AA058630 Hs.29759 RNA POLYMERASE I AND TRANSCRIPT RELEASE 6.52
406692 L36607 gb:Homo sapiens (clone 22) pregnancy-spe 6.51
424252 AK000520 Hs.143811 hypothetical protein FLJ20513 6.49
420832 Z26248 Hs.99962 proteoglycan 2, bone marrow (natural kil 6.48
414665 AA160873 serum amyloid A1 6.48
443980 AI459140 Hs.109150 ESTs 6.47
414742 AW370946 Hs.23457 ESTs 6.47
418728 AW970937 Hs.293843 ESTs 6.46
419195 AW291165 Hs.25447 ESTs 6.45
453880 AI803166 Hs.135121 ESTs, Weakly similar to I38022 hypothet 6.43
444561 NM 004469 Hs.11392 c-fos induced growth factor (vascular en 6.41
433793 AW975959 Hs.107513 ESTs, Moderately similar to KIAA1058 pro 6.41
427809 M26380 Hs.180878 llpoprotein llpase 6.38
443627 AW138605 Hs.134198 ESTs 6.36
428411 AW291464 Hs.10338 ESTs 6.35
421368 L13283 Hs.103944 Homo sapiens (clone MG2-5-12) mucln (MG2 6.34
430234 N29317 KIAA1238 protein 6.34
423201 NM 000163 Hs.125180 growth hormone receptor 6.34
432030 AI908400 Hs.143789 ESTs 6.33
422722 H74219 Hs.269772 ESTs 6.33
411764 T40064 Hs.71968 Homo sapiens mRNA; cDNA DKFZp564F053 (fr 6.31
438414 AA806794 Hs.131511 ESTs 6.29
446939 AL133353 Hs.16606 CG1-32 protein 6.28
421465 AK001020 Hs.104627 Homo sapiens cDNA FLJ10158 fis, clone HE 6.28
453467 AI535997 Hs.30089 ESTs 6.27
435545 AA687415 Hs.28107 ESTs 6.25
407172 T54095 gb:ya92c05.s1 Stratagene placenta (93722 6.24
448406 AW772298 Hs.21103 Homo sapiens mRNA; cDNA DKFZp564B076 (fr 6.23
417788 AI436699 Hs.84928 nuclear transcription factor Y, beta 6.22
418452 BE379749 Hs.85201 C-type (calcium dependent, carbohydrate- 6.21
431177 NM 003304 Hs.250687 transient receptor potential channel 1 6.20
429331 H13881 Hs.143825 ESTs 6.20
419925 AA159850 Hs.93765 lipoma HMGIC fusion partner 6.19
453125 AW779544 Hs.115497 hypothetical protein FLJ22655 6.19
438303 AB028998 Hs.6147 KIAA1075 protein 6.15
427620 NM.003705 Hs.179866 solute carrier family 25 (mltochondrial 6.14
412568 AI878826 Hs.74034 caveolln 1, caveolae protein, 22kD 6.06
435487 W07343 Hs.182538 phosphollpld scramblase 4 6.05
420103 AA382259 Hs.95197 aldehyde dehydrogenase 1 family, member 6.02
418336 BE179882 glutathlone peroxidase 3 (plasma) 6.02
448782 AL050295 G-protelπ coupled receptor 116 (GPR116) 6.01
407939 W05608 Hs.312679 ESTs, Weakly similar to A49019 dyπeln he 5.99
430714 AA484757 Hs.287601 Homo sapiens cDNA FLJ13830 fis, clone TH 5.99
413630 AL036883 Hs.75450 delta sleep Inducing peptide, Immunoreac 5.98
417280 AW173116 Hs.250103 ESTs 5.98
424880 NM.000328 Hs.153614 retinltis pigmentosa GTPase regulator 5.97
413200 AA127395 Hs.222414 ESTs 5.97
431704 NM 006680 Hs.2838 malic enzyme 3, NADP()-dependent, mltoeh 5.96
447770 AB032417 Hs.19545 frizzled (Drosophila) homolog 4 5.96
421237 U25029 Hs.102761 Human glucocortlcold receptor alpha mRNA 5.95
449539 W80363 Hs.58446 ESTs 5.95
451108 AW268884 Hs.204387 ESTs 5.94 430520 NM 016190 Hs.242057 chromosome 1 open reading frame 10 5.94
419290 AI128114 Hs.112885 spinal cord-derived growth factor-B 5.93
445234 AW137636 Hs.146059 ESTs 5.92
446874 AW968304 Hs.56156 ESTs 5.92
422994 AW891802 Hs.296276 ESTs 5.89
425009 X58288 Hs.154151 protein tyrosine phosphatase, receptor t 5.89
422109 S73265 Hs.1473 gastrin-releaslng peptide 5.88
416336 R97949 Hs.24128 ESTs 5.87
441944 AW855861 Hs.8025 Homo sapiens clone 23767 and 23782 mRNA 5.86
447384 AI377221 Hs.40528 ESTs 5.86
407978 AW385129 Hs.41717 phosphodlesterase 1A, calmodulin-depende 5.86
454338 AW381251 gb:RCO-HT0297-301099-011-a08 HT0297 Homo 5.85
435266 AK001942 Hs.4863 hypothetical protein DKFZp566Al524 5.85
447571 AF274863 Hs.18889 DKFZP434M183 protein 5.85
432608 AI492660 Hs.170935 ESTs 5.83
412420 AL035668 Hs.73853 bone morphogenetc protein 2 5.79
428809 W56487 Hs.193784 Homo sapiens mRNA; CDNA DKFZp586K1922 (f 5.77
412622 AW664708 Hs.171959 ESTs 5.75
439177 AW820275 Hs.76611 ESTs, Weakly simllarto I38022 hypothet 5.75
450954 AI904740 Hs.25691 receptor (calcltonln) activity modifying 5.74
416889 AW250318 Hs.80395 mal, T-cell differentiation protein 5.74
418965 AI002238 Hs.11482 splicing factor, arglnine/serine-rich 11 5.74
436473 AI193122 Hs.132275 ESTs 5.73
430733 AW975920 Hs.121036 ESTs 5.73
426628 AW901932 Hs.278582 v-akt murine thymoma viral oπcogene homo 5.70
447894 AW204253 Hs.21912 ESTs 5.70
424585 AA464840 Hs.131987 ESTs 5.68
410485 AW750242 gb:RC1-BT0567-301299-011-e02 BT0567 Homo 5.66
439484 AW970218 Hs.135254 Homo sapiens clone 1 thrombospondln mRNA 5.64
459247 N46243 Hs.110373 ESTs, Highly similar to T42626 secreted 5.64
416749 AW068550 Hs.79732 flbulin 1 5.64
452093 AA447453 Hs.27860 Homo sapiens mRNA; cDNA DKFZp586M0723 (f 5.62
443510 NM 012190 Hs.9520 formyltetrahydrofolate dehydrogenase 5.62
407374 AA724738 Hs.131034 ESTs, Weakly similar to I78885 serine/th 5.62
417317 AW296584 Hs.293782 ESTs 5.62
407960 F34014 Hs.62914 ESTs 5.61
420733 AW291446 Hs.88651 ESTs 5.61
443605 H06865 Hs.134131 ESTs 5.59
406694 M94891 Hs.225932 pregnancy specific beta- -glycoprotein 7 5.57
421177 AW070211 Hs.102415 Homo sapiens mRNA; cDNA DKFZp586N0121 (f 5.56
427136 AL117415 Hs.173716 a dlslntegrin and metalloprotelnase doma 5.55
431981 AA664069 Hs.115779 ESTs 5.55
421712 AK000140 Hs.107139 hypothetical protein 5.53
426485 NM 006207 Hs.170040 platelet-derived growth factor receptor- 5.51
419150 T29618 Hs.89640 TEK tyrosine kinase, endothelial (venous 5.51
420517 AB011115 Hs.98507 KIAA0543 protein 5.50
450253 AL133047 Hs.24715 Homo sapiens mRNA; cDNA DKFZp434D0215 (f 5.49
402575 Rho GTPase activating protein 1 5.49
447974 R76886 gb:yi64b03.s1 Soares placenta Nb2HP Homo 5.49
429610 AB024937 Hs.211092 LUNX protein; PLUNC (palate lung and πas 5.48
424789 BE176694 Hs.279860 tumor protein, translatonally-controlle 5.48
428695 AI355647 Hs.189999 purlnerglc receptor (family A group 5) 5.46
436805 AA731533 Hs.270751 ESTs 5.46
459513 AI032946 gb:ox06g09.s1 Soares_fetal_llver_spleen_ 5.45
418481 M81945 CD34 antigen 5.44
414121 AA151719 Hs.95834 ESTs 5.44
410544 AI446543 Hs.95511 ESTs 5.44
407221 U25987 pregnancy specific beta-1 -glycoprotein 9 5.43
436062 AK000027 Hs.98633 ESTs 5.43
417696 BE241624 Hs.82401 CD69 antigen (p60, early T-cell activati 5.43
434230 AA551569 hypothetical protein PR02822 5.42
421429 NM 014922 Hs.104305 death effector filament-forming Ced-4-ll 5.41
438797 C16161 Hs.283040 hypothetical protein PR02543 5.40
454043 AW451951 Hs.29041 Homo sapiens cDNA FLJ14177 fis, clone NT 5.38
428531 AW274831 ESTs 5.37
437891 AW006969 Hs.6311 hypothetical protein FLJ20859 5.35
442713 D63203 Hs.184627 KIAA0118 protein 5.35
449282 AL048056 Hs.23437 Homo sapiens cDNA FLJ13555 fis, clone PL 5.34
407247 S83198 Hs.87198 basic prollne-rlch protein 5.34
414831 M31158 Hs.77439 protein kinase, cAMP-dependent, regulato 5.34
410116 AW630671 Hs.58636 squamous cell carcinoma antgen recognlz 5.33
426354 NM 004010 Hs.169470 dystrophln (muscular dystrophy, Duchenne 5.33
430265 L36033 Hs.237356 stromal cell-derived factor 1 5.33
433688 AA628467 Hs.112572 Homo sapiens cDNA FLJ14130 fis, clone MA 5.33
428939 AW236550 Hs.131914 ESTs 5.32
427605 NM 000997 Hs.337445 ribosomal protein L37 5.31
433138 AB029496 Hs.59729 semaphorln sem2 5.30
441319 AI354869 Hs.133081 ESTs, Weakly similar to T08700 hypotheti 5.30
450389 AW014016 ESTs 5.29
406686 M37755 gb:Human pregnancy-specific beta-1-glyco 5.29
428336 AA503115 Hs.183752 mlcrosemlπoproteln, beta- 5.29
442287 AW952703 Hs.8182 synaptlc nuclei expressed gene 1b 5.28
422431 AI769410 Hs.221461 ESTs 5.28
423023 N50128 Hs.173400 ESTs 5.25
413802 AW964490 Hs.32241 ESTs, Weakly simllarto S65657 alpha-1C- 5.25
446584 U53445 Hs.15432 downregulated in ovarian cancer 1 5.25 432128 AA127221 Hs.296502 Interleukin 1 receptor-like 1 5.25
411151 AW866497 gb:QV4-SN0024-170400-176-e07 SN0024 Homo 5.24
412330 NM 005100 Hs.788 A kinase (PRKA) anchor protein (gravin) 5.24
452422 AA521416 tumor necrosis factor receptor superfaml 5.24
424244 AV647184 Hs.143601 hypothetical protein hCLA-lso 5.24
428280 H05541 Hs.183428 sarcospan (Kras oncogeπe-associated gene 5.23
451683 AI808964 Hs.207673 ESTs 5.23
441723 R72137 Hs.7949 DKFZP586B2420 protein 5.22
408000 L11690 Hs.198689 bullous pemphigold antigen 1 (230/240kD) 5.22
439091 AA830144 Hs.135613 ESTs, Moderately similar to I38022 hypot 5.21
439411 AA044876 Hs.58043 ESTs, Weakly similar to CYA2.HUMAN ADENY 5.20
419917 AA320068 Hs.93701 Homo sapiens mRNA; cDNA DKFZp434E232 (fr 5.20
458616 AV656098 Hs.172382 betalne-homocysteine methyltransferase 2 5.19
444523 AW409958 Hs.323396 hypothetical protein RP1-317E23 5.19
406714 AI219304 Hs.266959 hemoglobin, gamma G 5.19
437140 AA312799 Hs.283689 activator of CREM In tests 5.19
427890 AA435761 ESTs 5.18
408776 AA057365 ESTs, Weakly simllarto I38022 hypothet 5.18
407571 AI446183 Hs.9572 ESTs, Highly similar to CYA5.HUMAN ADENY 5.17
407183 AA358015 gb:EST66864 Fetal lung III Homo sapiens 5.16
414005 AA134489 ESTs 5.16
449679 AI823951 Hs.129700 tollold-like 1 5.15
436306 AA805939 Hs.117927 ESTs 5.15
408221 AA912183 Hs.47447 ESTs 5.14
412668 AA456195 hypothetical protein FLJ14621 5.14
443547 AW271273 hypothetical protein FLJ12666 5.14
449365 AW968261 Hs.118913 ESTs, Moderately similar to T46371 hypot 5.12
433165 AA578904 Hs.292437 ESTs 5.12
417067 AJ001417 Hs.81086 solute carrier family 22 (extraneuronal 5.12
437948 AA772920 Hs.303527 ESTs 5.12
447391 AI377444 Hs.64245 ESTs, Weakly simllarto S65824 reverse t 5.11
437652 AF036144 Hs.5734 meπlngioma expressed antigen 5 (hyaluron 5.11
434633 AI189587 Hs.120915 ESTs 5.10
421341 AJ243212 deleted In malignant brain tumors 1 5.10
420908 AL049974 Hs.100261 Homo sapiens mRNA; cDNA DKFZp564B222 (fr 5.10
410526 R05652 Hs.64125 Homo sapiens clone 24617 mRNA sequence 5.09
412460 AW953287 Hs.83071 ESTs 5.09
451245 AA016218 Hs.58231 ESTs 5.08
444880 AW118683 Hs.154150 ESTs 5.08
448425 AI500359 ESTs 5.07
421932 W51778 Hs.323949 kangal 1 (suppression of tumorlgenlclty 5.06
433854 AA610649 Hs.333239 ESTs 5.06
451742 T77609 ankyrin 2, neuronal 5.05
431176 AI026984 Hs.293662 ESTs 5.05
445399 AI681906 Hs.4786 Homo sapiens cDNA: FLJ22849 fis, clone K 5.05
437027 AB023235 Hs.5400 KIAA1018 protein 5.05
432527 AW975028 Hs.102754 ESTs 5.04
433740 AA934994 Hs.112628 ESTs 5.03
431638 NM 000916 Hs.2820 oxytocln receptor 5.02
436037 AA917639 Hs.13063 ESTs 5.02
423488 AW748714 Hs.194720 gb:QV3-BT0294-241199-025-c01 BT0294 Homo 5.02
426464 NM 004334 Hs.169998 bone marrow stromai cell antigen 1 5.02
450697 AW152166 Hs.182113 ESTs 5.01
436169 AA888311 Hs.17602 Homo sapiens cDNA FLJ12381 fis, clone MA 5.01
453143 AA382234 protein tyrosine phosphatase, receptor t 5.01
414545 AA149287 Hs.76605 ESTs 5.00
421126 M74587 Hs.102122 Insulln-llke growth factor binding prate 4.99
413401 AI361861 Hs.118659 ESTs 4.98
436919 AW297307 Hs.204562 ESTs 4.97
453828 AW970960 Hs.293821 ESTs 4.96
418318 U47732 Hs.84072 transmembrane 4 superfamlly member 3 4.95
408669 AI493591 Hs.78146 platelet/endothellal cell adhesion molec 4.94
414919 AW087337 Hs.194461 ESTs 4.94
438608 AI380529 Hs.44628 ESTs 4.94
414138 AA135884 Hs.3772 ESTs 4.94
434365 AI073378 Hs.126793 ESTs 4.94
408242 AA251594 Hs.43913 PIBF1 gene product 4.94
437773 U24186 Hs.283018 replication protein A complex 34 kd subu 4.93
445529 H14421 Hs.180513 ATP-biπdlπg cassette, sub-family A (ABC1 4.93
434389 AA971235 Hs.128098 ESTs 4.90
407758 D50915 Hs.38365 KIAA0125 gene product 4.90
424776 AI867931 Hs.164595 ESTs 4.89
448122 AW665656 Hs.173187 ESTs 4.88
TARI F SB
Pkey: Unique Eos probeset Identifier number
CAT number Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accession 421998 133592.1 BI757233 BG911321 BF351759 AW244016 AW026834 AW024260 AI420138 AA779354 AI093360 AI934858 AW151292 AI373133 AI335587
AI969728 AA101632 BE218525 AI802114 AI783721 AA845265 AW088826 AI832852 F03967 AI611148 AI720358 AW293764 N91161
R79192 W85852 AW771263 BG820263 BG012B64 R74441 R86080 W04256 BE707244 BF899452 BE327552 BE669500 AI492388
AI241532 BF448184 AI209012 AA886528 N70309 AW582776 BF110563 BF448329 BE326537 AW770471 BF444926 BE674147 AI793266
AI991774 AI807726 AI218667 AA301750 R44328
411962 2307710.1 AA099050 AA099526T47733 414496 1526.1 AK058006 BF724822 W65303 AW887764 AW023806 Z25353 AW022095 AA730973 W00417 W73819 BF982096 AI927669 AW188021
AW770478 AI913512 AA604358 AI697341 AI691028 AI338392 AI079403 H97538 AI144448 AI253102 AI051402 AI335900 AI868132
N28900 H9B465 AF268386 AI799915 AI819228 BE048413 AW304723 AI819923 BF223106 AA155907 AW298079 BF055272 BF446804
BF197697 W58588 BF197538 AA032180 AA992597 AW590254 AA027824 AI129369 AI131331 AI655843 AA932907 AW104493 AI150615
BF110226 AW172271 AI312659 AA057312 BE673669 AA722984 AW104985 AM 29232 AI078648 AI653086 AI703481 AW515897 AI352206
N67076 AW297281 AI686162 AA029184 AI610743 AW772016 AI091778 W65401 AI687374 AI218085 AI765158 AI018002 AI653068
AI335704 AI520850 AW275228 AW275204 AI420247 AA975336 AI697042 AW182235 AA736386 AI281682 AW169698 AW263325
BE645834 AI377438 AI146706 AA613808 AA716538 BI496247 AA032248 AI698930 AI193399 N70026 H86792 AA404489 W61267
BF447230 AA910805 AA150774 AA621907 AA902526 AI827634 AW022037 BF059000 BI496246 BG577007 BG571077 AA460779
AW816890 AW816893 AW816891 AA029183 AA010295 H86850 T83320 BE160823 H12925 N40087 AA096372 BE160847 AW816892
AW816889 AW816882 AW816868 AW816941 AW816578 AW816940 AW816577 AI431628 AI828113 AA033677 AA033654 AA452704
AA317582 AA346971 BF836584 H48669 BI861605 BG925200 AA463277 H89048 AA155952 W03252 W01510 W00915 W58589 AA164519
N24017 N24622 N27149 N70109 R43771 AA010296 W84611 H98889 H88965 AW594424 AA034139 AA065223 N99696 BG981481 N94371
AA767970 W47146 N70977 H05510 W61268 T90796 AA164518 W47244 AA150883 AA034138 BF338483 F13671 H51317 W72716 N21488
AI188071 AI370541 AI754442 AA148524 AI749182 W95221 W92522 R20385
407102 7177.2 AW945170 BF930905F33652 BG057818 AI368018 AI421485 AI300352AI378525AI264177AI276281 AI245302AI281050AI190036
AW451438 AW242903 AA910870 F22289 F19647 F22375 AW473816 BF445785 AA774528 F33447 C01077 AW772227 F17759 H42812
R09701 AA349096 R48772 H42892 H42537 R47898 N28263 H25721 F32386 H43971 R48205 F21390 H45809 AA007629 R47897 R83734
H45844 AW983653 H43970 H42536 H24495 R48875 H42961 H22079 RB6018
406800 0.0 AA505535 412295 133592.1 BI757233 BG911321 BF351759 AW244016 AW026834 AW024260 AI420138 AA779354 AI093360 AI934858 AW151292 AI373133 AI335587
AI969728 AA101632 BE218525 AI802114 A1783721 AA845265 AW088826 AI832852 F03967 AI611148 AI720358 AW293764 N91161
R79192 W85852 AW771263 BG820263 BG012864 R74441 R86080 W04256 BE707244 BF899452 BE327552 BE669500 AI492388
AI241532 BF448184 AI209012 AA886528 N70309 AW582776 BF110563 BF448329 BE326537 AW770471 BF444926 BE674147 AI793266
AI991774 AI807726 AI218667 AA301750 R44328
408503 24663.2 NM.054110 BC014789 BI552129 BG896227 BG900557 AY035399 AW119059 BF432376 AW629242 AA971319 AI378176 AI275884
AA236602 BG898257 BG897636 BG900588 AF361251 BG926353 BG714178 AA368180 BG896473 BG715977 BG900230 BG901163
BF342939
444567 42058.1 BE048349 AW974054 R79064 AA854763 AA780852 AW129141 AI061419 AW469162 AA602558 AA975901 H65073 H94455 AA969673
BE048171 R63499 R92783 N68673 R62964 R31280 AA873363 R92768 AI740671 N41012 H72843 N54939 N91687 H58308 N53116
AV650793 AV650271 BI489336 R28494
422667 224778.1 AI758223 AW469334 BF940841 AW080348 AI270363 AI055892 BE464168 BF431797 BE350144 BF448739 AI693409 BF432999 D62848
AA398070 AI383375 AW611490
449787 79759.1 AW975633 AW961632 AA322539 AW513289 AI864190 AW073506 AI016894 AA747635 AA730405 AA418033 AI609549 AI873981
AA005341 BE182658 AA004291
409472 813633.1 BE162685 BE154093 BE154085 409385 110758.1 T65940 T64515 AA071267 AA071334 451573 625119.1 AW338699 AI803973 AW130351 417054 124052 BG533564 BG618564 AW296119 AI269233 BF508328 AW364777 AW292258 AA371049 AI452471 AI092522 BG618376 AL049080
AA631068 BG564643 T53833 AV702544 BG533452 AV705004 AA588281 T28665 BG569026 AV646874 AV647253 AV647455 AV647749
BI759444 AV652457 AV695354 AV696010 AV697248 BG617586 AV722549 AI435836 AI590676 AI245019 AW338243 AA530898 D52191
AI435352 D57473 BG566952 AI420505 AA035245 AV704972 BG564113 AI439237 AI287456 AV695686 AA349017
413497 1518002.1 BE177661 H06215 BE144709 BE144829 417780 2147534.1 R14659Z43482 52906 414516 60847.1 AK057782 AI146454 BG703115 AI765980 AI948611 AA889263 AA947457 BG547193 H11947 Z38147 F10426 BF447329 H11946 T74968
F06195 BG548563 AI004988 AA148735 AI307802 A1439791 BE041453 AI984904 AA148734 F12823
408731 11725.2 AF305826 BE350971 AI765355 AW172600 AI310231 BM271766 AI547292 AW612019 AI674617 AW138666 AI147629 AI147620 BF857810
BF886300 BF885952 BF886303 BF885956 BG565497 BE670834 AA114025 BF886396 BF886928 AV750861 D62864
407492 65295.1 S83198 NM.021225 BG212392 BG218751 BG191209 BG212926 BG185436 406692 00 L36607 414665 23751.3 BG567713 AW665841 AI814924 AW978339 AW264036 AI373950 AW183157 AW082249 AI201658 AI364196 AA150743 AA160873
AA453757 BF871646 BF871640 AA565311 AA989511 10152 AA807154 T77900 AV751591
430234 1746.1 AW025803 AL137567 AI760919 BE552289 AW082686 AA913951 BE501313 AV756373 BE048863 AA8281858G151502 AI655583
AW473377 AI949888 AA453495 AW130287 AI222766 AI862122 AI309288 AL038626 AA714749 AI719007 W95486 N29317 AW589706
AA905486 AI744057 AA759318 AI084950 AI273294 BF835579 AW235310 AI914478 BF887920 R21864 AI479541 AW189671 AW235752
AI762157 BG698714 AA461269 AA460813 W95524 AA301369 AI760649 BF854009 AW303856 H42831 AV737305 H03702 R22396 R65961
407172 452462.1 BG925072 BG925045 AV738744 T54095 T54186 BI000208 BI003704 BI002312 BG990736 BI000200 BI004083 BI004085 BI000196
BG990731 BG990735 418336 58817.1 AW969583 BI772505 BE179578 AI493714 AI937718 AA663709 BI868925 AW138743 AI911314 BE645538 BG911947 AI380325 AI265803
W56175 AI658779 AI675997 AW665991 AI459263 AI420121 Z38874 AA570115 AW301008 AA216257 BF062662 BI772789 H05989
BF085523 BI001277
448782 34980.1 AB018301 AL050295 BF513128 AW385080 AL551708 AI352542 AI829703 AI819388 AW629019 AW073189 AW273857 AW118768
AI453845 AI452494 AA886341 AI057144 AA904647 AI423547 AW263913 AI094774 AI434419 AI039546 AI002491 AI240412 Z25099
AA995178 AW050649 AW026140 AI796309 AI5840128E166666 AI767991 AI309041 AA724059 AI695284 AI245095 T63971 Z40627
BE166681 BG570071 BF921915 BI562702 BG506502 AV658066 R48378 AA121543 AI096938 AA618131 H40993 R48277 AI352281
BG540263 BG538901 N95226 AI356752 AI221152 Z28777 R16574 AW966449 AA044116 AW797518 BI010405 AA044288 AI093508
BE140169 T64039 BG433106 AW130367 AW130361 N73937 AA127680 AW044037 AI096437 AA384077 BF941499 T93764 BG003285
454338 788429.-2 AW381251
410485 10284431 AW750242T68507
447974 10922391 BG944967 AI453674 R77049 R76886
459513 417837.1 AV704062 BE162284 AI032946 BF360636
418481 17381.1 S53911 NM.001773 AL572644 AL550179 AI688653 AW025002 AW614285 AU158779 AI017002 AA434387 AI252665 AI262206 AU147582
AI144193 AW952860 AI128776 AI017793 AI160509 AA906021 AI149563 AU154950 AI128488 W74409 AI970362 AI141453 AU158772
W58493 BM148338 R73091 AW020496 BI491517 AA022917 AI432610 AI879448 R69099 AI708954 AW014274 AA483672 AA528783
AA912271 AI926942 BE677587 AI874217 AA152376 AA640408 AI287334 BF830285 AA311473 C18678 AA922603 C00910 AI124073
R38730 AA043439 W94644 W5B646 AA664247 BE061934 H01096 R69613 AI383162 AU133723 AA311526 R67942 H01097 H72113
R72430 R39494 AV744074 AA535925 BI759288 BI052385 BF854687 AW608286 AA043438 R72478 AL513811 R69214 AA188435
AA054965
434230 411101 AF119900 NM.018539 AA702388 N53043 BF351064 N70103 AI207469 AA551569 AW383189 W00906 W00935 N54252 428531 715072.1 AI672553 AW274831 AA429897 AA446046 AA860950 450389 2018.25 AI694475AW341358AW014016 411151 1071416.1 AW819775AW866497 AW819868AW866602AW866561
452422 10123.3 AK056500 AL520733 AA521416 AW967877 AI799849 AA470754 AI674241 AI343684 BF589270 AA026154 AI473803 AW612523 AI344466
AI344464 AI216171 AA055926 AA255890 BF967590 AA055329 AA026153 W52679 AA135902 AI721140 C14114 R43875 AI761376 R58888
AA135901 BF849170 AA725347 A1908777 AA719606
427890 1373988.1 AA417099 AA435761 AA972917 AI660387
408776 106302.1 BF057799 BE218747 T15720AA057365 AI811370
414005 259333.1 AW968220 AA259126 AA287352 AA279767 AI479143 AA863044 AA134489 H49266 L32048
412668 33230.1 AK057749 AI701055 AA115476 AI633570 AI435607 AW173392 AI092468 AI989318 AA833891 AW295964 AI804107 AI767415 AI473818
AI076758 AA278949 AA428547 N31385 H82560 AA464804 AA809073 AA832476 AW295298 BF108690 AI492243 N22394 AA487175
AA431891 AWO70941 AA278823 AA707840 AI346067 AI184307 AA936342 AI288633 AA425697 AI435960 AI301433 AA993394 AI917652
AA487234 AA490964 AA937925 AI301378 AI783840 AI093652 AA723864 BF00137881818971 BI762256 AW957064 BG720359 BIB21176
BI906440 AI472868 AL523506 BF962934 BF960650 BI837618 BF956256 AA487349 BF961475 AA354431 AA115452 AA491157 N75632
BF962141 AL562216 BI754640 N24091 R00062 AI963686 T56529 AU185624 T56460 H97658 BI752843 BI819132 AA210796 443547 137089.2 AV645808 AA701657 AW271273 AI796734 AI472316 AI017531 AI061178 BF109096 AA548964 N83805 AA131648 AA156589 BE708349
AW952494 D30877 AV684717 Z24837 F00167 BF576150 T63841 R78995 N87474
421341 1407.1 NM.007329 AF159456 AJ243212 AJ297935 AA295769 NM 017579 AJ243224 AI492875 AI796676 AI749838 AA918144 AI814590
AI923531 BF513992 AI720725 AI150879 AI279072 AW612904 AI492104 AI284510 AI141231 AA613554 AW662148 AW769047 AA565985
AW612888 AU100513 BG955585 BG955588 AA295763 BE829414 BF760645 BG954398 AA295332 AA295795 BE932867 AW769569
T89953 BE934311
448425 506563.1 AW005628 AI500359 AW275593 451742 15505.1 BC017986 AI129314 BF594240 N80108 AI273593 AI292203 AI341883 AI093196 AI090550 AI144158 AW613047 AL043865 N78951 D44679
BE349232 AW511871 AL537825 AL134066 F13505 AW954583 AA351161 T77609 BG283250 C15501 D81753 R60790 F04232 AL537824
AI096710 AI307186 AA458658 AW614225 AI804466 BF446326 AI799735 BF591932 AW129277 AI252220 AI217036 AW316545 AI287987
AI880082 H15099 N89711 AA054086 F26355 AI362724 N80775 Z39382 AI910523 T33415 R42392 AA455356 AA975079 AA894809
T33395 F03344 BF726212 N53354 AA019494 AA311664 F10695 R41849 AA019744 AW299413 AI372486 AI384058 N98737 N64675
AI953492 AI372484 R39245 W31177 BF679932 BF377203 BF977609 BI768322 BI764551
453143 10116.6 BG542081 BF793365 AI371013 AI147536 AW005418 AA416767 AI083516 AI698032 AA410929 AI936116 AI079893 AA747741 BF940413
BM007681 F12285 N75819 AI971415 AA032249 AW867908 AW867914 AI520867 BG990651 AA570507 AA036654 AA063585 AA873147
AI538117 AA382234 T66232 BE272411 AA834031 BG122734 BI769788 W55850 AW879266
TABLE 5C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank Identifier (GI) numbers. 'Dunham I. et al." refers to the publication entted "The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495. Strand: Indicates DNA strand from which exons were predicted. NLpositlon: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLpositlon
403593 6862650 Minus 62554-62712,69449-69602
404246 7406725 Plus 82477-82628,82721-82817,82910-83071,8314
401929 3810670 Minus 3167-3286,4216-4310
405443 7408143 Plus 90716-90887,101420-101577
402575 9884830 Minus 109742-109883
TABLE 6A About 1251 genes upregulated In luππ metastases to the brain relative to normal lung
Pkey Unique Eos probeset Identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene ttle
R1 90th percentile of lung metastases to the brain Als divided by the 90th percentile of normal lung Als, where the minimum In the numerator and denominator was set to 20
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
406690 M29540 Hs 220529 carclnoembryonlc antgen related cell ad 5534 385
412719 AW016610 Hs 816 ESTs 31 39 18
422487 AJ010901 Hs 198267 mucln 4, tracheobronchlal 2900 36101
409103 AF251237 Hs 112208 XAGE-1 protein 2798 1389
444381 BE387335 Hs 283713 hypothetcal protein BC014245 2721 71
422963 M79141 Hs 13234 sphlngoslne 1 phosphate phosphohydrolase 2663 39
426682 AV660038 Hs 2056 UDP glycosyltransferase 1 family, polype 2499 48
414430 AI346201 Hs 76118 ublqultin carboxyl terminal esterase L1 2378 20
433447 U29195 Hs 3281 neuronal pentraxin II 2305 60113
429500 X78565 Hs 289114 hexabrachlon (tenascln C, cytotactin) 21 72 55 100
411908 L27943 Hs 72924 cytldlne deamlnase 21 57
409632 W74001 Hs 55279 serine (orcystelπe) protelnase inhibito 2087
431566 AF176012 Hs 260720 J domain containing protein 1 1992
425057 AA826434 Hs 1619 achaete scute complex (Drosophila) homol 1918
456508 AA502764 Hs 123469 ESTs Weakly simllarto AF2088551 BM 01 1904
419078 M93119 Hs 89584 Insullnoma associated 1 1886
415906 AI751357 Hs 288741 Homo sapiens cDNA FLJ22256 fis, clone H 1881
419875 AA853410 Hs 93557 proenkephalln 1839
455601 AI368680 HS 816 SRY (sex determining region Y) box 2 1760
428839 AI767756 Hs 82302 Homo sapiens cDNA FLJ14814 fis, clone NT 1709
439897 NM 015310 Hs 6763 KIAA0942 protein 1706
417433 BE270266 Hs 82128 5T4 oncofetal trophoblast glycoprotein 1689
449230 BE613348 melanoma cell adhesion molecule 1673
452838 U65011 Hs 30743 preferentially expressed antigen In ela 1651
431958 X63629 HS 2877 cadherin 3, type 1 P cadheπn (placenta 1643
453857 AL080235 Hs 35861 Ras-lnduced senescence 1 (RIS1) 1632
430130 AL137311 Hs 234074 Homo sapiens mRNA, cDNA DKFZp761G02121 ( 1592
429228 AI553633 hypothetical protein MGC33630 1572
424922 BE386547 Hs 217112 hypothetical protein MGC10825 1568
447329 BE090517 ESTs, Moderately similar to ALU8.HUMAN A 1567
408393 AW015318 Hs 23165 ESTs 1564
436217 T53925 Hs 107 fibrinogen like 1 1560
421948 L42583 Hs 334309 keratin 6A 15 17
452240 AI591147 Hs 61232 ESTs 1502
418738 AW388633 Hs6682 solute carrier family 7, (cationic amino 1489
452487 AW207659 Hs 6630 Homo sapiens cDNA FLJ13329 fis, clone OV 1482
422440 NM M4812 Hs 116724 aldo-keto reductase family 1, member B10 1477
424001 W67883 Hs 137476 paternally expressed 10 1472
408949 AF189011 Hs 49163 putative πbonuclease III 1455
431933 AI187057 Hs 132554 ESTs 1454
452747 BE153855 Hs 61460 Ig superfamily receptor LNIR 1448
423634 AW959908 Hs 1690 hepartn binding growth factor binding pr 1444
432467 T03667 Hs 239388 Human DNA sequence from clone RP1 304B14 14 36
449722 BE280074 Hs 23960 cyclln B1 1429
412490 AW803564 Hs 288850 Homo sapiens cDNA FLJ22528 fis, clone H 1427
406399 NM.003122' Homo sapiens serine protease 14 16
423073 BE252922 Hs 123119 MAD (mothers against decapentapleglc, Dr 1394
418329 AW247430 Hs 84152 cystathionlne beta synthase 1391
428450 NM 014791 Hs 184339 KIAA0175 gene product 1386
427871 AW992405 Hs 59622 Homo sapiens, clone IMAGE 3507281, mRNA, 1356
428342 AI739168 Homo sapiens cDNA FLJ13458 fis, clone PL 1348
426283 NMJ03937 Hs 169139 kynurenlnase (L kynurenlne hydrolase) 1345
411305 BE241596 Hs 69547 myelin basic protein 1341
407137 T97307 gb ye53h05 s1 Soares fetal liver spleen 1341
410082 AA081594 Hs 158311 Musashl (Drosophila) homolog 1 1313
433485 AI493076 Hs 306098 aldo keto reductase family 1, memberC2 1309
434826 AF155661 Hs 22265 pyruvate dehydrogenase phosphatase 1305
425234 AW152225 Hs 165909 ESTs, Weakly simllarto I38022 hypothet 1305
437762 T78028 Hs 154679 synaptotagmin I 1298
427528 AU077143 Hs 179565 mlnlchromosome maintenance deficient (S 1291
426514 BE616633 Hs 170195 bone morphogenetc protein 7 (osteogenlc 1282
424308 AW975531 Hs 154443 mlnlchromosome maintenance deficient (S 1272
416655 AW968613 Hs 79428 BCL2/adenovirus E1B 19kD Interacting pro 1261
427344 NM.000869 Hs 2142 5 hydroxytryptamlne (serotonin) receptor 1258
432441 AW292425 Hs 163484 Intron of hepatocyte nuclear factor-3 al 1257
429170 NM 001394 Hs 2359 dual specificity phosphatase 4 1255
446080 AI221741 Hs 117777 ESTs 1254
414683 S78296 Hs 76888 hypothetical protein MGC12702 1254
449845 AW971183 Hs 6019 DnaJ (Hsp40) homolog, subfamily C, membe 1225
410442 X73424 Hs 63788 proplonyl Coenzyme A carboxylase, beta p 1220
422511 AU076442 Hs 117938 collagen, type XVII, alpha 1 1210
442547 AA306997 Hs 217484 ESTs, Weakly simllarto ALU1.HUMAN ALU S 11 92 412446 AI768015 ESTs 11.86
414219 W20010 Hs.75823 ALL1-fused gene from chromosome 1q 11.78
414825 X06370 Hs.77432 epidermal growth factor receptor (avian 11.74
422880 AF228704 Hs.193974 glutathloπe reductase 11.73
446469 BE094848 Hs.15113 ho ogentsate 1,2-dioxygenase (homogentl 11.65
412636 NM 004415 desmoplakln (DPI, DPII) 11.63
452099 BE612992 Hs.27931 hypothetical protein FLJ10607 simllarto 11.54
458692 BE549905 Hs.231754 ESTs 11.52
431211 M86849 Hs.323733 gap Junction protein, beta 2, 26kD (conn 11.42
413554 AA319146 Hs.75426 secretogranln II (chromogranin C) 11.30
442432 BE093589 Hs.38178 hypothetical protein FLJ23468 11.28
429922 Z97630 Hs.226117 H1 hlstone family, member 0 11.22
403149 NM_001450:Homo sapiens four and a half L 11.20
424098 AF077374 Hs.139322 small prollne-rlch protein 3 11.15
408298 AI745325 Hs.271923 Homo sapiens cDNA: FLJ22785 fis, clone K 11.13
426539 AB011155 Hs.170290 discs, large (Drosophila) homolog 5 11.09
432460 H12912 Hs.274691 adenylate kinase 3 11.06
427398 AW390020 Hs.20415 chromosome 21 open reading frame 11 11.02
433339 AF019226 Hs.8036 glioblastoma overexpressed 10.98
436420 AA443966 Hs.31595 ESTs 10.97
412140 AA219691 Hs.73625 RAB6 Interacting, klnesln-like (rabklnes 10.97
434001 AW950905 Hs.3697 anglotenslnogen 10.97
409361 NM 005982 Hs.54416 sine oculls homeobox (Drosophila) homolo 10.94
439963 AW247529 Hs.6793 platelet-activating factor acetylhydrola 10.87
407833 AW955632 Hs.66666 ESTs, Weakly simllarto S19560 prollπe-r 10.84
433160 AW207002 Hs.134342 TASP for tests-specific adriamycin sens 10.78
426827 AW067805 Hs.172665 methylenetetrahydrofolate dehydrogenase 10.64
446342 BE298665 Hs.14846 solute carrier family 7 (catonic amino 10.58
410337 M83822 Hs.62354 cell division cycle 4-llke 10.58
416854 H40164 Hs.80296 Purklnje cell protein 4 10.58
418327 U70370 Hs.84136 paired-like homeodomaln transcription fa 10.55
425071 NM 013989 Hs.154424 delodlπase, lodothyronlne, type II 10.53
409041 AB033025 Hs.50081 Hypothetical protein, XP.051860 (KIAA119 10.52
436291 BE568452 Hs.344037 protein reguiatorof cytokinesis 1 10.50
446639 AI016826 Hs.342148 ESTs 10.48
421110 AJ250717 Hs.1355 cathepsin E 10.47
417308 H60720 Hs.81892 KIAA0101 gene product 10.47
428931 AA994979 Hs.98967 ATPase, H()-traπsportlng, lysosomal, non 10.46
425465 L18964 Hs.1904 protein kinase C, iota 10.42
423472 AF041260 Hs.129057 breast carcinoma amplified sequence 1 10.40
433001 AF217513 Hs.279905 clone HQ0310 PRO0310p1 10.39
429663 M68874 Hs.211587 phospholipase A2, group IVA (cytosollc, 10.36
424378 W28020 Hs.167988 neural cell adhesion molecule 1 10.33
447033 AI357412 Hs.157601 Predicted gene: Eos cloned; secreted wΛ/ 10.29
413517 N76712 Hs.44829 ESTs, Weakly simllarto I38022 hypotheti 10.27
422163 AF027208 Hs.112360 promlnln (mouse)-like 1 10.22
436469 AK001455 Hs.5198 Down syndrome critical region gene 2 10.21
409187 AF154830 Hs.50966 carbamoyl-phosphate syπthetase 1, mltoeh 10.21
428966 AF059214 Hs.194687 cholesterol 25-hydroxylase 10.20
443683 BE241717 Hs.9676 uncharacterized hypothalamus protein HT0 10.16
426793 X89887 Hs.172350 HIR (hlstone cell cycle regulation defec 10.13
409269 AA576953 Hs.22972 steroid 5 alpha-reductase 2-llke; H5AR g 10.09
428862 NM.000346 Hs.2316 SRY (sex determining region Y)-box 9 (ca 10.05
414869 AA157291 Hs.21479 ublnuclein 1 9.98
407633 NM 007069 Hs.37189 simllarto rat HREV107 9.97
410817 AI262789 Hs.93659 protein disulfide Isomerase related prat 9.95
442355 AA456539 Hs.8262 lysosomal-assoclated membrane protein 2 9.91
448474 AI792014 Hs.13809 hypothetical protein FLJ10648 9.87
430589 AJ002744 Hs.246315 UDP-N-acetyl-alpha-D-galactosamlπe:polyp 9.84
456844 AI264155 Hs.152981 CDP-dlacylglycerol synthase (phosphatlda 9.83
425322 U63630 Hs.155637 protein kinase, DNA-actlvated, catalytc 9.83
416294 D86980 Hs.79170 KIAA0227 protein 9.81
446204 AI279809 Hs.150019 ESTs 9.77
424954 NM 000546 Hs.1846 tumor protein p53 (Ll-Fraumenl syndrome) 9.75
426559 AB001914 Hs.170414 paired basic amino acid cleaving system 9.73
441020 W79283 Hs.35962 ESTs 9.68
431797 BE169641 Hs.270134 hypothetical protein FLJ20280 9.66
407355 AA846203 Hs.193974 ESTs, Weakly simllarto ALU1.HUMAN ALU S 9.66
446839 BE091926 Hs.16244 mltotio spindle colled-coll related prat 9.65
434063 AA018893 Hs.3727 unr-lπteracting protein 9.63
432886 BE159028 Hs.279704 chromatn accessibility complex 1 9.57
449349 AI825386 hypothetical protein FLJ21939 similar to 9.56
453884 AA355925 Hs.36232 KIAA0186 gene product 9.54
412519 AA196241 Hs.73980 troponin T1, skeletal, slow 9.53
428004 AA449563 Hs.151393 glutamate-cysteine llgase, catalytc sub 9.51
440274 R24595 Hs.7122 scraple responsive protein 1 9.49
423732 AF058056 Hs.132183 solute carrier family 16 (monocarboxyllc 9.46
427674 NM 003528 Hs.2178 H2B hlstone family, member Q 9.43
441633 AW958544 Hs.112242 normal mucosa of esophagus specific 1 9.42
413753 U17760 Hs.75517 lamlnln, beta 3 (nlceln (125kD), kalinln 9.41
452046 AB018345 Hs.27657 KIAA0802 protein 9.41
434061 AW024973 Hs.283675 NPD009 protein 9.40
424572 M19650 Hs.179600 2',3'-cycllc nucleotide 3' phosphodleste 9.40
435937 AA830893 Hs.119769 ESTs 9.35
447818 W79940 Hs.21906 Homo sapiens clone 24670 mRNA sequence 9.34
431374 BE258532 Hs.251871 CTP synthase 9.31 431183 NM 006855 Hs.250696 KDEL (Lys-Asp-Glu-Leu) endoplasmlc retlc 9.30
421535 AB-02359 Hs.105478 phosphoribosylformylglyclnamldine syntha 9.28
407896 D76435 Hs.41154 Zic family member 1 (odd-paired Drosophl 9.28
443715 AI583187 Hs.9700 cyclln E1 9.26
431726 NM 015361 Hs.268053 KIAA0029 protein 9.26
451807 W52854 hypothetical protein FLJ23293 similar to 9.23
438461 AW075485 Hs.286049 phosphoseriπe amlnotransferase 9.20
435854 AJ278120 Hs.4996 putatve aπkyrin-repeat containing prate 9.19
408437 AW957744 Hs.278469 lacrimal praline rich protein 9.18
452576 AB023177 Hs.29900 KIAA0960 protein 9.11
450447 AF212223 Hs.25010 hypothetical protein P15-2 9.08
427051 BE178110 Hs.173374 Homo sapiens cDNA FLJ10500 fis, clone NT 9.06
414368 W70171 Hs.75939 uridlne monophosphate kinase 9.06
446945 AI193115 Hs.16611 tumor protein D52-llke 1 9.05
446873 AI554439 ESTs 9.01
450377 AB033091 KIAA1265 protein 9.00
431707 R21326 Hs.267905 hypothetical protein FLJ10422 9.00
417733 AL048678 Hs.82503 H.saplens mRNA for 3'UTR of unknown prat 8.94
428987 NM 004751 Hs.194710 glucosamlnyl (N-acetyl) transferase 3, m 8.93
433212 BE218049 Hs.121820 ESTs 8.93
448520 AB002367 Hs.21355 doublecortin and CaM kinase-IIke 1 8.91
424800 AL035588 Hs.153203 MyoD family Inhibitor 8.90
451752 AB032997 KIAA1171 protein 8.87
401197 ENSP00000229263*:HSPC213. 8.79
442772 AW503680 Hs.5957 Homo sapiens clone 24416 mRNA sequence 8.79
411800 N39342 Hs.103042 microtubule-assoclated protein 1B 8.79
429973 AI423317 Hs.164680 ESTs 8.75
450937 R49131 Hs.26267 ATP-dependant Interferon response prate! 8.72
418721 NM.002731 Hs.87773 protein kinase, cAMP-dependent, catalyti 8.72
400247 Eos Control 8.71
420153 N22120 Hs.75277 hypothetcal protein FLJ13910 8.68
436895 AF037335 Hs.5338 carbonic anhydrase XII 8.68
457465 AW301344 Hs.122908 DNA replication factor 8.67
441031 AI110684 Hs.7645 fibrlnogen, B beta polypeptide 8.61
419239 AA468183 Hs.184598 Homo sapiens cDNA: FLJ23241 fis, clone C 8.60
427982 NM 016156 Hs.181326 KIAA1073 protein 8.60
415914 AA306033 Hs.78915 GA-bindiπg protein transcription factor, 8.60
422656 AI870435 Hs.1569 LIM homeobox protein 2 8.53
443247 BE614387 Hs.333893 c-Myc target JP01 8.51
410102 AW248508 Hs.279727 ESTs; homologue of PEM-3 [Clona savlgnyl 8.50
401451 NM_004496*:Homo sapiens hepatocyte nu e 8.50
441680 AW444598 Hs.7940 RAP1, GTP-GDP dissociation stimulator 1 8.48
452367 U71207 Hs.29279 eyes absent (Drosophila) homolog 2 8.48
444172 BE147740 ESTs, Moderately similar to I38022 hypot 8.48
414883 AA926960 CDC28 protein kinase 1 8.47
412652 AI801777 ESTs 8.46
426788 U66615 Hs.172280 SWI/SNF related, matrix associated, act 8.45
418827 BE327311 Hs.47166 HT021 8.40
415138 C18356 Hs.295944 tissue factor pathway Inhibitor 2 8.39
453507 AF083217 Hs.33085 WD repeat domain 3 8.36
407944 R34008 Hs.239727 desmocollln 2 8.34
407168 R45175 Hs.117183 ESTs 8.33
419631 AW188117 popeye protein 3 8.31
416000 R82342 Hs.79856 ESTs, Weakly similar to S65657 alpha-1C- 8.29
442426 AI373062 Hs.332938 hypothetical protein MGC5370 8.29
409977 AW805510 Hs.97056 hypothetical protein FLJ21634 8.27
412482 AI499930 Hs.334885 mitochoπdrial GTP binding protein 8.24
429597 NM 003816 Hs.2442 a disintegriπ and metalloprotelnase doma 8.23
428340 AF261088 Hs.154721 aconltase 1, soluble 8.22
436557 W15573 Hs.5027 ESTs, Weakly similar to A47582 B-cell gr 8.20
416602 NM 006159 Hs.79389 Protein kinase C-blndlng protein NELL2 8.14
421305 BE397354 Hs.324830 dlptherla toxin resistance protein requl 8.14
453439 AI572438 Hs.32976 guanine nucleotide binding protein 4 8.14
414761 AU077228 Hs.77256 enhancer of zeste (Drosophila) homolog 2 8.12
441362 BE614410 Hs.23044 RAD51 (S. cerevlslae) homolog (E coli Re 8.12
439924 AI985897 Hs.125293 ESTs 8.11
408576 NM 003542 Hs.46423 H4 hlstone family, member G 8.10
429343 AK000785 Hs.199480 Homo sapiens, Simllarto epsln 3, clone 8.10
417720 AA205625 Hs.208067 ESTs 8.08
426167 AF039023 Hs.167496 RAN binding protein 6 8.06
432426 AW973152 Hs.31050 ESTs 8.06
422956 BE545072 Hs.122579 ECT2 protein (Epithelial cell transform! 8.05
415927 AL120168 Hs.78919 Kell blood group precursor (McLeod pheno 8.03
400409 AF153341 Homo sapiens winged helix/forkhead trans 8.02
419743 AW408762 Hs.5957 Homo sapiens clone 24416 mRNA sequence 8.02
430937 X53463 Hs.2704 glutalhlone peroxidase 2 (gastrolntestin 8.01
417576 AA339449 Hs.82285 phosphorlbosylglycinamlde formyltransfer 8.01
433980 AA137152 Hs.286049 phosphoserine amlnotransferase 8.00
405770 NM_002362:Homo sapiens melanoma antigen, 8.00
434423 NM 006769 Hs.3844 LIM domain only 4 8.00
447414 D82343 Hs.74376 neuroblastoma (nerve tissue) protein 7.99
407748 AL079409 HS.3B176 KIAA0606 protein; SCN Clrcadian Oscillat 7.99
422150 AI867118 calpastatn 7.98
417333 AL157545 Hs.173179 bromodomalπ and PHD finger containing, 3 7.97
416391 AI878927 Hs.79284 mesoderm specific transcript (mouse) horn 7.94
418304 AA215702 gb:zr97g10.r1 NCI.CGAP.GCBI Homo sapiens 7.91 430066 AI929659 Hs.237825 signal recognition particle 72kD 7.90
433862 D86960 Hs.3610 KIAA0205 gene product 7.84
430304 AL122071 Hs.238927 Homo sapiens mRNA; cDNA DKFZp434H1235 (f 7.81
446525 AW967069 Hs.211556 hypothetical protein MGC5487 7.80
414217 AI309298 Hs.279898 Homo sapiens cDNA: FLJ23165 fis, clone L 7.78
438549 BE386801 Hs.21858 trinucleotide repeat containing 3 7.78
457211 AW972565 Hs.32399 ESTs, Weakly simllarto S51797 vasodllat 7.77
413437 BE313164 Hs.75361 gene from NF2/meningloma region of 22q12 7.77
418164 AI761820 Hs.41074 ESTs, Weakly similar to I39294 McLeod sy 7.76
448826 AI580252 Hs.293246 ESTs, Weakly simllarto putative p150 [H 7.74
437271 AL137445 Hs.28846 Homo sapiens mRNA; cDNA DKFZp5660134 (fr 7.71
450325 AI935962 Hs.91973 ESTs 7.69
429276 AF056085 Hs.198612 G protein-coupled receptor 51 7.67
433201 AB040896 Hs.21104 KIAA1463 protein 7.66
420309 AW043637 Hs.21766 ESTs, Weakly simllarto ALU5.HUMAN ALU S 7.66
427581 NM 014788 Hs.179703 KIAA0129 gene product 7.65
424834 AK001432 Hs.153408 Homo sapiens cDNA FLJ10570 fis, clone NT 7.65
447342 AI199268 Hs.19322 Homo sapiens, Similar to RIKEN cDNA 2010 7.65
416783 AA206186 Hs.79889 moπocyte to macrophage dlfferentlaton-a 7.64
420039 NM 004605 Hs.94581 sulfotransferasθ family, cytosolic, 2B, 7.63
442332 AI693251 Hs.8248 Target CAT 7.63
439941 AI392640 Hs.18272 amino acid transporter system A1 7.63
451061 AW291487 Hs.213659 ESTs, Weakly slmilarto KIAA1357 protein 7.62
409757 NM 001898 Hs.123114 cystatln SN 7.62
438523 H66220 Hs.278177 ESTs 7.61
444670 H58373 Hs.332938 hypothetical protein MGC5370 7.61
446771 AA128965 Hs.60679 TATA box binding protein (TBP)-associate 7.61
427944 AA417878 Hs.48401 ESTs, Moderately similar to ALU8.HUMAN A 7.60
447343 AA256641 Hs.236894 ESTs, Highly similar to S02392 alpha-2-m 7.59
418113 AI272141 Hs.83484 SRY (sex determining region Y)-box 4 7.58
407788 BE514982 Hs.38991 S100 calcium-binding protein A2 7.57
408452 AA054683 Hs.192455 ESTs, Weakly slmilarto ALU7.HUMAN ALU S 7.54
428648 AF052728 Hs.188021 potassium voltage-gated channel, subfaml 7.54
448209 AW160489 Hs.20709 tetraspan 5 7.53
432415 T16971 Hs.289014 ESTs, Weakly similar to A43932 mucin 2 p 7.53
430294 AI538226 Hs.32976 guanine nucleotide binding protein 4 7.50
440700 AW952281 Hs.296184 guanine nucleotide binding protein (G pr 7.49
425842 AI587490 Hs.159623 NK-2 (Drosophila) homolog B 7.47
409799 D11928 Hs.76845 phosphoserlne phosphatase-like 7.46
408524 D87942 Hs.46328 fucosyltransferase 2 (secretor status In 7.42
433730 AK002135 Hs.3542 hypothetical protein FLJ 11273 7.41
444783 AK001468 Hs.62180 anlllln (Drosophila Scraps homolog), act 7.39
450378 AW249181 Hs.198899 ESTs, Weakly similar to T19873 hypothet 7.39
452721 AJ269529 Hs.301871 solute carrier family 37 (glycerol-3-pho 7.39
422283 AW411307 Hs.114311 CDC45 (cell division cycle 45, S.cerevis 7.38
409974 BE174106 Hs.225641 hypothetical protein FLJ13171 7.38
426779 AA384577 Hs.93714 ESTs, Weakly slmilarto T00365 hypothet 7.38
424602 AK002055 Hs.151046 hypothetical protein FLJ11193 7.36
431789 H19500 Hs.269222 mltogen-activated protein kinase 4 7.36
435538 AB011540 Hs.4930 low density lipoproteln receptor-related 7.35
437810 BE246399 hypothetical protein 7.35
425843 BE313280 Hs.159627 death associated protein 3 7.34
424544 M88700 Hs.150403 dopa decarboxylase (aromatic L-amino acl 7.33
416426 AA180256 Hs.210473 Homo sapiens cDNA FLJ14872 fis, clone PL 7.32
412715 NM 000947 Hs.74519 primase, polypeptide 2A (58kD) 7.32
420552 AK000492 Hs.98806 hypothetical protein 7.29
409509 AL036923 Hs.322710 ESTs 7.29
439708 AI761369 Hs.59584 hypothetical protein FLJ21144 7.29
420281 AI623693 Hs.323494 Predicted cation efflux pump 7.29
406972 M32053 gb:Human H19 RNA gene, complete eds. 7.28
446595 T57448 Hs.15467 hypothetical protein FLJ20725 7.27
412942 AL120344 Hs.75074 mitogen-activated protein klnase-actvat 7.27
445098 AL050272 Hs.12305 DKFZP566B183 protein 7.26
446006 NM 004403 Hs.13530 deafness, autosomal dominant 5 7.24
412935 BE267045 Hs.75064 tubulln-speclfic chaperone c 7.23
432103 T15803 Hs.272458 protein phosphatase 3 (formerly 2B), cat 7.22
446619 AU076643 Hs.313 secreted phosphoproteln 1 (osteopontin, 7.20
436009 H57130 Hs.120925 ESTs 7.20
445413 AA151342 Hs.12677 CGI-147 protein 7.20
417454 NM 000202 Hs.172458 iduronate 2-sulfatase (Hunter syndrome) 7.19
442445 AA082665 Hs.209561 KIAA1715 protein 7.18
411975 AI916058 Hs.144583 3'UTR of: dead ringer (Drosophlla)-llke 7.18
426501 AW043782 Hs.293616 ESTs 7.18
426759 AI590401 Hs.21213 ESTs 7.17
447644 AW861622 Hs.108646 Homo sapiens cDNA FLJ14934 fis, clone PL 7.16
413654 AA331881 Hs.75454 peroxiredoxln 3 7.16
445893 AI610702 Hs.202613 ESTs, Weakly simllarto TRHY HUMAN TRICH 7.12
407252 AA659037 Hs.163780 ESTs 7.12
423242 AL039402 Hs.125783 DEME-6 protein 7.08
426471 M22440 Hs.170009 transforming growth factor, alpha 7.08
418027 AB037807 Hs.83293 hypothetical protein 7.05
448497 BE613269 Hs.21893 hypothetical protein DKFZp761N0624 7.05
446636 AC002563 Hs.15767 citron (rho-Interactlng, εeriπe/threonln 7.03
416498 U33632 Hs.79351 potassium channel, subfamily K, member 1 7.02
412452 AA215731 suppression of tumorigeniclty 5 7.02
413281 AA861271 Hs.222024 transcription factor BMAL2 6.99 434540 NM 016045 Hs.3945 CGI-107 protein 6.98
445994 NM 004724 Hs.13512 ZW10 (Drosophila) homolog, centromere/kl 6.98
416815 U41514 Hs.80120 UDP-N-acetyl-alpha-D-galactosamIne:polyp 6.97
418338 NM 002522 Hs.84154 neuronal pentraxln 1 6.97
436389 AI811706 Hs.42733 CHMP1.5 protein 6.94
418203 X54942 Hs.83758 CDC28 protein kinase 2 6.93
418863 AL135743 Hs.25566 ESTs, Weakly simllarto 2004399A chromos 6.93
413551 BE242639 Hs.75425 ublqultn associated protein
424505 AA446131 Hs.124918 KIAA1795 protein 6.92
426359 AA376409 Hs.10862 Homo sapiens cDNA: FLJ23313 fis, clone H 6.91
423453 AW450737 Hs.128791 CGI-09 protein 6.91
450256 AA286887 Hs.24724 MFH-ampllfied sequences with leuclne-ric 6.91
443119 AA312264 Hs.7980 hypothetical protein MGC12966
410268 AA316181 Hs.61635 six transmembrane epithelial antgen of
406850 AI624300 Hs.172928 collagen, type I, alpha 1 6.90
409619 AK001015 Hs.55220 BCL2-assoclated athanogene 2 6.88
424381 AA285249 Hs.146329 protein kinase Chk2 (CHEK2) 6.86
431548 AI834273 Hs.9711 novel protein 6.84
409420 Z15008 Hs.54451 lamlnln, gamma 2 (nlceln (100kD), kallni 6.84
453454 AW052006 PRP4/STK/WD splicing factor 6.83
407807 AL031427 Hs.40094 Human DNA sequence from clone 167A19 on 6.82
445863 R12234 Hs.13396 Homo sapiens clone 25028 mRNA sequence 6.80
442069 AW664144 Hs.297007 membrane-bound transcription factor prot 6.78
428771 AB028992 Hs.193143 KIAA1069 protein 6.78
426141 C05886 Hs.293972 ESTs 6.77
445817 NM.003642 Hs.13340 hlstone acetyltransferase 1 6.77
408249 AW271838 Hs.44038 pellino (Drosophila) homolog 2 6.76
438209 AL120659 Hs.6111 aryl-hydrocarbon receptor nuclear transl 6.75
420164 AW339037 Hs.24908 ESTs 6.75
417821 BE245149 Hs.82643 protein tyrosine kinase 9 6.74
432978 AF126743 Hs.279884 DNAJ domain-containing 6.73
428484 AF104032 Hs.184601 solute carrier family 7 (cationic amino 6.73
433409 AI278802 Hs.25661 ESTs 6.73
427286 AW732802 Hs.2132 epidermal growth factor receptor pathway 6.72
431770 BE221880 Hs.268555 5'-3' exoriboπuclease 2 6.72
407635 AW370213 Hs.295232 ESTs, Moderately similar to A46010 X-lin 6.72
410240 AL157424 Hs.61289 synaptojanln 2 6.72
401519 C15000476*:gI|12737279|ref|XP 012163.1| 6.71
409557 BE182896 Hs.3686 ESTs 6.71
445800 AA126419 Hs.32944 Inosltol polyphosphate-4-phosphatase, ty 6.70
415947 U04045 Hs.78934 mutS (E. coil) homolog 2 (colon cancer, 6.70
426125 X87241 Hs.166994 FAT tumor suppressor (Drosophila) homolo 6.70
451418 BE387790 Hs.26369 hypothetical protein FLJ20287 6.69
428698 AA852773 Hs.334838 KIAA1866 protein 6.68
429903 AL134197 Hs.93597 cyclin-dependent kinase 5, regulatory su
433437 U20536 Hs.3280 caspase 6, apoptosis-related cystelne pr 6.66
411945 AL033527 Hs.92137 L-myc-2 protein (MYCL2) 6.65
424140 Z48051 Hs.141308 yelln ollgodendrocyte glycoprotein 6.65
413010 AA393273 Hs.75133 transcrlpton factor 6-like 1 (mltochoπd 6.63
438915 AA280174 Hs.285681 Williams-Beuren syndrome chromosome regl 6.63
410619 BE512730 Hs.65114 keratin 18 6.62
410174 AA306007 Hs.59461 DKFZP434C245 protein 6.62
423250 BE061916 Hs.125849 chromosome 8 open reading frame 2 6.62
409542 AA503020 Hs.36563 hypothetical protein FLJ22418 6.61
448664 AI879317 Hs.334691 splicing factor 3a, subunlt 1 , 120kD 6.61
429332 AF030403 Hs.199263 Ste-20 related kinase 6.61
421778 AA428000 Hs.283072 actπ related protein 2/3 complex, subun 6.60
450800 BE395161 Hs.1390 proteasome (prosome, macropaln) subunlt, 6.57
433556 W56321 Hs.111460 calcium/calmodulin-dependent protein kin 6.55
434263 N34895 Hs.79187 ESTs 6.54
422967 AL117526 Hs.118164 hypothetical protein FLJ 12383 6.54
429183 AB014604 Hs.197955 KIAA0704 protein 6.53
428753 AW939252 Hs.192927 hypothetical protein FLJ20251 6.53
443991 NM 002250 Hs.10082 potassium Intermediate/small conductance 6,53
442092 AW578669 hypothetical protein FLJ12439 6.52
442013 AA506476 Hs.82689 Human DNA sequence from clone RP11-353C1 6.51
414706 AW340125 Hs.76989 KIAA0097 gene product 6.51
434629 AA789081 Hs.4029 glloma-amplifled sequeπce-41 6.50
452259 AA317439 Hs.28707 signal sequence receptor, gamma (traπslo 6.50
428471 X57348 Hs.184510 stratlfin 6.49
407378 AA299264 Hs.57776 ESTs, Moderately similar to I38022 hypot 6.49
416221 BE513171 Hs.79086 mltochondrial ribosomal protein L3 6.49
426716 NM 006379 Hs.171921 sema domain, immunoglobulin domain (Ig), 6.47
442315 AA173992 Hs.7956 ESTs, Moderately similar to ZN91 HUMAN Z 6.47
442571 C06338 Hs.165464 ESTs 6.46
415156 X84908 Hs.78060 phosphorylase kinase, beta 6.45
443180 R15875 Hs.258576 claudln 12 6.45
429413 NM 014058 Hs.201877 DESC1 protein 6.43
417348 AI940507 Hs.318526 hypothetical protein FLJ12661 6.43
407235 D20569 Hs.169407 SAC2 (suppressor of actin mutations 2, y 6.43
419175 AW270037 KIAA0779 protein 6.41
438321 AA576635 Hs.6153 CGI-48 protein 6.41
413582 AW295647 Hs.71331 hypothetical protein MGC5350 6.41
429788 U87791 Hs.221040 HBS1 (S. cerevlslae)-llke 6.40
410418 D31382 Hs.63325 transmembrane protease, serine 4 6.40
410762 AF226053 Hs.66170 HSKM-B protein 6.39 434614 AI249502 Hs.29669 ESTs 6.39
411865 AA248750 Hs.12332 ESTs 6.39
416072 AL110370 Hs.79000 growth associated protein 43 6.39
433345 AI681545 Hs.152982 hypothetical protein FLJ13117 6.38
412507 L36645 Hs.73964 EphA4 6.38
418004 U37519 Hs.87539 aldehyde dehydrogenase 3 family, member 6.37
422309 U79745 Hs.114924 solute carrierfamlly 16 (monocarboxylic 6.36
415339 NM.015156 Hs.78398 KIAA0071 protein 6.36
410340 AW182B33 Hs.112188 hypothetical protein FLJ13149 6.36
411352 NM 002890 Hs.758 RAS p21 protein activator (GTPase actlva 6.35
423739 AA398155 Hs.97600 ESTs 6.35
419135 R61448 Hs.106728 ESTs, Weakly slmilarto KIAA1353 protein 6.33
413450 Z99716 Hs.75372 N-acetylgalactosamlnidase, alpha- 6.33
447484 AA464839 Hs.292566 hypothetical protein FLJ14697 6.33
413063 AL035737 Hs.75184 chitlnase 3-like 1 (cartilage glycoprote 6.33
419641 BE170548 Hs.118190 Homo sapiens cDNA: FLJ21081 fis, clone C 6.32
400297 AI127076 Hs.306201 hypothetical protein DKFZp56401278 6.32
410963 R78824 Hs.44175 KIAA0919 protein 6.32
420234 AW404908 Hs.96038 Ric (Drosophlla)-like, expressed In many 6.31
408405 AK001332 Hs.44672 hypothetical protein FLJ10470 6.30
408331 NM 007240 Hs.44229 dual specificity phosphatase 12 6.30
451336 AI264643 Hs.3610 ESTs 6.29
409327 L41162 Hs.53563 collagen, type IX, alpha 3 6.29
439211 AI890347 Hs.271923 Homo sapiens cDNA: FLJ22785 fis, clone K 6.27
452223 AA425467 Hs.8035 hypothetical protein MGC2827 6.25
429925 NM.000786 Hs.226213 cytochrome P450, 51 (lanosterol 14-alpha 6.24
420942 H03514 Hs.15589 ESTs 6.24
411605 AW006831 ESTs 6.23
436299 AK000767 Hs.5111 hypothetical protein FLJ 20729 6.22
445903 AI347487 Hs.132781 class I cytokine receptor 6.22
425836 AW955696 Hs.90960 ESTs 6.22
431387 AI878854 Hs.252229 v-maf musculoaponeurotlc fibrosarcoma (a 6.21
437296 AA350994 Hs.20281 KIAA1700 6.20
414715 AA587891 Hs.904 amylo-1,6-glucosldase, 4-alpha-glucanotr 6.20
453204 R10799 Hs.191990 ESTs 6.18
438452 AI220911 Hs.288959 hypothetical protein FLJ20920 6.18
434474 AL042936 Hs.211571 holocytochrome c synthase (cytochrome c 6,17
404440 NM_021048:Homo sapiens melanoma antigen, 6.17
430289 AK001952 Hs.238039 hypothetical protein FLJ11090 6.16
426990 AL044315 Hs.173094 Homo sapiens mRNA for IAA1750 protein, 6.15
446494 AA463276 Hs.288906 WW Domain-Containing Gene 6.15
453830 AA534296 Hs.20953 ESTs 6.15
408713 NMJ01248 Hs.47042 ectonudeoside triphosphate diphosphohyd 6.15
423979 AF229181 Hs.136644 CS box-containing WD protein 6.15
412659 AW753865 Hs.74376 olfactomedin related ER localized protel 6.14
417601 NM 014735 Hs.82292 KIAA0215 gene product 6.14
422085 AB018257 Hs.288773 zinc finger protein 294 6.14
417381 AF164142 Hs.82042 solute carrierfamlly 23 (nucleobase tra 6.14
446390 AA233393 Hs.14992 hypothetical protein FLJ11151 6.13
441285 NM 002374 Hs.167 mlcrotubule-assoclated protein 2 6.12
409062 AL157488 Hs.50150 Homo sapiens mRNA; cDNA DKFZp564B182 (fr 6.12
440675 AW005054 Hs.279788 ESTs, Weakly similar to KCC1 HUMAN CALCI 6.11
448072 AI459306 Hs.24908 ESTs 6.10
430387 AW372884 Hs.240770 nuclear cap binding protein subunlt 2, 2 6.10
424036 AA770688 H2A hlstone family, member L 6.10
432908 AI861896 ESTs 6.10
431512 BE270734 Hs.2795 lactate dehydrogenase A 6.09
454293 H49739 Hs.134013 ESTs, Moderately similar to HK61 HUMAN H 6.09
431452 AI073641 Hs.152372 ESTs, Weakly similar to 2109260A B cell 6.09
447197 R36075 gb:yh88b01 ,s1 Soares placenta Nb2HP Homo 6.08
427157 U51166 Hs.173824 thymlne-DNA glycosylase 6.08
422725 AA315703 Hs.199993 ESTs, Weakly slmilarto ALUB.HUMAN llll 6.07
436860 H12751 Hs.5327 PR01914 protein 6.06
426108 AA622037 Hs.166468 programmed cell death 5 6.06
419298 AA853479 Hs.89890 pyruvate carboxylase 6.05
443695 AW204099 ESTs, Weakly similar to AF1267801 retin 6.05
438146 Z36842 Hs.57548 ESTs 6.05
445786 AW629819 Hs.144502 hypothetical protein FLJ22055 6.05
442108 AW452649 Hs.166314 ESTs 6.04
432374 W68815 Hs.301885 Homo sapiens cDNA FLJ11346 fis, clone PL 6.04
414320 U13616 Hs.75893 aπkyrin 3, node of Ranvler (ankyrin G) 6.03
437330 AL353944 Hs.50115 Homo sapiens mRNA; cDNA DKFZp761J1112 (f 6.03
447397 BE247676 Hs.18442 E-1 enzyme 6.03
458814 AI498957 Hs.170861 ESTs, Weakly simllarto Z195.HUMAN ZINC 6.03
429429 AA829725 Hs.334437 hypothetical protein MGC4248 6.03
402736 NM 024852:Homo sapiens hypothetcal prot 6.03
450353 AI244661 Hs.103296 ESTs, Weakly similar to S65657 alpha-IG- 6.02
453078 AF053551 Hs.31584 metaxln 2 6.02
441659 BE564162 Hs.250820 hypothetical protein FLJ14827 6.01
439696 W95298 Hs.171882 ESTs 6.01
417878 U90916 Hs.82845 Homo sapiens cDNA: FLJ21930 fis, clone H 6.00
420956 AA351584 Hs.100543 Homo sapiens clone 24505 mRNA sequence 5.99
445652 AL117473 Hs.13036 DKFZP727A071 protein 5.98
430300 U60805 Hs.238648 oncostatin M receptor 5.98
430935 AW072916 zinc finger protein 131 (clone pHZ-10) 5.98
415276 U88666 Hs.78353 SFRS protein kinase 2 5.97 448369 AW268962 Hs.111335 ESTs 5.97
431049 AA846576 Hs.103267 hypothetical protein FLJ22548 similar to 5.96
417233 W25005 Hs.24395 small Inducible cytokine subfamily B (Cy 5.96
446882 H13878 Hs.165195 Homo sapiens cDNA FLJ14237 fis, clone NT 5.96
422912 AW405973 Hs.11637 ESTs 5.96
423134 AJ012582 Hs.124161 hyperpoIarizaUon activated cyclic nude 5.96
429505 AW820035 Hs.278679 a dislntegrin and metalloprotelnase doma 5.95
441623 AA315805 desmoglein 2 5.94
409407 AW967370 Hs.342655 Homo sapiens cDNA FLJ132B9 fis, clone OV 5.94
408089 H59799 Hs.42644 thioredoxin-like 5.94
407110 AA018042 Hs.252085 Prader-Wllli/Angelman syndrome-5 5.93
452466 N84635 Hs.29664 hypothetical protein DKFZp564B052 5.93
450314 AA574309 Hs.283402 TCReta 5.92
452620 AA436504 Hs.119286 ESTs 5,92
440325 NM 003812 Hs.7164 a dislntegrin and metalloprotelnase doma 5.91
407604 AW191962 collagen, type VIII, alpha 2 5.91
449103 T24968 Hs.23038 HSPC071 protein 5.91
416990 AF124145 Hs.80731 autocrlne motllty factor receptor 5.90
414844 AA296874 Hs.77494 deoxyguanosine kinase 5.90
430454 AW469011 Hs.105635 ESTs 5.90
437915 AI637993 Hs.202312 Homo sapiens clone N11 NTera2D1 teratoca 5.89
448939 BE267795 Hs.22595 hypothetical protein FLJ10637 5.88
426216 N77630 Hs.13895 Homo sapiens cD A FLJ 11654 fis, clone HE 5.88
432329 NM 002962 Hs.2960 S100 calcium-binding protein A5 5.88
452994 AW962597 Hs.31305 KIAA1547 protein 5.88
441790 AW294909 Hs.132208 ESTs 5.86
444099 DB7432 Hs.10315 solute carrierfamlly 7 (cationic amino 5.86
427658 H61387 Hs.30868 nogo receptor 5.86
401866 Target Exon 5.86
438510 AL080220 Hs.6285 DKFZP586P0123 protein 5.85
446813 AA971436 Hs.16218 KIAA0903 protein 5.85
458748 AI381530 gb:te76d07.x1 Soares NFL T GBC.S1 Homos 5.85
425523 AB007948 Hs.158244 KIAA0479 protein 5.85
428832 AA578229 Hs.324239 ESTs, Moderately similar to ZN91.HUMAN Z 5.85
431846 BE019924 Hs.271580 uroplakln 1B 5.85
422363 T55979 Hs.115474 replication factorC (activator 1) 3 (38 5.84
418322 AA284166 Hs.84113 cyclln-dependent kinase Inhibitor 3 (CDK 5.84
426158 NM 001982 Hs.199067 v-erb-b2 avlan erythroblastlc leukemia v 5.83
448122 AW665656 Hs.173187 ESTs 5.83
436045 AB037723 Hs.5028 DKFZP564O0423 protein 5.83
442045 C05768 Hs.8078 Homo sapiens clone FBD3 Cri-du-chat crlt 5.82
409129 AW296699 Hs.103521 serine arglnlne-rich pre-mRNA splicing f 5.82
443162 T49951 Hs.9029 DKFZP434G032 protein 5.80
448690 AK001304 Hs.21771 Wolf-Hlrschhom syndrome candidate 2 5.80
433017 Y15067 Hs.279914 zinc finger protein 232 5.79
430168 AW968343 Hs.145582 DKFZP434I1735 protein 5.79
449444 AW818436 solute carrierfamlly 16 (monocarboxylic 5.79
435798 BE395289 Hs.12720 elF4E-transporter 5.78
408411 C15118 Hs.322482 hypothetical protein DKFZp566J2046 5.78
416179 R19015 Hs.79067 MAD (mothers against decapeπtapleglc, Dr 5.77
453902 BE502341 Hs.3402 ESTs 5.77
422939 AW394055 Hs.98427 ESTs, Weakly similar to I38022 hypothet 5.77
434094 AA305599 Hs.238205 hypothetical protein PRO2013 5.76
437834 AA769294 gb:nz36g03.s1 NCI.CGAP.GCBI Homo sapiens 5.76
450516 AA902656 Hs.21943 NIF3 (Nggl Interacting factor 3, S.pombe 5.76
440043 BE277457 Hs.30661 hypothetical protein MGC4606 5.75
418816 T29621 Hs.88778 carbonyl reductase 1 5.74
437672 AW748265 Hs.5741 flavohemoproteiπ b57 5.74
433029 NM 014322 Hs.279926 opsln 3 (encephalopsln) 5.74
413585 Al 133452 Hs.75431 flbrinogen, gamma polypeptide 5.73
413435 X51405 Hs.75360 carboxypeptdase E 5.73
430044 AA464510 Hs.152812 ESTs 5.73
439559 AW364675 Hs.173921 ESTs, Weakly slmilarto 2109260A B cell 5.73
424130 AL050136 Hs.140945 Homo sapiens mRNA; cDNA DKFZp586L141 (fr 5.73
441962 AW972542 Hs.289008 Homo sapiens cDNA: FLJ21814 fis, clone H 5.71
433002 AF048730 Hs.279906 cyclin T1 5.71
425463 AK000740 Hs.157986 molybdenum cofactorsulfurase 5.71
432728 NM 006979 Hs.278721 HLA class II region expressed gene KE4 5.71
451351 AW058261 Hs.321435 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 5.70
404568 NM_022071*:Homo sapiens hypothetical pro 5.70
419926 AW900992 Hs.93796 DKFZP586D2223 protein 5.70
428654 NM 012091 Hs.188661 adenoslπe deaminase, tRNA-speclfic 1 5.69
440351 AF030933 Hs.7179 RAD1 (S. pombe) homolog 5.68
448479 H96115 Hs.21293 UDP-N-acteylglucosamlne pyrophosphorylas 5.67
456141 AI751357 Hs.288741 Homo sapiens cDNA: FLJ22256 fis, clone H 5.66
419539 AF070590 Hs.90869 Homo sapiens clones 24622 and 24623 mRNA 5.65
409717 AW452871 Hs.56043 CGI-115 protein 5.64
408633 AW963372 Hs.46677 PRO2000 protein 5.64
409235 AA188827 Hs.7988 ESTs, Weakly similar to 138022 hypothet 5.63
439580 AF086401 Hs.293847 ESTs, Moderately similar to S65657 alpha 5.63
453935 AI633770 Hs.42572 ESTs 5.63
420187 AK001714 Hs.95744 hypothetcal protein similar to ankyrln 5.63
453271 AA903424 Hs.6786 ESTs 5.63
424364 AW383226 Hs.163834 ESTs, Weakly slmilarto G01763 atrophin- 5.62
415791 H09366 Hs.78853 uracll-DNAglycosylase 5.62
415701 NM 003878 Hs.78619 gamma-glutamyl hydrolase (coπjugase, fol 5.62 424723 BE409813 Hs.152337 protein arglnlπe N-methyltraπsferase 3(h 5.61
407930 AA045847 Hs.188361 Homo sapiens cDNA FLJ12807 fis, clone NT 5.60
408670 AF160967 Hs.46784 potassium large conductance calclum-acti 5.60
447495 AW401864 Hs.18720 programmed cell death 8 (apoptosls-induc 5.59
426318 AA375125 Hs.147112 Homo sapiens cDNA: FLJ22322 fis, clone H 5.59
431448 AL137517 Hs.306201 hypothetical protein DKFZp56401278 5.58
452461 N78223 Hs.108106 transcription factor 5.58
430598 AK001764 Hs.247112 hypothetical protein FLJ10902 5.56
414343 AL036166 Hs.75914 coated vesicle membrane protein 5.56
433627 AF078866 Hs.284296 Homo sapiens cDNA: FLJ22993 fis, clone K 5.56
448045 AJ297436 Hs.20166 prostate stem cell antgen 5.55
428428 AL037544 Hs.184298 cyclln-dependent kinase 7 (homolog of Xe 5.55
416883 AW14012B Hs.184902 ESTs 5.55
420126 NM 016255 Hs.95260 Autosomal Highly Conserved Protein 5.55
408784 AW971350 Hs.63386 ESTs 5.55
417059 AL037672 Hs.81071 extracellular matrix protein 1 5.55
416782 L35035 Hs.79886 ribose 5-phosphate Isomerase A (ribose 5 5.53
442366 AA115629 Hs.118531 ESTs 5.53
429609 AF002246 Hs.210863 cell adhesion molecule with homology to 5.53
414612 BE274552 Hs.76578 protein Inhibitor of activated STAT3 5.53
419354 M62839 Hs.1252 apollpoprotein H (beta-2-glycoproteln I) 5.52
426252 BE176980 Hs.28917 ESTs 5.51
437435 AA249439 Hs.27027 hypothetical protein DKFZp762H1311 5.51
435770 AA699991 Hs.348162 gb:z!69a09.s1 Soares.fetaljiver.spleen. 5.51
420230 AL034344 Hs.284186 forkhead boxCI 5.51
430539 AK001489 ADP-ribosylatlon factor-like 1 5.50
431899 AA521381 Hs.187726 ESTs 5.49
455510 AA422029 Hs.143640 ESTs, Weakly simllarto hyperpolarizatlo 5.49
451622 AW139587 Hs.30579 Homo sapiens cDNA: FLJ23070 fis, clone L 5.49
448789 BE539108 Hs.22051 hypothetical protein MGC15548 5.49
434067 H18913 Hs.124023 Homo sapiens cDNA FLJ14218 fis, clone NT 5.48
429687 AI675749 Hs.211608 nucleoporin 153kD 5.48
428816 AA004986 Hs.193852 ATP-blndlπg cassette, sub-family C (CFTR 5.47
442767 AI017208 Hs.131149 ESTs 5.45
451259 NM 006052 Hs.26146 Down syndrome critical region gene 3 5.45
453985 N44545 Hs.251865 ESTs 5.45
452167 N75238 Hs.13075 Homo sapiens cDNA: FLJ23013 fis, clone L 5.45
414341 D80004 Hs.75909 KIAA0182 protein 5.44
452518 AA280722 Hs.24758 ESTs, Weakly similar to I38022 hypothet 5.44
438182 AW342140 Hs.182545 ESTs, Weakly similar to ALU1.HUMAN ALU S 5.43
430057 AW450303 Hs.2534 bone morphogβnetc protein receptor, typ 5.43
433675 AW977653 Hs.75319 ribonucleotlde reductase M2 polypeptide 5.43
413476 U25849 Hs.75393 a d phosphatase 1, soluble 5.43
430508 AI015435 Hs.104637 ESTs 5.42
437204 AL110216 ESTs, Weakly simllarto 155214 salivary 5.42
430335 D80007 Hs.239499 KIAA0185 protein 5.41
446825 BE266822 Hs.344097 filamln A, alpha (actn-blnding protein- 5.41
409190 AU076536 Hs.50984 sarcoma amplified sequence 5.40
440282 BE262386 clones 23667 and 23775 zinc finger prote 5.40
426860 U04953 Hs.172801 Isoleuclne-tRNA synthetase 5.40
414987 AA524394 Hs.294022 hypothetical protein FLJ14950 5.39
451101 N22587 Hs.270134 Homo sapiens cDNA FLJ11752 fis, clone HE 5.38
422611 AA158177 Hs.118722 fucosyltransferase 8 (alpha (1,6) fucosy 5.37
440193 AW902312 Hs.7037 Homo sapiens clone 24923 mRNA sequence 5.37
451593 AF151879 Hs.26706 CGI-121 protein 5.37
429503 AA394183 Hs.204166 ESTs 5.37
427087 BE073913 Hs.173515 uncharacterized hypothalamus protein HTO 5.36
401403 Target Exon 5.36
417731 D26018 Hs.82502 polymerase (DNA directed), delta 3 5.35
444735 BE019923 Hs.243122 hypothetical protein FLJ13057 similar to 5.35
417615 BE548641 Hs.82314 hypoxanthine phosphoribosyltransferase 1 5.35
416111 AA033813 Hs.79018 chromatn assembly factor 1, subunlt A ( 5.34
408831 AF090114 Hs.48433 endocrine regulator 5.34
413333 M74028 Hs.75297 fibroblast growth factor 1 (acidic) 5.34
416959 D28459 Hs.80612 ublqultln-conjugatng enzyme E2A (RAD6 h 5.33
457001 J03258 Hs.2062 vitamin D (1,25- dihydroxyvitamin D3) re 5.32
450251 BE080483 gb:QV1-BT0630-280200-086-a05 BT0630 Homo 5.32
436961 AW375974 Hs.156704 ESTs 5.30
452092 BE245374 Hs.27842 hypothetical protein FLJ11210 5.30
439680 AW245741 Hs.58461 ESTs, Weakly slmilarto A35659 krueppel- 5.30
441865 AA384726 Hs.5722 hypothetlcal protein FLJ23316 5.30
443015 R33261 Hs.6614 ESTs, Weakly slmilarto A43932 mucin 2 p 5.29
433388 AI432672 Hs.288539 hypothetical protein FLJ22191 5.29
421180 BE410992 Hs.258730 heme-regulated Initation factor 2-alpha 5.29
410935 BE067395 Hs.66881 dyneln, cytoplasmlc, Intermediate polype 5.28
427846 AW499770 Hs.180948 KIAA0729 protein 5.28
437659 AB007944 Hs.5737 KIAA0475 gene product 5.28
442711 AF151073 Hs.8645 hypothetical protein 5.28
431197 AL038596 Hs.250745 polymerase (RNA) III (DNA directed) (62k 5.27
451945 BE504055 Hs.211420 ESTs 5,27
402812 NM_004930*:Homo sapiens capping protein 5.26
402802 NM_001397:Homo sapiens eπdothelln conver 5.26
428417 AK001699 Hs.184227 F-box only protein 21 5.26
451468 AW503398 Hs.293663 ESTs, Moderately similar to I38022 hypot 5.25
422975 AA347720 Hs.122669 KIAA0264 protein 5,25
424395 AA165082 Hs.146388 mlcrotubule-assoclated protein 7 5.24 434938 AW500718 Hs.8115 Homo sapiens, clone MGC:16169, mRNA, com 5.24
458621 AI221741 Hs.117777 ESTs 5.24
449209 BE616830 Hs.294145 ESTs 5.24
443837 AI984625 Hs.9884 spindle pole body protein 5.23
421977 W94197 Hs.110165 ribosomal protein L26 homolog 5.23
433561 BE540937 Hs.20104 hypothetical protein FLJ00052 5.22
448555 AI536697 Hs.159863 ESTs 5.22
428479 Y00272 Hs.334562 cell division cycle 2, G1 to S and G2 to 5.22
422072 AB018255 Hs.111138 KIAA0712 gene product 5.22
418250 U29926 Hs.83918 adenoslne monophosphate dea lπase (isofo 5.22
431771 AW239175 Hs.2853 poly(rC)-binding protein 1 5.22
410079 U94362 Hs.58589 glycogenlπ 2 5.22
449810 AB008681 Hs.23994 activin A receptor, type IIB 5.21
427735 AA916785 Hs.180610 splicing factor proliπe/glutamlπe rich ( 5.21
424179 F30712 Hs.334573 Homo sapiens, clone IMAGE:42B5740, mRNA 5.20
448275 BE514434 Hs.20830 kinesln-llke 2 5.20
421875 AA299607 Hs.98969 ESTs 5.20
448770 AA326683 Hs.21992 likely ortholog of mouse variant polyade 5.19
418248 NM 005000 Hs.83916 NM 005000*:Homo sapiens NADH dehydrogena 5.19
444563 N57057 Hs.284163 ANKHZN protein 5.19
441181 AA416925 pept ylprolyl isomerase (cyclophllin)-l 5.19
415025 AW207091 Hs.72307 ESTs 5.19
453496 AA442103 Hs.33084 solute carrierfamlly 2 (facilitated glu 5.18
400205 NM_006265*:Homo sapiens RAD21 (S. pombe) 5.18
447881 BE620886 GCN1 (general control of amlno-acld synt 5.17
450052 AI681298 Hs.236524 ESTs 5.15
452221 C21322 Hs.288057 hypothetical protein FLJ22242 5.15
404996 Target Exon 5.15
432375 BE536069 Hs.2962 S100 calcium-binding protein P 5.15
423493 AI815965 Hs.129683 ublquitin-conjugatπg enzyme E2D 1 (homo 5.14
452110 T47667 Hs.28005 Homo sapiens cDNA FLJ 11309 fis, clone PL 5.14
407804 AF228603 Hs.39957 pleckstriπ 2 (mouse) homolog 5.14
437258 AL041243 Hs.174104 ESTs 5.14
447064 AB002350 Hs.17262 KIAA0352 gene product 5.14
448439 BE613082 Hs.28229 ARG99 protein 5.14
420344 BE463721 Hs.97101 putative G protein-coupled receptor 5.13
420440 NM 002407 Hs.97644 mammaglobln 2 5.13
422616 BE300330 Hs.118725 selenophosphate syntietase 2 5.13
427254 AL121523 Hs.97774 ESTs 5.12
451321 AW593532 Hs.124135 Homo sapiens cDNA FLJ13051 fis, clone NT 5.12
449048 Z45051 Hs.22920 slmilarto S68401 (cattle) glucose Indue 5.12
428781 AF164799 Hs.193384 putatative 28 kDa protein 5.12
426230 AA367019 Hs.241395 protease, serine, 1 (trypsin 1) 5.11
425649 U30930 Hs.158540 UDP glycosyltransferase 8 (UDP-galactose 5.11
440100 BE382685 Hs.158549 ESTs, Weakly simllarto T2D3 HUMAN TRANS 5.11
433037 NM 014158 Hs.279938 HSPC067 protein 5.10
441224 AU076964 Hs.7753 calumeniπ 5.10
420734 AW972872 Hs.293736 ESTs 5.10
419355 AA428520 Hs.90061 progesterone binding protein 5.09
425673 R70318 Hs.339730 ESTs 5.09
400583 Target Exon 5.09
452737 AK001680 Hs.30488 DKFZP434F091 protein 5.09
421928 AF013758 Hs.109643 polyadenylate binding proteln-interactn 5.09
439609 AW971945 Hs.293236 ESTs 5.08
400277 Eos Control 5.08
448100 AV655272 Hs.20252 novel Ras family protein 5.07
445309 AL157474 Hs.12504 likely ortholog of mouse Arkadla 5.07
428180 AI129767 Hs.182874 guanine nucleotide binding protein (G pr 5.07
412574 BE410731 Hs.74050 folllcular lymphoma variant translocatlo 5.07
444385 BE278964 Hs.11085 CGI-111 protein 5.06
422095 AI868872 Hs.282804 hypothetical protein FLJ22704 5.06
435905 AW997484 Hs.5003 KIAA0456 protein 5.06
417378 R57256 Hs.82037 TATA box binding protein (TBP)-associate 5.06
453295 W56819 ESTs, Weakly similar to I38022 hypothet 5.06
422938 NM 001809 Hs.1594 centromere protein A (17kD) 5.06
408363 NM 003389 Hs.44396 coronln, actin-blndlng protein, 2A 5.06
424438 AA340724 Hs.271912 ESTs, Weakly similar to A42442 Integrin 5.05
435468 AW362803 Hs.166271 ESTs 5.05
402053 C11001722*:gI|11436283|ref|XP 006959.1| 5.04
419341 N71463 Hs.118888 ESTs, Weakly similar to ALU1.HUMAN ALU S 5.04
400880 NM 00611*:Homo sapiens CD59 antgen p18 5.04
428728 NM 016625 Hs.191381 hypothetical protein 5.04
429048 AI372949 Hs.44241 Homo sapiens cDNA: FLJ21447 fis, clone C 5.04
428690 AI948490 Hs.98765 ESTs 5.04
452256 AK000933 Hs.28661 Homo sapiens cDNA FLJ10071 (Is, clone HE 5.04
445495 BE622641 Hs.38489 ESTs, Weakly similar to I38022 hypothet 5.03
423554 M90516 Hs.1674 glutamIπe-fructose-6-phosphate transamln 5.03
436643 AA757626 Hs.10941 ESTs, Weakly simllarto IPP1.HUMAN PROTE 5.03
420522 AW957137 Hs.98541 hypothetical protein 5.03
436995 AI160015 Hs.125489 ESTs 5.02
421077 AK0O0O61 Hs.101590 hypothetical protein 5.02
411412 AJ001388 Hs.69997 zinc finger protein 238 5.02
419551 AW582256 Hs.91011 anterior gradient 2 (Xenepus laevls) horn 5.02
413687 AI522318 Hs.103819 ESTs 5.02
442313 BE388898 Hs.8215 hypothetical protein FLJ11307 5.01
408705 AA312135 Hs.46967 HSPC034 protein 5.00 440660 AI300101 Hs.131886 Homo sapiens cDNA: FLJ22113 fis, clone H 5.00
448920 AW408009 Hs.22580 alkylglycerone phosphate synthase 5.00
439574 AI469788 ESTs 5.00
437739 AW579216 Hs.264610 ESTs, Moderately similar to Ibd1 [H.sapl 4.99
414405 AI362533 KIAA0306 protein 4.99
418661 NM 001949 Hs.1189 E2F transcription factor 3 4.99
429966 BE081342 Hs.283037 HSPC039 protein 4.98
408000 L11690 Hs.198689 bullous pemphlgoid antigen 1 (230/240kD) 4.98
427209 H06509 Hs.92423 KIAA1566 protein 4.98
421227 R78581 Hs.266308 mosaic serine protease 4.98
451989 AF169797 Hs.27413 adaptor protein containing pH domain, PT 4.98
442328 AI952430 Hs.150614 ESTs, Weakly similar to ALU4.HUMAN ALU S 4.97
422385 BE549407 Hs.115823 ribonuclease P, 40kD subunlt 4.97
429617 X89984 Hs.211563 B-cell CLUIymphoma 7A 4.97
434369 AI650363 Hs.116462 ESTs 4.97
452144 AA032197 Hs.102558 Homo sapiens, clone MGC:5352, mRNA, comp 4.97
436823 AW749865 Hs.117077 ESTs, Weakly simllarto I38022 hypotheti 4.97
451380 H09280 Hs.13234 ESTs 4.96
427083 NM 006363 Hs.173497 Sec23 (S. cerevlslae) homolog B 4.96
418888 AU076801 Hs.89436 cadherin 17, LI cadherin (llver-lntestin 4.95
408771 AW732573 Hs.47584 potassium voltage-gated channel, delayed 4.95
446572 AV659151 Hs.282961 ESTs 4.95
449145 AI632122 Hs.198408 ESTs 4.95
433819 AW511097 Hs.112765 ESTs 4.95
424905 NM 002497 Hs.153704 NIMA (never In mitosis gene a)-related k 4.95
424163 NM 007071 Hs.142245 HERV-H LTR-associating 3 4.94
436865 AW880358 Hs.339808 hypothetical protein FLJ10120 4.94
449437 AI702038 Hs.100057 Homo sapiens cDNA: FLJ22902 fis, clone K 4.94
415558 AA885143 Hs.125719 ESTs 4.94
425683 AB037813 Hs.159200 hypothetical protein DKFZp762K222 4.94
453891 AB037751 Hs.36353 Homo sapiens mRNA full length Insert cDN 4.93
438613 C05569 Hs.243122 hypothetical protein FLJ13057 simllarto 4.93
402408 NM 030920*:Homo sapiens hypothetical pro 4.93
428829 R14050 Hs.194051 Homo sapiens mRNA; cDNA DKFZp566B213 (fr 4.93
418699 BE539639 Hs.173030 ESTs, Weakly slmilarto ALU8.HUMAN ALU S 4.92
422576 BE548555 Hs.118554 CGI-83 protein 4.92
415068 Z19448 Hs.131887 ESTs, Weakly slmilarto T24396 hypothet 4.92
410275 U85658 Hs.61796 transcripton factor AP-2 gamma (actlvat 4.92
432540 AI821517 Hs.105866 ESTs 4.92
422168 AA586894 Hs.112408 S100 calcium-binding protein A7 (psorias 4.92
411704 AI499220 Hs.71573 hypothetical protein FLJ10074 4.91
418803 U50079 Hs.88556 hlstone deacetylase 1 4.90
401747 Homo sapiens keratin 17 (KRT17) 4.90
437387 AI198874 Hs.28847 AD026 protein 4.90
433929 AI375499 Hs.27379 ESTs 4.90
411251 R19774 Hs.22835 HHGP protein 4.90
422567 AF111178 Hs.118407 glypicaπ 6 4.89
424956 AW198103 Hs.18724 ESTs, Weakly slmilarto granule cell mar 4.89
414051 BE244127 gb:TCBAP1E0661 Pedlatric pre-Bcell acut 4.89
447083 AI472124 Hs.157757 ESTs 4.89
456977 AKO0O252 Hs.169758 hypothetical protein FLJ20245 4.88
446795 AI797713 Hs.156471 ESTs 4.88
421515 Y11339 Hs.105352 GalNAc alpha-2, 6-slalyltransferase I, I 4.88
438705 AI049624 Hs.283390 ESTs, Weakly slmilarto 2109260A B cell 4.88
441553 AA281219 Hs.121296 ESTs 4.87
417715 AW969587 Hs.86366 ESTs 4.87
442229 AI885776 Hs.8164 Mulibrey nanism 4.87
436797 AA731491 Hs.334477 hypothetical protein MGC14879 4.87
442739 NM 007274 Hs.8679 cytosolic acyl coenzyme A thloesterhydr 4.87
407813 AL120247 Hs.40109 KIAA0872 protein 4.87
457819 AA057484 Hs.35406 FLJ20522 Hypothetical protein FLJ20522 4.86
430291 AV660345 Hs.238126 CGI-49 protein 4.86
430396 D49742 Hs.241363 hyaluronan-blndlng protein 2 4.86
428330 L22524 Hs.2256 matrix metalloprotelnase 7 (matrilysln, 4.85
427719 AI393122 Hs.134726 ESTs 4.85
442660 AW138174 Hs.130651 ESTs 4.85
435858 AF254260 Hs.283009 tuftellπ 1 4.84
443179 AI928402 Hs.6933 hypothetical protein FLJ12684 4.84
414591 AI888490 Hs.55902 ESTs, Weakly slmilarto ALU8.HUMAN ALU S 4.84
438459 T49300 Hs.35304 Homo sapiens cDNA FLJ13655 fis, clone PL 4.84
409262 AK000631 Hs.52256 hypothetical protein FLJ20624 4.84
407198 H91679 gb:yv04a07.s1 Soares fetal liver spleen 4.84
450737 AW007152 Hs.63325 transmembrane protease, serine 4 4.84
421202 AF193339 Hs.102506 eukaryotc translation Initiation factor 4.83
419586 AI088485 Hs.144759 ESTs, Weakly simllarto I38022 hypothet 4.83
452459 AI356895 Hs.49359 hypothetical protein D FZp547E052 4.83
413429 BE139117 Hs.278881 ESTs 4.83
443426 AF098158 Hs.9329 chromosome 20 open reading frame 1 4.82
413431 AW24642B Hs.75355 ublqultn-conjugatng enzyme E2N (homolo 4.82
427832 AF038362 Hs.180930 TBP-assoclated factor 172 4.82
430000 AW205931 Hs.99598 hypothetical protein MGC5338 4.80
408296 AL117452 Hs.44155 DKFZP586G1517 protein 4.80
447444 AK000318 Hs.18616 hypothetical protein FLJ20311 4.80
425387 AB037864 Hs.156051 KIAA1443 protein 4.80
447514 AI809314 Hs.208501 ESTs, Weakly slmilarto B34087 hypothet 4.80
430333 S70114 Hs.239489 TIA1 cytotoxic granule-associated RNA-bl 4.79 435092 AL137310 Hs.4749 Homo sapiens mRNA; cDNA DKFZp761E13121 ( 4.79
412537 AL031778 nuclear transcription factor Y, alpha 4.79
407204 R41933 Hs.140237 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 4.79
417366 BE185289 Hs.1076 small proline-rich protein 1B (comlfln) 4.78
411387 AW842339 Hs.130815 hypothetical protein FLJ21870 4.78
422244 Y08890 Hs.113503 karyopherin (importlπ) beta 3 4.78
448186 AA262105 Hs.4094 Homo sapiens cDNA FLJ14208 fis, done NT 4.78
422420 U03398 Hs.1524 tumor necrosis factor (ligand) superfami 4.78
421898 AA259011 Hs.109268 hypothetical protein FLJ12552 4.78
408349 BE546947 Hs.44276 homeo box C10 4.78
445892 AV655500 Hs.93961 Homo sapiens mRNA; cDNA DKFZp667D095 (fr 4.78
414108 AI267592 Hs.75761 SFRS protein kinase 1 4.78
442961 BE614474 F-box only protein 22 4.77
441024 AW081530 Hs.268231 ESTs 4.77
448552 AW973653 Hs.20104 hypothetical protein FLJ00052 4.77
424197 AF096834 Hs.142989 germ cell specific Y-box binding protein 4.77
414222 AL135173 Hs.878 sorbitol dehydrogenase 4.76
425769 U72513 Hs.159486 Human RPL13-2 pseudogene mRNA, complete 4.76
425424 NM 004954 Hs.157199 ELKL motif kinase 4.75
426699 AA383337 Hs.121269 ESTs 4.75
424085 NM 002914 Hs.139226 replication factor C (activator 1) 2 (40 4.75
438869 AF075009 gb:Homo sapiens full length Insert cDNA 4.75
451027 AW519204 Hs.40808 Homo sapiens, Similar to RIKEN cDNA 2810 4.74
422684 BE561617 Hs.119192 H2A hlstone family, member Z 4.74
403485 C3001813*:gi|12737279|ref|XP_012163.1| k 4.74
447334 AA515032 Hs.91109 ESTs 4.74
441989 AA306207 Hs.286241 protein kinase, cAMP-dependent, regulato 4.74
432673 AB028859 Hs.278605 DnaJ (Hsp40) homolog, subfamily B, me be 4.73
448362 AA641767 Hs.21015 hypothetical protein DKFZp564L0864 simil 4.73
453199 AI336266 Hs.32353 mltogen-actlvated protein kinase kinase 4.73
450149 AW969781 Hs.132863 Zic family member 2 (odd-paired Drosophl 4.73
419502 AU076704 flbrinogen, A alpha polypeptide 4.72
442787 W93048 Hs.250723 hypothetical protein MGC2747 4.72
447764 NM 003776 Hs.19500 nuclear localization signal deleted In v 4.72
425118 AU076611 Hs.154672 methylene tetrahydrofolate dehydrogenase 4.71
438714 AA814859 ESTs 4.71
409463 AI458165 Hs.17296 hypothetical protein MGC2376 4.71
429610 AB024937 Hs.211092 LUNX protein; PLUNC (palate lung and πas 4.70
411031 W37943 Hs.34892 KIAA1323 protein 4.70
409445 AW341217 Hs.14139 ESTs, Weakly simllarto JC5314 CDC28fcdc 4.70
446019 AI362520 hlstone deacetylase 3 4.70
440074 AA863045 Hs.10669 ESTs, Weakly slmilarto T00050 hypothet 4.70
415989 AI267700 ESTs 4.70
415992 C05837 Hs.145807 hypothetical protein FLJ 13593 4.70
439772 AL365406 Hs.10268 Homo sapiens mRNA full length Insert cDN 4.69
414462 BE622743 Hs.301064 arfaptin 1 4.69
433626 AF078859 Hs.86347 hypothetical protein 4.69
430512 AF182294 Hs.241578 U6 snRNA-assoclated Sm-Ilke protein LSmB 4.68
446269 AW263155 Hs.14559 hypothetical protein FLJ10540 4.68
412828 AL133396 Hs.74621 prion protein (p27-30) (Creutzfeld-Jakob 4.68
409342 AU077058 Hs.54089 BRCA1 associated RING domain 1 4.68
407907 AI752235 Hs.41270 procollagen-lyslne, 2-oxoglutarate 5-dlo 4.68
416586 D44643 Hs.14144 secreted modular calcium-binding protein 4.67
442592 BE566623 Hs.29899 ESTs, Weakly slmilarto G02075 transcrip 4.67
432378 AI493046 Hs.146133 ESTs 4.67
423551 AA327598 Hs.89633 ESTs 4.67
453753 BE252983 Hs.35086 ublquitin specific protease 1 4.67
452834 AI638627 Hs.105685 KIAA1688 protein 4.66
445733 BE295568 Hs.13225 UDP-Gal:betaGlcNAc beta 1,4- galactosylt 4.66
430027 AB023197 Hs.227743 KIAA0980 protein 4.65
403817 NM.015271:Homo sapiens tripartite motlf- 4.65
453742 AB037744 Hs.34892 KIAA1323 protein 4.65
417665 AW852858 Hs.22862 ESTs 4.65
412970 AB026436 Hs.177534 dual specificity phosphatase 10 4.65
441377 BE218239 Hs.202656 ESTs 4.65
438898 AI819863 Hs.106243 ESTs 4.65
428386 R17298 Hs.295923 seven In absentia (Drosophila) homolog 1 4.65
449644 AW960707 Hs.148324 ESTs 4.64
424511 BE300512 Hs.193557 ESTs, Moderately similar to ALU7.HUMAN A 4.64
415632 U67085 Hs.78524 TcD37 homolog 4.63
427779 AA906997 Hs.180780 TERA protein 4.63
422486 BE514492 Hs.117487 gene near HD on 4pl6.3 with homology to 4.63
406627 T64904 Hs.163780 ESTs 4.63
418529 AW005695 Hs.250897 TRK-fused gene 4.63
453785 AI368236 Hs.283732 ESTs, Moderately similar to ALU1.HUMAN A 4.62
416902 AA375634 Hs.288974 hypothetical protein FLJ12528 4.61
436505 AJ277841 Hs.120963 ELG protein 4.60
438378 AW970529 Hs.86434 hypothetical protein FLJ21816 4.60
442760 BE075297 Hs.6614 ESTs, Weakly slmilarto A43932 mucin 2 p 4.60
432339 AW411259 ESTs 4.60
452567 D87120 Hs.29882 predicted osteoblast protein 4.59
447850 AB018298 Hs.19822 SEC24 (S. cerevlslae) related gene famll 4.59
443171 BE28112B Hs.9030 TONDU 4.59
448854 AW245617 Hs.77703 hypothetical protein FLJ11506 4.59
423681 AB023215 Hs.131525 Homo sapiens mRNA; cDNA DKFZp434E199 (fr 4.58
420750 AW190215 Hs.62348 hypothetical protein FLJ11753 4.58 439866 AA280717 Hs.6727 Ras-GTPase activating protein SH3 domain 4.58
446719 W39500 Hs.301872 hypothetical protein MGC4840 4.58
429588 AI080271 ESTs 4.58
417171 BE613486 Hs.81412 llpin 1 4.57
452279 AA286844 hypothetical protein FLJ13164 4.57
408483 AA464836 Hs.291079 ESTs, Weakly similar to T27173 hypothet 4.57
430569 AF241254 Hs.178098 anglotensln I converting enzyme (peptdy 4.57
440773 AA352702 Hs.37747 Homo sapiens, Similar to RIKEN cDNA 2700 4.56
418422 AW440068 Hs.59425 hypothetical protein FLJ23323 4.56
447519 U46258 Hs.339665 ESTs 4.56
434834 AF156774 Hs.324020 1-acylglyceroI-3-phosphate O-acyItransfe 4.56
412560 R24601 CCR4-NOT transcription complex, subunlt 4.55
449571 AW016812 Hs.200266 ESTs 4.55
432502 NM 014641 Hs.277585 KIAA0170 gene product 4.55
422630 AA313606 Hs.13809 hypothetical protein FLJ10648 4.55
423673 BE003054 Hs.1695 matrix metalloprotelnase 12 (macrophage 4.55
443228 W24781 Hs.293798 KIAA1710 protein 4.55
427283 AL119796 Hs.174185 ectonucleotdepyrophosphatase/phosphodi 4.55
408761 AA057264 Hs.238936 ESTs, Weakly similar to (detiπe not ava 4.54
408743 AL110246 Hs.47367 KIAA1785 protein 4.54
448822 BE149845 Hs.289038 hypothetical protein MGC4126 4.54
443450 N66045 Hs.133529 ESTs 4.54
441021 AW578716 Hs.7644 H1 hlstone family, member 2 4.53
446111 W56338 Hs.13880 CGI-143 protein 4.53
436679 AI127483 Hs.120451 ESTs, Weakly slmilarto unnamed protein 4.53
433586 T85301 gb:yd78d06.s1 Soares fetal liver spleen 4.53
412811 H06382 ESTs 4.52
450770 AA019924 Hs.28803 ESTs 4.52
420439 AW270041 eukaryotc translation initiation factor 4.52
418663 AK001100 Hs.41690 desmocollin 3 4.52
430299 W28673 Hs.106747 serine carboxypeptldase 1 precursor prot 4.52
422040 AA172106 Hs.110950 Rag C protein 4.52
429504 X99133 Hs.204238 llpocalln 2 (oncogene 24p3) (NGAL) 4.51
450187 AA736788 Hs.78521 KIAA1717 protein 4.51
443257 AI334040 Hs.11614 HSPC065 protein 4.51
415691 AW963979 Hs.24723 ESTs 4.51
445867 AF272663 Hs.13405 gβphyrin 4.51
424075 AI807320 Hs.227630 RE1-sIleπclng transcription factor 4.51
445165 AV652831 Hs.234058 gb:AV652831 GLC Homo sapiens cDNA clone 4.51
421743 T35958 Hs.107614 DKFZP564I1171 protein 4.51
447805 AW627932 Hs.302421 gemln4 4.50
440146 AW014231 Hs.90790 Homo sapiens cDNA: FLJ22930 fis, clone K 4.50
448610 NM 006157 Hs.21602 nel (chlcken)-llke 1 4.50
432706 NM 013230 Hs.286124 CD24 antigen (small cell lung carcinoma 4.50
408882 H12084 Hs.31110 ESTs, Weakly simllarto MAGE-B4 [H.saple 4.49
450747 AI064821 Hs.318535 ESTs, Highly similar to 1818357A EWS gen 4.49
430178 AW449612 Hs.152475 3'UTR of: achaete-scute complex (Drosoph 4.49
419594 AA013051 Hs.91417 topoisomerase (DNA) II binding protein 4.49
435641 AI147545 Hs.114172 ESTs 4.49
420005 AW271106 Hs.133294 ESTs 4.48
402496 Target Exon 4.48
425997 AK000086 Hs.165948 hypothetical protein FLJ20079 4.48
420662 R71292 Hs.99821 hypothetical protein FLJ14547 4.48
429651 D79248 Hs.279870 ESTs, Weakly simllarto A46010 X-linked 4.48
431130 NM 006103 Hs.2719 HE4; epididymls-speclflc, whey-acidic pr 4.48
425177 AF127577 Hs.155017 nuclear receptor interacting protein 1 4.47
433323 AA805132 Hs.159142 ESTs 4.47
421437 AW821252 Hs.104336 hypothetical protein 4.47
427969 NM 001963 Hs.2230 epidermal growth factor (beta-urogastron 4.47
420798 W93774 Hs.99936 keratin 10 (epidermolytlc hyperkeratosls 4.47
440590 AI863446 Hs.266308 mosaic serine protease 4.46
452598 A1831594 ESTs, Weakly similar to ALU7 HUMAN ALU S 4.46
456439 AA251242 Hs.103238 ESTs 4.46
447574 AF162666 Hs.18895 tousled-like kinase 1 4.46
437469 AW753112 Hs.15514 hypothetical protein MGC3260 4.46
410444 W73484 Hs.132554 gb:zd54e04.s1 Soares_fetaLheart_NbHH19W 4.46
452689 F33868 Hs.284176 transferrin 4.45
447832 AI433357 ESTs 4.45
441381 H22195 Hs.31874 ESTs 4.45
425548 AA890023 Hs.1906 protect n receptor 4.45
429702 AA456883 Hs.79889 ESTs 4.45
450669 AL138077 Hs.16157 hypothetical protein FLJ12707 4.45
446742 AA232119 Hs.16085 putative G-protein coupled receptor 4.45
421814 L12350 Hs.108623 thrombospondln 2 4.45
445160 AI299144 Hs.101937 sine oculls homeobox (Drosophila) homolo 4.44
437763 AA469369 Hs.5831 tissue inhibitor of metalloprotelnase 1 4.44
449343 AI151418 protein phosphatase 3 (formerly 2B), cat 4.44
426765 AA743603 Hs.172108 nucleoporiπ 88kD 4.44
408527 AL135018 Hs.33074 Homo sapiens, clone IMAGE:3606519, mRNA, 4.44
438360 H74149 Hs.288193 hypothetical protein MGC12217 4.43
432840 AK001403 Hs.279521 hypothetical protein FLJ20530 4.43
415443 T07353 Hs.7948 ESTs 4.43
429084 AJ001443 Hs.195614 splicing factor 3b, subunlt 3, 130kD 4.43
406687 M31126 matrix metalloprotelnase 11 (stromelyεln 4.43
454417 AI244459 Hs.110826 Iriπucleotde repeat containing 9 4.43
417534 NM 004998 Hs.82251 myosln IE 4.43 421754 N76984 Hs.107922 hypothetical protein 4.42
410054 AL120050 Hs.58220 Homo sapiens cDNA: FLJ23005 fis, clone L 4.41
450684 AA872605 Hs.25333 Interleukin 1 receptor, type II 4.41
446567 NM 007247 Hs.15384 AP1 gamma subunlt binding protein 1 4.41
428474 AB023182 Hs.184523 KIAA0965 protein 4.41
446356 AI816736 Hs.14896 DHHC1 protein 4.40
447155 AA100605 Hs.121557 ESTs, Weakly simllarto DP1 HUMAN POLYPO 4.40
416852 AF283776 Hs.80285 Homo sapiens mRNA; cDNA DKFZp586C1723 (f 4.40
419713 AW96B058 Hs.92381 nudix (nucleoside diphosphate linked mol 4.40
421609 H39924 Hs.106148 Homo sapiens mRNA; cDNA DKFZp434G0972 (f 4.40
432350 NM 005865 Hs.274407 protease, serine, 16 (thymus) 4,40
451273 NM 014811 Hs.26163 KIAA0649 gene product 4.40
418757 AI864193 Hs.169728 hypothetical protein FLJ13150 4.40
415660 AI909007 Hs.78563 ubiquitiπ-conjugatlng enzyme E2G 1 (homo 4.40
439588 AA838166 Hs.174644 hypothetical protein FLJ21669 4.39
427678 BE267756 Hs.180312 mitochondrial ribosomal protein S16 4.39
418259 AA215404 ESTs 4.39
450649 NM 001429 Hs.25272 E1A binding protein p300 4.38
446783 AW138343 Hs.141867 ESTs 4.38
401464 hlstone deacetylase 5 4.38
402855 NM_001839*:Homo sapiens calponln 3, acid 4.38
448256 BE614149 Hs.20814 CGI-27 protein 4.38
442053 R35343 Hs.24968 Human DNA sequence from clone RP1-233G16 4.38
435248 AA676865 Hs.188965 ESTs 4.38
418867 D31771 Hs.89404 msh (Drosophila) homeo box homolog 2 4.38
440603 AL121733 Hs.7299 Novel human gene mapping to chomosome 1 4.38
423445 NM 014324 Hs.128749 alpha-methylacyl-CoA racemase 4.37
443242 BE243910 Hs.9082 nucleoporin p54 4.37
448360 AL117560 Hs.306352 Homo sapiens mRNA; cDNA DKFZp566P2324 (f 4.37
431562 AI884334 Hs.11637 ESTs 4.37
418565 AK001529 Hs.86149 phospholnositol 3-phosphate-bindlng prot 4.37
416801 X98834 Hs.79971 sal (Drosophlla)-like 2 4.36
434804 AA649530 gb:ns44f05.s1 NCI.CGAP.Alv1 Homo sapiens 4.36
412123 BE251328 Hs.73291 hypothetical protein FLJ10881 4.36
406081 Target Exon 4.36
413599 AJ006239 Hs.75438 qulnold dihydropterldiπe reductase 4.35
427712 AI368024 Hs.283696 ESTs 4.35
423309 BE006775 Hs.126782 sushi-repeat protein 4.35
452921 AI694200 API5-like 1 4.35
408908 BE296227 Hs.250822 seriπe/threoπiπe kinase 15 4.35
432148 AW504912 Hs.81907 ESTs 4.35
434807 AA364183 Hs.323443 hypothetical protein FLJ 11806 4.35
408056 AA312329 Hs.42331 ephrin-A4 4.35
409132 AJ224538 Hs.50732 protein kinase, AMP-activated, beta 2 no 4.35
408212 AA297567 Hs.43728 hypothetical protein 4.34
423176 AA322771 Hs.184864 Homo sapiens, clone IMAGE:3162799, mRNA, 4.34
418372 AA311833 Hs.84318 replication protein A1 (70kD) 4.34
424668 D83702 Hs.151573 cryptochrorne 1 (photolyase-llke) 4.34
437228 AL122099 Hs.75066 translin 4.34
428878 AA436884 Hs.48926 ESTs 4.33
400370 AF147075 Hs.278686 p53-respoπslve gene 3 4.33
439955 AW203959 Hs.149532 ESTs 4.33
430200 BE613337 Hs.234896 gemlnin 4.32
411450 H49619 Hs.127301 ESTs 4.32
426997 BE620738 Hs.173125 peptldylprolyl Isomerase F (cyclophllln 4.32
430791 AA486293 Hs.272068 ESTs, Weakly simllarto ALU3.HUMAN ALU S 4.31
438746 AI885815 Hs.184727 Human melanoma-associated antigen p97 (m 4.31
443941 AW016271 Hs.134883 ESTs 4.31
453323 AF034102 Hs.32951 solute earner family 29 (nucleoside tra 4.31
439108 AW163034 Hs.6467 synaptogyrin 3 4.31
431214 AA294921 Hs.348024 v-ral simian leukemia viral oncogene horn 4.30
431912 AI660552 ESTs, Weakly similar to A56154 Abl subst 4.30
425580 L11144 Hs.1907 galanln 4.30
408161 AW952912 Hs.300383 hypothetical protein MGC3032 4.30
409264 NM 014937 Hs.52463 KIAA0966 protein 4.30
421288 AI916563 Hs.178499 Homo sapiens cDNA: FLJ23117 fis, clone L 4.30
430526 AF181862 Hs.242407 G protein-coupled receptor, family C, gr 4.29
440426 AI159800 Hs.7181 Homo sapiens cDNA FLJ 13663 tis, clone PL 4.29
430691 C14187 Hs.157208 arlstaless-related homeobox protein ARX 4.29
455505 AW970640 Hs.309071 ESTs 4.29
413882 AA132973 Hs.184492 ESTs 4.29
405387 NM_022170*:Homo sapiens Wllllams-Beuren 4.29
424005 AB033041 Hs.137507 vang (van gogh, Drosophlla)-like 2 4.29
420090 AA220238 Hs.94986 ribonuclease P (38kD) 4.28
417386 AL037228 Hs.82043 D123 gene product 4.28
437866 AA156781 metallothloneln 1E (functional) 4.28
401558 ENSP00000220478*:SECRETOGRANIN III. 4.28
430315 NM 004293 Hs.239147 guanine deamlnase 4.28
432169 Y00971 Hs.2910 phosphoribosyl pyrophoεphate synthetase 4.28
436869 NM 014867 Hs.5333 KIAA0711 gene product 4.28
410561 BE540255 Hs.6994 Homo sapiens cDNA: FLJ22044 tis, clone H 4.28
429162 AK001250 Hs.197642 hypothetical protein FLJ10388 4.27
411968 AI207410 Hs.69280 Homo sapiens, clone IMAGE:3636299, mRNA, 4.27
422809 AK001379 Hs.121028 hypothetcal protein FLJ10549 4.27
442619 AA447492 Hs.20183 ESTs, Weakly slmilarto AF1647931 prole 4.27
425242 D 13635 Hs.155287 KIAA0010 gene product 4.27 413413 D82520 zinc fiπgerprotein 36 (KOX 18) 4.27
416933 BE561850 Hs.80506 small nuclear riboπucleoprotelπ polypept 4.27
420851 AA281062 Hs.29493 hypothetical protein FLJ20142 4.27
421508 NM 004833 Hs.105115 absent in melanoma 2 4.27
446100 AW967109 Hs.13804 hypothetical protein d J462023.2 4.27
431578 AB037759 Hs.261587 GCN2elF2alpha kinase 4.26
458187 D56919 Hs.265848 myo egalln 4.26
425159 NM 004341 Hs.154868 carbamoyl-phosphate synthetase 2, aspart 4.26
439186 AI697274 Hs.105435 GDP-manπoεe 4,6-dehydratase 4.25
408471 NM 012317 Hs.45231 leuclne zipper, down-regulated In cancer 4.25
451320 AW118072 diacylglycerol kinase, zeta (104kD) 4.25
420805 L10333 Hs.99947 retculon 1 4.25
424992 AW290893 Hs.96918 Homo sapiens cDNA: FLJ21561 fis, clone C 4.25
443195 BE148235 Hs.193063 Homo sapiens cDNA FLJ14201 fis, clone NT 4.25
458820 BE552151 Hs.108118 hypothetical protein FLJ22474 4.25
453455 AA063553 Hs.221931 ESTs, Weakly slmilarto JC1087 RNAhelic 4.24
448105 AW591433 Hs.298241 Transmembrane protease, serine 3 4.24
419591 AF090900 Hs.91393 Homo sapiens cDNA: FLJ21887 fis, clone H 4.24
410434 AF051152 Hs.63668 toll-like receptor 2 4.24
438186 AA779910 Hs.122128 ESTs, Weakly slmilarto VMD2.HUMAN BESTR 4.23
452833 BE559681 Hs.30736 KIAA0124 protein 4.23
450401 AW959281 Hs.8184 ESTs 4.23
408075 AA382881 Hs.42409 CGI-146 protein 4.23
445139 AB037848 Hs.12365 syπaptotagmlπ XIII 4.23
437158 AW090198 KIAA1150 protein 4.23
431736 AI912234 Hs.3297 ribosomal protein S27a 4.22
434203 BE262677 Hs.283558 hypothetical protein PR01855 4.22
418182 AW016405 Hs.16648 ESTs 4.22
428770 AK001667 Hs.193128 hypothetical protein FLJ10805 4.22
427853 AI569798 Hs.98260 ESTs 4.22
444151 AW972917 Hs.128749 alpha-methylacyl-CoA racemase 4.22
424629 M90656 Hs.151393 glutamate-cystelne llgase, catalytc sub 4.22
445929 AI089660 Hs.323401 dpy-30-like protein 4.21
452357 AI638176 Hs.283865 ESTs 4.21
418216 AA662240 Hs.283099 AF15q14 protein 4.21
440726 AL050333 Hs.306425 DKFZP564B116 protein 4.21
408548 AA055449 Hs.63187 ESTs, Weakly similar to ALUC.HUMAN llll 4.20
418126 T91451 Hs.86538 ESTs 4.20
434045 AI065133 Hs.152316 hypothetical protein PRO0971 4.20
415752 BE314524 Hs.78776 putative transmembrane protein 4.20
419480 BE536584 Hs.122546 hypothetical protein FLJ23017 4.20
432626 AA471098 Hs.278544 acetyl-Coenzyme A acetyltransferase 2 (a 4.20
416984 H38765 Hs.80706 dlaphorase (NADH/NADPH) (cytochrome b-5 4.19
424720 M89907 Hs.152292 SWI/SNF related, matrix associated, act 4.19
429227 AI961456 Hs.21275 hypothetical protein FLJ11011 4.19
437250 BE257342 Hs.94576 hypothetical protein MGC3062 4.19
429412 NM 006235 Hs.2407 POU domain, class 2, assoclatπg factor 4.19
425867 D60385 Hs.12079 calsyπtenln-2 4.19
438833 BE612940 Hs.88252 ESTs 4.18
442064 AI422867 Hs.88594 ESTs 4.18
440624 AF017987 Hs.7306 secreted frizzled-related protein 1 4.18
415728 X77337 Hs.78713 solute carrierfamlly 25 (mitochondrial 4.18
430287 AW182459 Hs.125759 ESTs, Weakly simllarto LEU5.HUMAN LEUKE 4.18
439819 BE246331 Hs.98401 Homo sapiens mRNA full length insert cDN 4.18
409151 AA306105 Hs.50785 SEC22, vesicle trafficking protein (S. c 4.18
400810 NM_006560:Homo sapiens CUG triplet repea 4.18
447898 AW969638 Hs.112318 6.2 kd protein 4.18
448412 AI219083 Hs.42532 ESTs, Moderately similar to ALU8.HUMAN A 4.18
411761 AI733848 Hs.71935 putative zinc finger protein from EUROIM 4.18
418506 AA084248 Hs.85339 Unknown protein for MGC:29643 (formerly 4.17
438054 AA776626 Hs.169309 ESTs 4.17
407756 AA116021 Hs.38260 ublqultin specific protease 18 4.16
442073 AW973443 Hs.8086 RNA (guanIπe-7-j methyltransferase 4.16
426227 U67058 Hs.154299 Human protelnase activated receptor-2 mR 4.16
435513 AW404075 Hs.42785 DC11 protein 4.16
458513 AI138322 Hs.154894 ESTs 4.16
419373 NM 003244 Hs.90077 TG-interacting factor (TALE family homeo 4.16
452862 AW378065 Hs.8687 ADAMTS2 (a dislntegrln-llke and metallo 4.15
428465 AW970976 Hs.293653 ESTs 4.15
417266 AW978515 Hs.131915 KIAA0863 protein 4.15
415786 AW419196 Hs.257924 hypothetical protein FLJ13782 4.15
432878 BE386490 Hs.279663 Plrin 4.15
412122 AW852707 G-rlch RNA sequence binding factor 1 4.15
425116 AU076686 Hs.154668 KIAA0391 gene product 4.13
433023 AW864793 thrombospondin 1 4.13
421808 AK000157 Hs.108502 hypothetical protein FLJ20150 4.13
432229 AW290976 Hs.143587 ESTs 4.13
411145 BE439553 Hs.12329 Homo sapiens, clone 1MAGE:4098694, mRNA, 4.13
442607 AA507576 Hs.288361 Homo sapiens cDNA: FLJ22696 fis, clone H 4.12
453751 R36762 Hs.101282 Homo sapiens cDNA: FLJ21238 fis, clone C 4.12
437108 AA434054 Hs.80624 hypothetical protein MGC2560 4.12
426784 U03749 Hs.172216 chromogranin A (parathyroid secretory pr 4.11
447541 AK000288 Hs.18800 hypothetical protein FLJ20281 4.11
433077 AA314262 Hs.289008 YDD19 protein 4.11
416640 BE262478 Hs.79404 neuron-specific protein 4.11
407634 AW016569 Hs.136414 UDP-GlcNAc:betaGal beta-1 ,3-N-acetyIgluc 4.11 441128 AA570256 ESTs, Weakly similar to T23273 hypothet 4.10
408031 AA081395 Hs.42173 Homo sapiens cDNA FLJ10366 fis, clone NT 4.10
407839 AA045144 Hs.161566 ESTs 4.10
425001 U55184 Hs.154145 hypothetical protein FLJ11585 4.10
449188 AW072939 Hs.347187 myotubularin related protein 1 4.10
434941 AW073202 Hs.334825 Homo sapiens cDNA FLJ14752 fis, clone NT 4.09
409439 AW390511 Hs.288862 Homo sapiens cDNA: FLJ21260 (Is, clone C 4.09
424243 AI949359 Hs.143600 ESTs, Highly similar to cis Golgi-locali 4.09
439606 W79123 Hs.58561 G protein-coupled receptor 87 4.08
407999 AI126271 Hs.49433 ESTs, Weakly similar to YZ28.HUMAN HYPOT 4.08
414962 AF273304 Hs.235376 XPMC2 protein 4.08
452512 AW363486 Hs.337635 ESTs 4.08
429024 AI652297 Hs.119302 complement-clq tumor necrosis factor-rel 4.07
434288 AW189075 Hs.116265 fibriliω 4.07
438472 AW974907 Hs.86228 TRIAD3 protein 4.07
449543 AF070632 Hs.23729 Homo sapiens clone 24405 mRNA sequence 4.07
439541 AW970853 Hs.336214 ESTs 4.06
435803 Z44194 Hs.4994 transducer of ERBB2, 2 4.06
429250 H56585 Hs.198308 tryptophan rich basic protein 4.06
437994 U92012 Hs.251659 ESTs, Weakly slmilarto mariner transpos 4.06
434725 AK000796 Hs.4104 hypothetical protein 4.06
440006 AK000517 Hs.6844 NALP2 protein; PYRIN-Contalnlng APAF1-II 4.05
424259 AK001776 Hs.143954 hypothetical protein FLJ10914 4.05
426572 AB037783 Hs.170623 hypothetical protein FLJ11183 4.05
434517 AA635690 Hs.337251 hypothetical protein MGC2487 4.05
425397 J04088 Hs.156346 topolsomerase (DNA) II alpha (170kD) 4.05
434033 AI631749 Hs.156616 ESTs, Weakly similar to alternatively sp 4.05
431341 AA307211 Hs.251531 proteasome (prosome, macropain) subunlt, 4.05
427699 AW965076 Hs.180378 hypothetical protein 669 4.04
422765 AW409701 Hs.1578 baculoviral IAP repeat-containing 5 (sur 4.04
452408 AA306477 Hs.29379 hypothetical protein FLJ10687 4.04
412708 R26830 Hs.106137 ESTs, Weakly similar to CGHU7L collagen 4.04
424232 AB015982 Hs.143460 protein kinase C, nu 4.04
432945 AL043683 Hs.8173 hypothetical protein FLJ10803 4.04
430132 AA204686 Hs.234149 hypothetical protein FLJ20647 4.04
431585 BE242803 Hs.262823 hypothetical protein FLJ10326 4.04
410660 AI061118 Hs.65328 Fanconl anemia, complementation group F 4.04
414013 AA766605 Hs.47099 hypothetical protein FLJ21212 4.04
414696 AF002020 Hs.76918 Niemann-Plck disease, type C1 4.04
419638 N46504 Hs.91747 profilln 2 4.04
446487 AA195526 Hs.44625 Rad50-lnteractng protein 1 4.03
419749 X73608 Hs.93029 sparc/osteonectln, cwcv and kazal-like d 4.03
444864 AW965446 Hs.81907 ESTs, Weakly simllarto T26501 hypothet 4.03
445921 AW015211 Hs.146181 ESTs 4.03
422005 BE266556 Hs.110702 Homo sapiens mRNA; cDNA DKFZp761E212 (fr 4.03
406922 S70284 Hs.119597 gb:stearoyl-CoA desaturase [human, adlpo 4.03
433149 BE257672 Hs.42949 hypothetical protein HES6 4.02
421182 AA284855 Hs.104480 ESTs 4.02
417691 AU076610 Hs.82399 low density lipoproteln receptor defect 4.02
451253 H48299 Hs.26126 claudin 10 4.02
446950 AA305800 Hs.5672 hypothetical protein AF140225 4.01
435020 AW505076 Hs.301855 DIGeorge syndrome critical region gene 8 4.01
432278 AL137506 Hs.274256 hypothetical protein FLJ23563 4.01
452066 AA772149 Hs.16979 ESTs, Weakly similar to A43932 mucln 2 p 4.01
444700 NM 003645 Hs.11729 fatty-acld-Coenzyme A llgase, very long- 4.01
417777 AI823763 Hs.7055 ESTs, Weakly similar to I78885 serine/th 4.00
441647 AA534210 Hs.285280 Homo sapiens cDNA: FLJ22096 fis, clone H 4.00
453063 W47196 Hs.166172 aryl hydrocarbon receptor nuclear transl 4.00
432834 F06459 Hs.289113 cytochrome b5 reductase 1 (B5R.1) 4.00
419457 AA243146 Hs.209334 ESTs, Moderately similar to S23A.HUMAN P 4.00
452253 AA928891 Hs.28608 Homo sapiens cDNA: FLJ22115 fis, clone H 4.00
TABI F 6B
Pkey: Unique Eos probeset identifier number
CAT number. Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accession
449230 6182.6 BC006329 AK026224 BG105365 AI472084 AW074277 AI743908 BM309990 BI850432 AI094365 AI539568 AW779999 AI261365 AA988975 AI436272 AI559886 BI710742 AA988508 AA036678 AI867147 AW518513 AI620019 BE645777 AI801919 AW205320 AI457722 BF061996 BF061798 AA233854 AA232795 AA516294 AA830561 R74220 BG768337 AW392972 BE764979 BE257665
429228 215430.1 BG676155 BM009591 AI479075 AI025794 AI017967 AA448270 BE466812 AA853422 AI392649 BG952034 AA513384 BF840124 BE714620 AW969605 AI553633
447329 9170.1 BC001573 AK074197 AW967044 AW360965 AW612048 AI765501 AA112034 BI859391 BI334670 W63553 AV706135 AW024203 BI194441 AV655141 AA316041 BE280583 BG428780 BE267060 AV648926 AA317168 BI222294 BG437688 BE709273 AI951240 AI611162 AW970792 H89338 BE543309 AL036038 R26941 BI765176 AA209487 AA111975 AA086463 AW192209 AW025245 BF511894 AW264490 AW014985 AA947336 F15843 BI335083 AA563626 BE546579 AW470009 AA083693 BE090517 BF970294 BG427898 BE541527
428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 AI92B140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658 AA769094 BF446026 AW118719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704 AI356361 AI923640 AW070509 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311 AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 BI061872 BI059498 AA134476 AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166 412446 63467 1 BC021735 A1669212 AL120184 AI769949 BFΞ701002BE184363 BE819031 BG702238 BF090049 BF963318 BF961912 BF943013
AA934514 AA151245 BF960659 AA987907 Z41449 BF908059 BF908053 BF908049 BE699424 BF908060 BF962832 BF952020 BF963134 5 BI035538 BF908052 BF908057 BF090026 BF943158 AI632924 BF512340 BF952021 BF960776 BF943437 BF942847 AI768015 F09778
F04816 F02721 AA102645 AI633838 AA617929 BF947001 BI035448 BE935876 AW890837 AW898604 BF957405 BF963433 BG704815 412636 1438 1 M77830NM 004415 AF1390B5 BG681115 BG740377 BI712964 BG000656 AA128470 BI438324 H2740B BE931630 BE167165 AW370827
AW370813 J05211 BG698865 BG740734 BG680618 BG739778 BI765807 BM353403 BM353248 AW177784 AW205789 AW951576 AW848592 BE182164 BF149266 BE940187 BI060445 BI060444 BF350983 BE720095 BE720069 BE715154 BE082584 BE082576 0 BE004047 AA857316 BI039774 BE713818 BE713548 AW170253 BE160433 BI039775 AW886475 BM462504 BE931734 BF149264
AA340777 BF381183 BG621737 AU127260 AW364859 BF993352 BG223489 BE819009 BF381184 BE715956 R58704 AA852212 AW366566 BI090358 BF087707 BE819046 BE819005 AA377127 BE073467 BE819069 BE819048 BI036306 BG990973 BI040954 BF919911 AU140155 AI951766 AI434518 AW804674 BF752969 BE837009 BE925826 BF149265 AW995615 BE814264 BI039782 AU140407 BE144243 BE709863 BF985642 BE001923 BF933510 AW265328 BG436319 BE182166 AW365175 AW8476B8 BE818280 5 AW177933 BF873679 AW178000 BE082526 BF476866 BF086994 BF592276 BE082507 BE082514 BE082505 BF873693 AW068840
AW847678 BF804153 AW365157 BE813930 BE002030 AW365153 BE184941 BF749421 BE184920 BF839562 BE184933 BF842254 BE698470 BE931048 BF999889 BF368816 BE184924 BE159646 BE714632 BE184948 BG986845 AA13112B AA099891 W3948B C04715 BF096124 BE865341 AW799304 AL603116 BE149760 BE705967 BE705966 BE705968 AWB48723 AW376699 AW376817 AW376697 BG005097 BF751115BE696084AW848371 AW376782AW848789AW849074AW361413 BF927725 BF094211 AW997139 BE865474 0 BE185187 BE156621 BE715089 BE713297 BE713298 BE179915 AW799309 BF872345 BF088676 BE705939 AW752599 BG005197
BF350086 BE715196 BE715155 BF752396 BF093817 BF831190 BF752409 BE006561 BG959922 BF094833 BF094748 BF094583 AW377699 AW607238 BE082519 AW377700 BF349467 AI190590 AI554403 AI392926 AU158477 BI467252 AU159919 AI760816 BF082516 AI439101 AA451923 AI340326 AI590975 BI791553 AI700963 AI142882 AA039975 AA946936 AA644381 BM314884 AA702424 AI417612 AW190555 AI220573 AI304772 AI270345 AI627383 AA552300 AI911702 AW166807 AI346078 W95070 AA149191 AA026864 AI830049 5 AW780435 AI078449 AI819984 AI858282 BI46858B AIB60584 AI025932 AA026047 AA703232 AA658154 AA515500 AW192085 AA918281
T77861 AI927207 AI205263 BF082491 AW021347 AI568096 BE939862 AA088866 D12062 AA056527 AA782109 W19287 W02156 AW150038 AA022701 T87181 H44405 AI910434 BF082513 AI494069 AI270027 AI635878 AA128330 BG681425 BE706078 R20904 BG680059 BG676647 BF764409 AA026654 AV745530 BI762796 BG287391 AW798780 BE706045 BE926470 AW799118 BF087996 BE002273 AW879451 AI571075 BE067786 AV721320 AI022862 N29754 C03378 N84767 AA131077 H30146 BE714290 AI686869 0 AI568892 AI915596 AW105614 AI887258 AI538577 BE926474 BE067737 BG319486 AA247685 AW798883 AW103521 BF989173
AW860878 BE939707 BE185750 BE714064 BE713903 BE713868 BE713763 BG950164 BE713810 AW365151 BG955489 BE005272 BF915937 AW365148 A1905927 BF992780 AW853812 BG954443 BI770853 BG679406 BG740832 BG681087 BG698430 AA455100 T87267 BE696209 BE696210 BI089483 BE006273 BE872225 AW391912 BE925515 BG677012 BG741970 AA026480 BE705999 BG677157 BE009090 BG681378 BE712291 BG961498 BG678984 BI040941 AA337270 AW384371 AW847442 BI058659 BE813665 5 W95048 W25458 AW177786 AA025851 BE931733 BF154837 BG949393 BE714441 AW996245 BE711801 AI284090 BE064323 BE719390
BE940148 BG991212 BF375714 BF349522 BG996267 T48793 BI013292 BE001925 AW365156 AW365154 AW606653 BF763109 BE931637 BE167181 BE713879 BF354008 BF678726 H90899 AW365145 W38382 AI498487 449349 852 3 BG679689 AW856638 BM016319 BE327123 AW772128 BE693337 BE938262 BG013928 BF892774 BF894765 BF892588 BF890995
BE155056 BE153569 AI934407 BE672538 AW204203 AA778306 BE502974 AI718504 AA778312 AW008224 AW299732 AI911561 0 AI867457 AI521962 AI640173 AI823832 AI288888 BE467960 AI934441 AA483527 AW612103 AI802712 AW342106 AI580299 AW083293
AI700874 AW469932 AI583726 AW302136 BE327360 AW614404 C02300 AA934834 F29737 AI262050 AA934619 AA535965 BF196507 AA393480 BF086615 AI825386 AA009773 BI333272 T93614 AW770207 BF766665 T64641 W92713 R94110 T89897 BF086603 T93659 AA001207 BE539257 BE541430 BE160783 BE155304 BE155454 BF891405 BF762818 451807 17758.2 BM479185AL552795AL577722 BF0388B8 BM127617 BF510346AW450652AA865478 AW449519 BM127314 AI806539 AW449522 5 AA993634AI827626AA904788
446873 15731 1 BC016767 Z30093 NM 001516 BI753904 AL555563 AL598882 BG706296 BG723901 AL600911 AW949486 AL602675 AL600169
AL60011. AI373329 BF149149 AU099109 AL578036 AA410532 AA521208 BI018894 BI333338 AW269273 N79350 AW954400 A1760772 AA765916 AW300373 AW628851 AW505118 AA506136 AW779373 AI675026 BE674159 AI241579 N51870 AI632936 AI796901 AI620962 AA876979 AA886127 AA934448 H58689 AA373345 N78420 AA282406 N98953 N22575 N62381 AA805377 AV718946 AI421009 D20327 0 AW518433 AI554439 BI027833 BG613441 BG573433 N66669 N62701
450377 12109.1 AB033091 AL520743 BE811813 N53332 N99716 AL561910 AA280655 BE710392 AV705100 AW293978 AW444556 AA281459 AI679751
AI873695 BG700891 BI553517 R80518 BG779771 BG534451 AA479402 AW961580 BF061430 AI857643 AI768486 AW512118 AA479302 A 770384 AW072470 AI041596 AI049699 A 592865 AA976261 BE879747 BG114119 AW183811 AA909938 BF571621 BF350794 BF351375 BE925699 AL050294 BC010371 BF982270 AL042656 BF095732 AW812618 BF095731 BG212397 BF678765 BI038602
55 BG388664 AW675337 BG289398 BE939598 AW805570 AA527097 AW150540 AI693720 AA743364 AI915793 N48185 AI573107 AA043474
AI351615 AI969490 AI910763 R50866 AI699181 N73808 H08164 451752 10408 5 AB032997 AI141678 AW978722 BE467119 A1761408 BF727385 AW237035 AI934521 BF436248 AI479668 Z40632 AA832081 AW295901
BF057835 BE465977 AI621269 BE465983 BF756369 N74056 AI817896 AA716567 AA934774 H62600 H09497 BF943762 BE395335 BE883333
60 400247 2764 1 BC022339BC009610 BC010537X79805 NM.006713U12979 BM467814 BM450743AU132951 AU137129 BG493425AV758819
BG708412 BG705885 BG702217 AV716638 BG777009 BI545689 BI552153 BM476712 BG770858 BG527656 BG528277 BG391388 AV716861 BI602926 BG290073 BI667399 BM451469 BI667173 BI602139 BG532171 BI669216 BI544727 BG721852 AV716503 AV701327 BM09073B BI492000 AI308856 BI544904 AL599813 AV715829 AV716505 AV714587 AV717902 BF668072 AV7163B5 BI461927 BM090954 _ _ AV717826 BG503676 AV647719 BG501392 BG428433 BE895629 BM313117 AW021050 BG435032 BM152910 AA313503 AA872377
65 BG574714 AV712054 AV732696 AA252476 AV712759 AL599643 BE790872 BG654930 W73337 AW675377 AV760376 AV725139
AV716379 AA887165 BE830003 AW023796 AL599291 AI902948 BG944042 F00781 AA352483 BG217897 N33888 AW581924 BG654730 D31410 AA353088 D31288 AA295029 H95170 BE935104 AU139980 BG772963 BG776470 BG532512 BG105449 BI545421 AV715456 AW386083 BG699714 AL535832 AL514940 BG190861 BG210593 AW999254 H95138 AA353863 BE764809 N50375 BE091363 BG701255 BI860846 BI832485 BG168150 BG028647 BE546301 BG900321 BI909737 BG702363 BG614141 BG611137 BG700121 BF031492 N85802
70 AV715940 N51590 BG993478 BE172016 AW893622
444172 49300 2 BF526827 AA513594 AL515291 AV648373 AV648176 AA916789 BF002906 A 469960 BE466943 AI367749 AI5597.5 BF431260
AA937968 AI422252 AI288937 BF962778 AA909144 BF960004 BE671534 AI271719 BF925335 BE669504 BF433431 BF924838 AI218062 AW960577 AV722716 BI859067 BF944964 BE147740 BF938993
_ 414883 8371.2 AF274943 BG494894 AI719075 AA908783 AI935150 AI422691 AA910644 AA583187 BM272167 AI828996 AA527373 AW972459 AIB31360
75 AA772418 AI033892 AA100926 AU154749 AI459432 AI423513 AI094597 AA740817 AI991988 AI090262 AI312104 BI256707 AA459522
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AW438593 AA702328 AA262137 AI379307 AA281632 AA694381 AI422791 AW243902 AA493261 AI868989 D62032 BG529976 BE504426
AA369546 AW869612 AW021723 AW965366 AW117912 AI742020 AW970160 AA514538 AW449526 AW082476 N99706 AA262413
AA333518 BG822620 AA643040 AW236597 BE220653 AA768827 AI081788 AA877024 N71978 AA612940 AI290151 AW082653 AI383270
C16425 AA722211 AI539327 AA369545 AA522467 N93082 AI371310 AW082649 AW270041 AI292303 BF856785 D19612 AI701667
R50985AW869643
452598 2741J AK055715 AI129800 AW027959 AI927949 AI650270 AW514661 AI708393 AL138076 AI926721 AA749139 AI399955 AW874011 AI302816
AI242763 AA828301 AA262795 AI093249 AI084565 AA904444 BE245661 AI810709 N30447 AI653617 AI289975 AI474418 AA737455
AI619613 AA291708 AI640264 N91446 AW029069 AA680378 AA338773 BC022321 BM450359 BE439944 AA521348 AI066761 AL138075
BM153113 BM153112 AW182953 BM147809 A1247395 A1911116 AA977587 AA291690 AI243777 F35824 AA579199 B 479711 AW961031
H92980 H86861 AA026904 AI052445 R92739 T10789 AV749986 AL540531 AA452953 BM152599 AA382769 BI550695 BG432646
AV744808
447832 1036795.1 AI628543 AI433357 A 772732
449343 14470.1 AK055378 BE896063 AV722833 BI032095 BF952019 BG547204 AI151418 W03542 W60401 AI346936 AA862855 W60310 N72501
BF963436 C04881 H90060 AA001203 AI863984 AI932612 AI499771 AI187944 AA501896 AA714924 H00689 AA918680 AA573998
AA521308 AW182868 BF996707 AA908959 AI628880 AW173363 AW665845 AA130178 AI818267 AI653663 AI828924 AA746655 AI951984
AI635625 AI093113 AI377976 AI624029 AI418242 R76291 W92652 AI207798 AV706224 AA742467 AA641806 W61229 AA130170
AA160170 H85007 W72474 W61163 H97873 AL047509 R76567 AA812071 H81599 AA021275 H85004 H85894 BG537537 BF830518
W76228 W46673 Z43839 R78710 C01747 H00789 BI036345 W92828 BE150445 AW380821 AW173095 H85630 H81598 H86032 R84855
R13223 AA774992 406687 0.0 M31126
418259 133853.1 B 310925 AA426110 B 310629 BF434286 A 015091 8F475996 AW118867 BE675186 AI688568 AI453594 AW590S89 AI652425
AI827969 BF056946 AI802866 AI393380 AI476224 AW590639 AW136271 AI458252 AI524726 AA843768 AA782158 AI336058 AI097532
AW451563 AA459408 AA459633 AA418444 W23607 BG940150 AI493445 AW054729 AI221929 AI868744 AA215405 AA766713 AA621546
BF928317 BE464132 AI990909 AW271459 AI262061 AA215404 N74332 BG940151 BG952261 AA972115 W96315 AA689586 R69057
BF766886 BE769254 W05240
434804 118455 1 AA659316H64973AA649530
452921 92089J AW977983 AA029637 AA029697 AA806003 BF808645 W74124 AA809498 T17497 BE549804 W79644 BF446767 AI694200 AA988927
BE047252
431912 610.10 BI763666 BI517886 BI759051 AI688604 AI660552 BF588523 AW004785 AW295479 BF591117 BF002672 BF064073 AA594441 AI380340
AI700219 AI659950 AI688540 AW296326
437866 34267.1 U52054 AL581000 AA156850 AW293839 BI335865 AA024963 BF149420 BE073977 AW602574 BE164012 BE163992 BE163974
AW402161 BM194134 AW966609 W84374 BF916380 AA385173 W84366 AA383743 BF903598 AA043776 W84421 AA778446 AW444904
BF446960 AA837481 AV755539 AW468444 AW468002 AA811830 AA581806 AI866686 AI572124 AA687333 D20160 AA812489 AU185248
AU186004 AA156781 AI536733 BM144850 AI4718B3 AA040926 BF507639 AA043777 AW874142 BE832523 BE163972 BI022546 BI021204 413413 26025 3 BG261240 BG231707 AI440201 BF540868 BF240794 BE779394 BG505096 AA129208 D82298 T10758 AU155599 BF857123 BF836348
451320 12225.2 AK057B26 A1631982 AA224195 AI701458 AA890570 AW966562 AW071907 AI671352 AI375892 T03517 AI124088 R88265 AI084316
BF223720 AI354686 T33652 AW205836 BE931115 AI720211 T03490 BF084055 AI372637 T15415 BG054890 AA630384 F26326 AI140719
AA443303 T33230 T33623 T33511 T33785 AW118072 W20198 AI657180 T15734 AI419606 N90552 AA224388 T15909 T03515 D55612
W27899 437158 59575 1 AL050068 AA160485 AW173544 AW296506 AW439860 AI521563 AI702529 AI393606 AW138323 AA570109 H19504 BM021968 BF063327
BF593552 AA630766 AI597717 AI807128 AA523012 AI356250 AW451857 AA974203 AI762577 BF512552 AW007307 BE675286
AW450602 AA962057 AW516069 AI582546 BF221924 BF222543 AI801808 AW468599 AW000736 AI866625 AW235356 BM021837
AA911956 AI680606 W86516 T03370 AW611634 H41653 A1468349 H19588 AW090198 AW043993 R39847
412122 3941.2 AK056423 AW070901 BG222419 BF928848 AL567752 AW770702 BE160226 AW248894 AI304851 AI090802 BF514704 AI659696
AI762084 BE018718 AI088023 BF876482 AA283824 BF742200 AI349494 AI942345 AL576641 BG959608 AA853964 AA854927 AA767839
AI955028 BG611080 BI497416 AW947186 AI703492 AW612137 AI696372 BM016022 AW852632 N57282 BI859575 AA100379 AI879394
AI653605 BM459051 AI446574 BG031916 BI004602 BM014817 AA725075 BE063022 BG741166 BF088949 AI937125 AW936878
433023 3970.8 BE999967 BF438599 AW864793 AI802899 BE815132 AW468888 AI672189 AI052004 BF112024 AA772335 AW275054 AA573845
AI144148 AI968683 AA846676 AA927355 H80424 AW973295 R88209 F29868 BE928871 441128 20932.1 BC014072 BE328850 AI356567 AI148171 AI022165 BG149661 BFO00671 AA233101 AA573721 AA447991 AW016855 AI005068 AA554071
BF478215 AA906902 AW014761 BE905651 BE512923 BM047129 AA243852 AA232991 AA127550 AA127551 AA570256 AI473237
BF033706 N90525 AW973623 AI359627 BG674574 BE903322
TABLE 6C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers In this column are Genbank Identifier (GI) numbers. "Dunham I. et al." refers to the publication entted "The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402-489-495. Strand: Indicates DNA strand from which exons were predicted. NLpositlon' Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLpositlon
406399 9256288 Minus 63448-63554
403149 9799833 Plus 25034-25185
401197 9719705 Plus 176341-176452
401451 663406B Minus 119926-121272
405770 2735037 Plus 61057-62075
401519 6649315 Plus 157315-157950
404440 7528051 Plus 80430-81581
402736 9212044 Minus 66876-67010
401866 8018106 Plus 73126-73623
404568 9966995 Minus 92893-93116
401403 7710966 Plus 146180-146294
402812 6010110 Plus 25026-25091,25844-25920
402802 3287156 Minus 53242-53432
404996 6007890 Plus 37999-38145,38652-38998,39727-39872,4055
400583 9887611 Minus 201148-201272
402053 8083229 Plus 62703-63179 400880 9931121 Plus 29235-29336,36363-36580
402408 9796239 Minus 110326-110491
401747 9789672 Minus 118596-118816,119119-119244,119609-11976
403485 9966528 Plus 2888-3001,3198-3532,3655-4117
403817 8962065 Plus 110297-111052
402496 9797769 Minus 8615-9103
401464 6682291 Minus 170688-170834
402855 9662953 Minus 59763-59909
406081 9123861 Minus 38115-38691
405387 6587915 Minus 3769-3833,5708-5895
401558 7139678 Plus 103510-104090
400810 8567959 Minus 174204-174331,175062-175205
TABLE 7A: About 381 genes upregulated In lung metastases to the brain relative to normal body Bssues
Pkey: Unique Eos probeset Identifier number
ExAccn: Exemplar Accession number, Genbank accession number
UniGenelD: UniGene number
UniGene Title: UniGene gene title
R1: 90th percentile of lung metastases to the brain Als divided by the 90th percentile of normal body tssues Als, where the 15th percentle of all normal body tissue Als was subtracted from the numerator and denominator.
SEQ ID NO(s): SEQ ID number(s) for nucleic acid and protein sequences associated with table entry.
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s):
427383 NM.005411 Hs.177582 surfactant, pulmonary-associated protein 4.88 49106 431433 X65018 Hs.253495 surfactant, pulmonary-associated protein 3.75 58 112 442275 AW449467 Hs.54795 Homo sapiens secrβtoglobln, family 3A, m 5.20 66 444342 NM.014398 Hs.10887 similar to lysosome-assoclated membrane 2.78 70 118 450726 AW204600 HUMPSPBA Human pulmonary surfactant-asso 3.52 77 426251 M24283 Hs.168383 Intercellular adhesion molecule 1 (CD54) 3.24 45 103
X03068 Hs.73931 major histocompatibllity complex, class 2.62 486
431164 AA493650 Hs.94367 thyroid transcription factor 1 5.90 57 428438 NM.001955 Hs.2271 endolhelln 1 2.75 51 107 412869 AA290712 Hs.82407 CXC chemokine ligand 16 2.50 19 414517 M24461 Hs.76305 surfactant, pulmonary-associated protein 27.02 457200 U33749 Hs.197764 thyroid transcripUon factor 1 9.15 421798 N74880 N-acylsphlngoslπe amldohydrolase (acid c 6.86 412870 N22788 Hs.82407 CXC chemokine ligand 16 2.67 448133 AA723157 Hs.73769 folate receptor 1 (adult) 2.62 421502 AF111856 Hs.105039 solute carrier family 34 (sodium phospha 7.84 427834 AA506101 Hs.285813 hypothetical protein FLJ11807 2.57 400328 X87344 transporter 2, ATP-binding cassette, sub 2.82 427700 AA262294 Hs.180383 dual specificity phosphatase 6 2.50 425371 D49441 Hs.155981 mesothelin 6.28 424273 W40460 Hs.144442 phospholipase A2, group X 2.63 414945 BE076358 Hs.77667 lymphocyte antigen 6 complex, locus E 3.49 432006 AL137382 Hs.272320 Homo sapiens mRNA; cDNA DKFZp434L1226 (f 5.44 418067 AI127958 Hs.83393 cystatln E/M 2.99 428970 BE276891 Hs.194691 retnoic acid Induced 3 (RAIG1); metabo 3.24 435472 AW972330 Hs.283022 triggering receptor expressed on myeloid 6.14 425211 M18667 Hs.1867 progastricsln (pepslnogen C) 19.38 414915 NM.002462 Hs.76391 myxovlrus (influenza) resistance 1 , homo 2.82 431630 NM.002204 Hs.265829 Integrin, alpha 3 (antigen CD49C, alpha 3.27 416700 AW498958 Hs.343475 cathepsln D (lysosomal aspartyl protease 2.63 430300 U60805 Hs.238648 oπcostatin M receptor 3.07 413278 BE563085 Hs.833 Interferon-stlmulated protein, 15 kDa 4.60 413936 AF'113676 Hs.297681 serine (orcystelne) proteiπase Inhlblto 2.67 413527 BE250788 Hs.179882 hypothetical protein FLJ12443 2.85 435575 AF213457 Hs.44234 triggering receptor expressed on myeloid 3.06 419092 J05581 Hs.89603 mucln 1, transmembrane 3.25 454453 AW752781 hypothetical protein FLJ12614 slmilarto 2.86 427621 BE621182 Hs.179882 hypothetical protein FLJ12443 3.63 409917 H07989 Hs.4302 ESTs, Weakly similar to T29299 hypothet 2.50 436939 AA853680 Hs.5345 arglnyl amlπopeptdase (amlnopeptdase B 2.71 400245 Eos Control 2.68 432941 W04803 Hs.279851 hypothetcal protein FLJ10241 2.50 410731 AK001531 Hs.66048 hypothetical protein FLJ10669 2.68 429380 AF023268 Hs.200600 secretory carrier membrane protein 3 2.64 444198 AI345232 Hs.153503 hypothetical protein FLJ22529 2.64 429547 AW009166 Hs.99376 FGENESH predicted novel secreted protein 2.91 450296 AL041949 Hs.24756 hepatocyte growth factor-regulated tyros 2.59 426410 BE298446 Hs.305890 BCL2-like 1 2.51 433029 NM.014322 Hs.279926 opsln 3 (encephalopsln) 2.62 413719 BE439580 Hs.75498 small Inducible cytokine subfamily A (Cy 2.98 440340 AW895503 Hs.125276 ESTs 2.75 418057 NM 012151 Hs.83363 coagulation factor Vlll-assoclated (Intr 2.73 421110 AJ250717 Hs.1355 cathepsln E 3.11 425676 AW410656 Hs.159161 Rho GDP dissociation Inhibitor (GDI) alp 2.57 444006 BE395085 Hs.10086 type I transmembrane protein Fn14 2.92 409420 Z15008 Hs.54451 lamlnin, gamma 2 (nlceln (100kD), kallnl 3.28 440672 AF083811 Hs.7345 MAD1 (mltotlc arrest deficient, yeast, h 2.89 407242 M18728 gb:Human nonspecific crossreactlπg antlg 2.85 448641 R31845 Hs.21666 Insullπ-IIke 4 (placenta) 2.80 430044 AA464510 Hs.152812 ESTs 2.55 408748 J05500 Hs.47431 spectrin, beta, erythrocytlc (Includes s 2.59 447699 AB011116 Hs.284251 KIAA0544 protein 2.62 429978 AA249027 ribosomal protein S6 2.96 416971 R34657 Hs.80658 uncoupling protein 2 (mltochondrtal, pro 2.78 436238 AK002163 Hs.301724 hypothetical protein FLJ11301 2.79 413585 AI133452 Hs.75431 flbrlnogen, gamma polypeptide 3.01 416448 L13210 Hs.79339 lectln, galactoslde-blndlng, soluble, 3 2.86 419152 L12711 Hs.89643 traπsketolase (Wemlcke-Korsakoff syπdro 2.6B 408663 Hs.298351 alveolar soft part sarcoma chromosome re 2.68 439453 BE264974 Hs.6566 thyroid hormone receptor Interactor 13 3.98 432320 AW411066 Hs.274351 CGI-89 protein 2.66 424179 F30712 Hs.334573 Homo sapiens, clone IMAGE:4285740, mRNA 2.67 451698 Y16187 Hs.26880 endothellπ converting enzyme-like 1 3.24
400213 NM_014847*:Homo sapiens KIAA0144 gene pr 2.59
450065 AL050107 Hs.24341 transcriptional co-activator with PDZ-bl 2.60
410407 X66839 Hs.63287 carbonic anhydrase IX 2.88
452827 AI571835 Hs.55468 ESTs 2.57
437915 AI637993 Hs.202312 Homo sapiens clone N11 NTera2D1 teratoca 3.18
447349 AI375546 gb:tc23d04.x1 Soares_totaLfetus_Nb2HF8_ 2.71
447131 NM 004585 Hs.17466 retnolc acid receptor responder (tazaro 3.21
447250 AI878909 Hs.17883 protein phosphatase 1G (formerly 2C), ma 2.59
439841 AF038961 Hs.6710 mannose-P-dolIchol utilization defect 1 2.72
400203 Eos Control 2.87
429544 BE299343 Hs.2430 transcription factor-like 1 2.93
407244 M10014 fibriπogen, gamma polypeptide 4.25
445982 BE410233 Hs.13501 pescadillo (zebrafish) homolog 1, coπtal 2.71
422083 NM 001141 Hs.111256 arachldonate 15-llpoxygenase, second typ 3.55
451063 AW163702 Hs.25911 HLA-B associated transcript-2 2.87
421975 AW961017 Hs.6459 hypothetical protein FLJ 11856 2.74
407756 AA116021 Hs.38260 ubiqultln specific protease 18 3.09
410102 AW248508 Hs.279727 ESTs; homologue of PEM-3 [Clona savlgnyl 3.90
431250 BE264649 Hs.251377 taxol resistance associated gene 3 2.57
437387 AI198874 Hs.28847 AD026 protein 2.76
456950 AF111170 Hs.306165 Homo sapiens 14q32 Jagged2 gene, complet 2.54
412817 AL037159 Hs.74619 proteasome (prasome, macropaln) 26S subu 2.58
456031 AA335996 eukaryotic translation Initiation factor 2.76
406685 M18728 gb:Human nonspecific crossreacting antlg 3.21
437270 R18087 Hs.323769 cisplatn resistance related protein CRR 3.28
416976 BE243985 Hs.80680 major vault protein 2.79
449976 H06350 Hs.135056 Human DNA sequence from clone RP5-850E9 3.21
419705 AW368634 Hs.154331 ESTs 2.92
420234 AW4O4908 Hs.96038 Ric (Drosophlla)-llke, expressed In many 3.06
429619 AL120751 Hs.211568 eukaryotic translation Initiation factor 2.60
410575 BE207480 Hs.6994 Homo sapiens cDNA: FLJ22044 fis, clone H 2.84
458176 AI961519 Hs.140309 Homo sapiens, clone IMAGE:3677194, mRNA, 2.79
411773 NM 006799 Hs.72026 protease, serine, 21 (testlsln) 3.28
437852 BE001836 Hs.256897 putative GPCR 2.60
425236 AW067800 Hs.155223 stannlocalciπ 2 2.78
416018 AW138239 Hs.78977 proprotein convertase εubtilisln/kexln t 2.84
452732 BE300078 Hs.80449 Homo sapiens, clone IMAGE:3535294, mRNA, 2.73
427584 BE410293 Hs.179718 v-myb avlan myeloblastosls viral oncogen 2.65
417881 AI879117 Hs.7991 gb:au54g09.y1 Schneiderfetal brain 0000 2.60
453012 T95804 Hs.31334 putative mltochondrial outer membrane pr 2.57
443179 AI928402 Hs.6933 hypothetical protein FLJ12684 2.83
432226 AW182766 Hs.273558 phosphate cytdylyltransferase 1, cholin 2.86
458748 AI381530 gb:te76d07.x1 Soares_NFL_T_GBC_S1 Homo s 2.95
418678 NM 001327 Hs.167379 cancer/tests antigen (NY-ESO-1) 2.67
427719 AI393122 Hs.134726 ESTs 2.54
418399 AF131781 Hs.84753 hypothetical protein FLJ12442 2.94
446872 X97058 Hs.16362 pyrlmldlnergic receptor P2Y, G-protelπ c 4.04
459255 AI493244 Hs.239500 hypothetical protein MGC13114 2.79
415989 AI267700 ESTs 2.85
435151 AA348482 Hs.4788 nicastrin 2.74
421846 AA017707 Hs.1432 protein kinase C substrate 80K-H 2.58
422997 BE018212 Hs.122908 DNA replication factor 2.81
422675 BE018517 Hs.119140 eukaryotic translation Initiation factor 2.53
447733 AF157482 Hs.19400 MAD2 (mitotc arrest deficient, yeast, h 3.06
401131 NM 001651*:Homo sapiens aquaporln 5 (AQP 2.53
430454 AW469011 Hs.105635 ESTs 2.93
426318 AA375125 Hs.147112 Homo sapiens cDNA: FLJ22322 fis, clone H 2.71
421541 NM 003942 Hs.105584 ribosomal protein S6 kinase, 90kD, polyp 2.60
421506 BE302796 Hs.105097 thymldlne kinase 1, soluble 2.64
422532 ALO08726 Hs.118126 protective protein for beta-galactosldas 2.66
451481 AA300228 Hs.295866 hypothetical protein DKFZp434N1923 3.17
412708 R26830 Hs.106137 ESTs, Weakly similar to CGHU7L collagen 3.23
441128 AA570256 ESTs, Weakly slmilarto T23273 hypothet 3.08
416902 AA375634 Hs.288974 hypothetical protein FLJ12528 2.56
402496 Target Exon 2.60
452817 AA322859 Hs.284275 Homo sapiens PAK2 mRNA, complete eds 2.54
437741 BE561610 Hs.5809 putative transmembrane protein; homolog 2.81
413753 U17760 Hs.75517 lamlnln, beta 3 (nlceln (125kD), kalinln 3.08
456977 AK000252 Hs.169758 hypothetical protein FLJ20245 3.22
419214 AI685324 Hs.89709 glutamate-cystelne llgase, modifier subu 2.73
446538 AV658957 Hs.135211 ESTs 2.52
454034 NM 000691 Hs.575 aldehyde dehydrogenase 3 family, member 3.76
419663 AA394208 Hs.92198 calcium-regulated heat-stable protein (2 3.03
413582 AW295647 Hs.71331 hypothetical protein MGC5350 3.14
424676 Y08565 Hs.151678 UDP-N-acetyl-alpha-D-galactosamlπe:polyp 2.63
427963 AI042582 Hs.181271 CGI-120 protein 2.52
428643 AA431383 Hs.98701 ESTs, Weakly similar to OSHU7B cytochrom 4.14
418329 AW247430 Hs.84152 cystathlonlne-beta-syπthase 2.52
434262 AF121858 Hs.12169 sorting nexln 8 2.50
446766 AF083208 Hs.16178 apoptosis antagonizing transcription fac 2.96
437879 BE262082 Hs.5894 hypothetical protein FLJ10305 3.10
444371 BE540274 Hs.239 forkhead box M1 3.68
401451 NM_004496*:Homo sapiens hepatocyte nude 2.64
433485 AI493076 Hs.306098 aldo-keto reductase family 1, member C2 3.79
435750 AB029012 Hs.4990 KIAA1089 protein 2.89 408901 AK001330 Hs.48855 hypothetical protein FLJ10468 2.54
418526 BE019020 Hs.8583B solute carrierfamlly 16 (monocarboxyllc 3.06
448633 AA311426 Hs.21635 tubuliπ, gamma 1 2.81
443715 AI583187 Hs.9700 cyclln E1 3.24
432441 AW292425 Hs.163484 Intron of hepatocyte nuclear factor-3 al 3.45
409041 AB033025 Hs.50081 Hypothetical protein, XP.051860 (KIAA119 2.96
420956 AA351584 Hs.100543 Homo sapiens clone 24505 mRNA sequence 2.73
428B44 AW972635 Hs.301904 hypothetical protein FLJ12671 2.90
404440 NM_021048:Homo sapiens melanoma antigen, 2.66
420186 NM 015925 Hs.95697 liver-specific bHLH-Zlp transcription fa 2.98
441031 AI110684 Hs.7645 flbrlπogen, B beta polypeptide 3.05
421307 BE539976 Hs.103305 Homo sapiens mRNA; cDNA DKFZp434B0425 (f 4.83
422605 H16646 Hs.118666 hypothetical protein PP591 2.78
409893 AW247090 Hs.57101 mlnlchromosome maintenance deficient (S. 2.64
440006 AK000517 Hs.6844 NALP2 protein; PYRIN-Contalnlng APAF1-II 3.69
453902 BE502341 Hs.3402 ESTs 2.60
424867 AI024860 Hs.153591 Not56 (D. melanogaster)-llke protein 3.62
450184 W31096 Hs.237617 Homo sapiens, clone IMAGE:3447394, mRNA, 2.50
422756 AA441787 Hs.119689 glycoprotein hormones, alpha polypeptide 3.42
408196 AL034548 Hs.43627 SRY (sex determining region Y)-box 22 2.65
428028 U52112 Hs.182018 lnterleukln-1 receptor-associated kinase 2.73
404996 Target Exon 2.54
414675 R79015 Hs.296281 Interleukin enhancer binding factor 1 2.78
429170 NM 001394 Hs.2359 dual specificity phosphatase 4 3.10
440590 AI863446 Hs.266308 mosaic serine protease 2.50
430316 NM 000875 Hs.239176 Insulln-llke growtli factor 1 receptor 2.59
430056 X97548 Hs.228059 KRAB-associated protein 1 2.59
448262 AW880830 Hs.186273 Homo sapiens qulescln Q6 (QSCN6) 3.89
414907 X90725 Hs.77597 polo (Drosophia)-like kinase 2.66
408116 AA251393 Hs.289052 Homo sapiens, Slmilarto RIKEN cDNA 5430 2.56
426283 NM 003937 Hs.169139 kynurenlnase (L-kynureπlne hydrolase) 4.59
454066 X00356 Hs.37058 calcltonln/calcltonln-related polypeptd 3.09
430508 AI015435 Hs.104637 ESTs 3.32
450663 H43540 Hs.25292 ribonuclease HI, large subunlt 2.97
442577 AA292998 Hs.163900 ESTs 2.73
453350 AI917771 Hs.61790 hypothetical protein FLJ23338 2.65
410444 W73484 Hs.132554 gb:zd54e04.s1 Soares_fetal_heart_NbHH19W 2.63
454057 AW009478 Hs.36574 hypothetical protein FLJ21125 3.07
430677 Z26317 desmoglein 2 2.62
440457 BE387593 Hs.21321 Homo sapiens clone FLB9213 PR02474 mRNA, 2.59
425811 AL039104 Hs.159557 karyopherin alpha 2 (RAG cohort 1, Impor 2.69
410151 X15723 Hs.59242 paired basic amino acid cleaving enzyme 2.70
420281 AI623693 Hs.323494 Predicted cation efflux pump 2.56
422880 AF228704 Hs.193974 glutathlone reductase 2.80
424494 U78575 Hs.149255 phospha.dyllnosltol-4-phosphate 5-klnas 2.62
457819 AA057484 Hs.35406 FLJ20522 Hypothetcal protein FLJ20522 2.77
440087 W28969 Hs.7718 hypothetical protein FLJ22678 2.64
424800 AL035588 Hs.153203 MyoD family inhibitor 3.02
412939 AW411491 Hs.75069 eukaryotic traπslaton elongation factor 3.23
442660 AW138174 Hs.130651 ESTs 2.52
440994 AI160011 Hs.272068 ESTs 3.34
432026 AA524545 Hs.224630 ESTs 2.70
429671 BE379335 Hs.211594 proteasome (prosome, macropain) 26S subu 2.75
428758 AA433988 Hs.98502 CA125 antigen; muc!n 16 4.09
429263 AAO19004 Hs.198396 ATP-blnding cassette, sub-family A (ABC1 4.29
426991 AK001536 Hs.214410 Homo sapiens cDNA FLJ10674 fis, clone NT 2.70
450998 BE387614 Hs.25797 splicing factor 3b, subunlt 4, 49kD 3.02
449207 AL044222 Hs.23255 nucleoporin 155kD 4.28
419897 X90826 Hs.93649 upstream transcription factor 2, c-fos I 2.59
457211 AW972565 Hs.32399 ESTs, Weakly similar to S51797 vasodilat 3.52
419667 AU077005 Hs.92208 a dislntegrin and metalloprotelnase doma 3.43
431083 AF110400 Hs.249200 fibroblast growth factor 19 2.93
427239 BE270447 ublquitin carrier protein 3.56
418164 AI761820 Hs.41074 ESTs, Weakly similar to I39294 McLeod sy 4.48
427528 AU077143 Hs.179565 mlnlchromosome maintenance deficient (S. 2.84
430375 AW371048 Hs.93758 H4 hlstone family, member H 3.26
457465 AW301344 Hs.122908 DNA replication factor 3.03
416000 R82342 Hs.79856 ESTs, Weakly simllarto S65657 alpha-1C- 3.21
420005 AW271106 Hs.133294 ESTs 3.53
425003 AF119046 Hs.154149 apurinIc/apyrimldiπic endonuclease(APEX 3.13
447033 AI357412 Hs.157601 Predicted gene: Eos cloned; secreted w/V 3.73
453439 AI572438 Hs.32976 guanine nucleotide binding protein 4 3.12
428865 BE544095 Hs.164960 BarH-like homeobox 1 3.74
417542 J04129 Hs.82269 progestagen-assoclated endometrial prate 3.56
414416 AW409985 Hs.76084 hypothetical protein MGC2721 2.72
435025 T08990 Hs.4742 anchor attachment protein 1 (Gaalp, yeas 2.55
419224 NM.012189 Hs.314452 flbrousheathln II 3.56
411975 AI916058 Hs.144583 3'UTR of: dead ringer (Drosophila)-llke 2.81
412856 BE386745 Hs.74631 basiglπ (OK blood group) 2.70
436887 AW953157 Hs.193235 hypothetcal protein DKFZp547D155 2.65
447289 AW247017 Hs.36978 melanoma antigen, family A, 3 3.12
410512 AA085603 Hs.250570 hypothetical protein MGC3180 2.69
453120 AA292891 Hs.31773 pregnancy-induced growth Inhibitor 3.76
440548 AL117408 Hs.7274 DKFZP434P1750 protein 3.15
444670 H58373 Hs.332938 hypothetical protein MGC5370 2.68
418478 U38945 Hs.1174 cyclln-dependeπt kinase Inhibitor 2A (me 4.85 421526 AL080121 Hs.105460 DKFZP564O0823 protein 2.72
414774 X02419 Hs.77274 plasminogen activator, uroklnase 3.51
447400 AK000322 Hs.18457 hypothetical protein FLJ20315 2.69
423063 BE159877 Hs.120824 hypothetical protein FLJ21845 2.61
432201 AI538613 Hs.298241 Transmembrane protease, serine 3 3.48
422976 AU076657 Hs.1600 chaperonln containing TCP1, subunlt 5 (e 2.78
435408 H07897 Hs.4302 ESTs, Weakly simllarto T29299 hypothet 3.29
418506 AA084248 Hs.85339 Unknown protein for MGC:29643 (formerly 2.61
422956 BE545072 Hs.122579 ECT2 protein (Epithelial cell transforml 3.61
429228 AI553633 hypothetical protein MGC33630 4,46
415214 AI445236 Hs.125124 EphB2 2.91
449281 AI808699 Hs.162717 hypothetical protein MGC15668 2.79
421305 BE397354 Hs.324830 dlptherla toxin resistance protein requl 2.52
437897 AA770561 Hs.146170 hypothetical protein FLJ 22969 3.10
425159 NM.004341 Hs.154868 carbamoyl-phosphate synthetase 2, aspart 3.15
445654 X91247 Hs.13046 thloredoxln reductase 1 3.98
408298 AI745325 Hs.271923 Homo sapiens cDNA: FLJ22785 fis, clone K 2.90
441362 BE614410 Hs.23044 RAD51 (S. cerevlslae) homolog (E coll Re 3.22
420029 BE258876 Hs.94446 polyamlne-modulated factor 1 2.68
408908 BE296227 Hs.250822 serine/threonlne kinase 15 2.65
442108 AW452649 Hs.166314 ESTs 3.36
424905 NM 002497 Hs.153704 NIMA (never in mitosis gene a)-related k 2.69
438552 AJ245820 Hs.6314 type I transmembrane receptor (seizure-r 2.83
450074 AI367213 Hs.14070 hypothetical protein FLJ14166 4.18
416322 BE019494 Hs.79217 pyrrollπe-5-carboxylate reductase 1 2.58
405770 NM_002362:Homo sapiens melanoma antigen, 2.71
424001 W67883 Hs.137476 paternally expressed 10 2.58
439963 AW247529 Hs.6793 platelet-activating factor acetylhydrola 3.01
424441 X14850 Hs.147097 H2A hlstone family, member X 2.63
410076 T05387 Hs.7991 ESTs 4.85
413142 M81740 Hs.75212 omlthiπe decarboxylase 1 2.58
448610 NM 006157 Hs.21602 nel (chlcken)-like 1 3.52
447960 AW954377 Hs.26412 ring finger protein 26 3.56
432415 T16971 Hs.289014 ESTs, Weakly slmilarto A43932 mucin 2 p 2.62
453905 NM.002314 Hs.36566 LIM domain kinase 1 3.30
437623 D63880 Hs.5719 chromosome condensation-related SMC-asso 2.58
453884 AA355925 Hs.36232 KIAA0186 gene product 2.87
427715 BE245274 Hs.180428 KIAA1181 protein 3.67
441553 AA281219 Hs.121296 ESTs 4.46
431070 AW408164 Hs.249184 transcriptoπ factor 19 (SC1) 2.87
421254 AK001724 Hs.102950 coat protein gamma-cop 2.59
451807 W52854 hypothetical protein FLJ23293 simllarto 2.99
411248 AA551538 Hs.69321 Homo sapiens cDNA FLJ14408 fis, clone HE 3.42
418054 NM 002318 Hs.83354 lysyl oxldase-llke 2 2.50
452259 AA317439 Hs.28707 signal sequence receptor, gamma (translo 2.56
423073 BE252922 Hs.123119 MAD (mothers against decapentapleglc, Dr 2.56
407792 AI077715 Hs.39384 putative secreted ligand homologous to f 2.60
432078 BE314877 Hs.24553 hypothetical protein FLJ12541 slmilarto 3.57
410553 AW016824 Hs.272068 hypothetical protein MGC14128 4.37
418113 AI272141 Hs.83484 SRY (sex determining region Y)-box 4 3.60
413063 AL035737 Hs.75184 chltnase 3-llke 1 (cartilage glycoprote 2.68
446557 U68566 Hs.15318 HS1 binding protein 2.60
416294 D86980 Hs.79170 KIAA0227 protein 2.71
452613 AA461599 Hs.23459 ESTs 2.67
431836 AF178532 Hs.271411 beta-site APP-cleavlng enzyme 2 2.53
417720 AA205625 Hs.208067 ESTs 2.58
438915 AA280174 Hs.285681 Williams-Beuren syndrome chromosome regl 3.95
429610 AB024937 Hs.211092 LUNX protein; PLUNC (palate lung and nas 7.69
409015 BE389387 Hs.49767 NM_004553:Homo sapiens NADH dehydrogenas 3.05
415279 F04237 Hs.1447 glial fibrillary acidic protein 4.05
448296 BE622756 Hs.10949 Homo sapiens cDNA FLJ14162 tis, clone NT 2.54
418960 NM 004494 Hs.89525 hepatorna-derived growth factor (HDGF) 2.54
446204 AI279809 Hs.150019 ESTs 2.81
413004 T35901 Hs.75117 Interleukin enhancer binding factor 2, 4 3.03
425944 AK000664 Hs.164256 hypothetical protein FLJ20657 2.62
425057 AA826434 Hs.1619 achaete-scute complex (Drosophila) homol 4.87
452461 N78223 Hs.108106 transcripton factor 2.61
453210 AL133161 Hs.32360 hypothetical protein FLJ10867 2.69
411825 AK000334 solute carrier family 39 (zinc transport 4.19
425234 AW152225 Hs.165909 ESTs, Weakly simllarto I38022 hypothet 3.15
437016 AU076916 Hs.5398 guanine monphosphate synthetase 3.68
407137 T97307 gb:ye53h05.s1 Soares fetal liver spleen 2.69
409757 NM.001898 Hs.123114 cystatin SN 3.47
444706 AK000398 Hs.11747 hypothetical protein FLJ20391 2.80
430393 BE185030 Hs.241305 estrogen-responsive B box protein 2.53
452838 U65011 Hs.30743 preferentially expressed anUgen In mela 6.17
447532 AK000614 Hs.18791 hypothetical protein FLJ20607 2.66
424140 Z48051 Hs.141308 myelln ollgodeπdrocyte glycoprotein 3.54
436217 T53925 Hs.107 fibrlnogen-llke 1 4.92
452833 BE559681 Hs.30736 KIAA0124 protein 3.80
422765 AW409701 Hs.1578 baculoviral IAP repeat-containing 5 (sur 2.90
443426 AF098158 Hs.9329 chromosome 20 open reading frame 1 3.20
409269 AA576953 Hs.22972 steroid 5 alpha-reduclase 2-like; H5AR g 4.09
422656 AI870435 Hs.1569 LIM homeobox protein 2 3.01
423551 AA32759B Hs.89633 ESTs 2.60
409187 AF154830 Hs.50966 carbamoyl-phosphate synthetase 1, mltoeh 4.21 409557 BE182B96 Hs.3686 ESTs 2.53
416984 H38765 Hs.80706 dlaphorase (NADH/NADPH) (cytochrome b-5 3.58
442173 N76101 Hs.8127 KIAA0144 gene product 2.77
408452 AA054683 Hs.192455 ESTs, Weakly similar to ALU7.HUMAN ALU S 4.18
428342 AI739168 Homo sapiens cDNA FLJ13458 fis, clone PL 2.79
426691 NM 006201 Hs.171834 PCTAIRE protein kinase 1 3.68
438956 W00847 Hs.135056 Human DNA sequence from clone RP5-850E9 3.56
456508 AA502764 Hs.123469 ESTs, Weakly slmilarto AF2088551 BM-01 2.93
449027 AJ271216 Hs.22880 dlpeptldylpeptldase III 2.95 0 431846 BE019924 Hs.271580 uroplakln 1B 3.78
419741 NM 007019 Hs.93002 ublqultin carrier protein E2-C 3.63
416361 AW204907 Hs.6872 ESTs, Weakly similar to CA13 HUMAN COLLA 2.94
407355 AA846203 Hs.193974 ESTs, Weakly similar to ALU1.HUMAN ALU S 2.60
424954 NM 000546 Hs.1846 tumor protein p53 (Ll-Fraumeni syndrome) 2.77
15 407754 AA527348 Hs.288967 Homo sapiens cDNA FLJ14105 fis, clone MA 3.20
419875 AA853410 Hs.93557 proenkephalin 3.46
413437 BE313164 Hs.75361 gene from NF2/menlngloma region of 22q12 2.54
417389 BE260964 Hs.82045 midklne (neurite growth-promoting factor 3.09
444381 BE387335 Hs.283713 hypothetical protein BC014245 2.80 0 453968 AA847843 Hs.62711 High mobility group (nonhlstone chromoso 5.29
427954 J03060 Hs.247551 metaxin 1 3.30
438746 AI885815 Hs.184727 Human melanoma-associated antigen p97 (m 2.57
422168 AA586894 Hs.112408 S100 calcium-binding protein A7 (psorias 2.73
425842 AI587490 Hs.159623 NK-2 (Drosophila) homolog B 3.17 5 448993 AI471630 KIAA0144 gene product 2.70
428004 AA449563 Hs.151393 glutamate-cysteine llgase, catalytc sub 2.69
425848 BE242709 Hs.159637 valyl-tRNA synthetase 2 3.79
424458 M29273 Hs.1780 myelln associated glycoprotein 2.69
419078 M93119 Hs.89584 Insullnoma-assoclated 1 5.07 0 430294 AI538226 Hs.32976 guanine nucleotide binding protein 4 2.82
429922 Z97630 Hs.226117 H1 hlstone family, member 0 2.52
409103 AF251237 Hs.112208 XAGE-1 protein 7.18
424629 M90656 Hs.151393 glutamate-cysteine llgase, catalytc sub 3.19
414313 NM 004371 Hs.75887 coatomer protein complex, subunit alpha 2.55 5 416138 C18946 Hs.79026 myeloid leukemia factor 2 2.50
434067 H18913 Hs.124023 Homo sapiens cDNA FLJ 14218 fis, clone NT 5.38
411908 L27943 Hs.72924 cytdlne deamlnase 3.32
428484 AF104032 Hs.184601 solute carrier family 7 (cationic amino 2.57
422095 AI868872 Hs.282804 hypothetical protein FLJ22704 2.83 0 430791 AA486293 Hs.272068 ESTs, Weakly similar to ALU3.HUMAN ALU S 3.14
428839 AI767756 Hs.82302 Homo sapiens cDNA FLJ14814 fis, clone NT 2.51
424481 R19453 Hs.1787 proteolipld protein 1 (Pelizaeus-Merzbac 2.66
447342 AI199268 Hs.19322 Homo sapiens, Simllarto RIKEN cDNA 2010 2.74
417900 BE250127 Hs.82906 CDC20 (cell division cycle 20, S. cerevl 3.04 5 411305 BE241596 Hs.69547 myelln basic protein 4.08
406690 M29540 Hs.220529 carcinoembryonlc anβgen-related cell ad 3.07
418738 AW388633 Hs.6682 solute carrierfamlly 7, (cationic amino 4.00
427344 NM 000869 Hs.2142 5-hydroxytryptamlne (serotonin) receptor 4.24
433447 U29195 Hs.3281 neuronal pentraxln II 2.98
50 419395 BE268326 Hs.90280 5-aminolmldazole-4-carboxamideribonucle 3.04
424420 BE614743 Hs.146688 prostaglandln E synthase 3.54
TABI E7B
55
Pkey: Unique Eos probeset identfler number
CAT number Gene cluster number Accession: Genbank accession numbers
60
Pkey CAT number Accession
. _ 450726 666520.1 AI732297 AW204600 T95017
65 421798 3042 4 BC017829 A 276646 AI984209 AA663933 AA634104 AA551528 AA634041 AA29B038 BG483990 T89297 BF853958 H64685 T90329
T60644 T57747 BF852694 T92529 BG482852 BF883064 BF883066 N74880 AA829796 N90716 454453 8582.4 BF313069 BE879305AW752781 AW752727 AW752559 AW752578AW752584 BF846118 AL545903BF846115AL525361
400245 12188.1 X79449 BC017853 AL121035 BF196384 AW119044 AI028023 AW451110 AI971911 A 015069 AI079170 AI376367 AI264113 AA829646
_n AA737579 AA449679 AA740864 NM 001111 U18121 AL567297 BG773801 BF973874 AV687104 AA527579 AA843525 BE706355
70 AI074589 AI523475 BE890249 AW406263 BE074258 AV729485 BF809610 BG058619 AA677244 BE179838 AA622264 AI460106
AA740411 AI499168 AI078223 AI682923 BE696559 AW375385 AA788739 BG984978 Z40874 T17054 F09669 AW844043 U10439 BI711870 AW245957 AU158567 AA679305 AA679316 W72510 AI346029 BG059762 AW251062 AA132373 AI925621 AI860230 AI340172 AW192891 AI707980 AI094937 AI042115 AI200901 BE328452 AA644678 AA551209 BE351065 AA970761 N68609 AW002028 AA160826 _ _ AI422774 AW873114 AW073597 AW664483 AI218710 AW020550 AW190607 AI984545 AI871921 AI333970 AI452887 AI818335 AA398655
75 AI554424 AI274187 BE465703 AW512940 AW241366 AI923954 AA576649 AW16B294 AA813181 AA912168 AI049738 AW514073
AA548255 AI569630 BE710031 AA244182 AI341697 AA563904 AI537990 AW517908 AW172943 Z39498 AI750294 AW150414 AI253293 BE825720 T31860 AW150775 D20310 AA150892 AU133933 BE781148 AL038957 BF910979 AA352297 BG988142 AW372175 BF229106 AW866705 BE093482 BG990396 AI499917 AA054452 H05484 AI828502 BM467331 AU140570 AL135417 BF947202 AW391926 BE813418 BF998473 T92021 BI021048 BM048783 AW501366 AW501342 AW501549 BE939021 BE707147 BE160974 BE305207 N49011 AA947119 80 AA678801 BE536876 AW897428 BG329648 BG818540 BE542344 BI919250 BI253018 AW130996 BE074249 BE895428 BI034862
BE083277BF952166 429978 35194 2 BE738425 BE738323 BM126944 AW629678 AW265195 AI916735 AI394255 AI573090 AI354442 AW612857 AI339558 AI919424 AI377532
AI354441 AI308821 AA772275 AW055215 AI589705 AI336532 AA806547 AV682125 H93575 AW071172 AW769904 AI863985 AW265018 AW196655 D79662 BE042393 N75017 AW014741 C75509 BE748621 H92431 AW079261 AW901780 AA329482 AW960115 BI260621 85 AI767525 R31663 BI918664 AW963196 C06195 AI678018 400213 D63478 NM 014847 BG756716 BG163437 BM463199 BG403203 AA401857 AA368774 AW408251 AL523107 BG026453 BF674703
AA604407 N29680 AA648135 AI288204 AI288200 AA594851 AI969057 BF033736 BI334216 BE925408 AI557055 BF328153 AI885038
AV743562 AW152023 AI678636 AI990677 AA911648 A1184369 AI830103 AA259120 AI924057 BG152397 AI695208 H71871 BI259526
T18975 BI259531 BF229650
447349 1063443.1 BE743847 AW809603 BM469626 AI375546 400203 11774 NM 002794 D26599 BM469989 BF305151 BG821966 BI089030 AW007738 Bl 222910 BM049422 BG028749 AI189162 AI831230
AW131497 BM272215 BE791105 AW778828 AA479594 AA480133 AA131997 AA284572 AA453009 BF928258 AA152127 AA393918
BF765307 BE247542 BF934697 BF341798 BE253409 AA470620 AI828932 AW379902 AV762678 AV741784 AV760892 AI025755
AA878562 AA630630 AA761708 AA862518 AA865831 AA862947 N53065 AA131821 AA293499 N23342 N26856 AI147346 AW951549
AA772963 BE245986 BG208493 AI8316668G474873 BI023168 AU149647 BG197069 BG191102 BF304178 BE536135 AA706900
AA443583 AI002710 AW276192 AU149842 BG214797 BG198193 AW197923 AW627799 T98663 BG194788 BG214656 BF345258
BG716363 AI066528 BI546220 AA393815 AA132004 AA353826 H97858 BG187823 BF841463 AI351714 AV735966 BG196439 BG216B40
BG198438 BG400762
456031 6000 2 BG469257 BM042651 AW772237 AI858055 AW043820 AI804955 AW028151 AI887909 AI582191 AI798900 AI299745 BF058971 BE504708
AW001777 BF000316 AW001248 AI336325 AI805058 AI923922 BM054790 AI949719 AI741492 AI684429 AI276119 AI269740 AI183994
AI719036 AA480650 AW263563 AI971175 AI347141 BF973966 AA480684 AI097473 AI580934 AI200633 BF058119 AW672804 AI348656
BF732192 AW517972 AI262960 M62028 N42455 BM050656 AA595104 AI074858 AA627913 AI304384 AW900999 AA365138 N66329
AI648474 AA642939 AI474817 AI054319 W25028 AA863058 BG469176 AA321296 BE778988 AI262696 BF026236 AW205513 AW594574
AA922438 W68465 BF684267 BF591011 AA367149 BG896411 AW243042 BI335118 BF915906 BF915905 BG338858 AI813670 AW819595
AW243178 AW819644 AW136076 AI810972 BF476651 AW515899 BE936236 BE905314 AI242330
406685 0.0 M18728 458748 701190.1 AI381530 BG942599 AW270510AW265104 415989 10194.1 BC013389 BC017398 AI023543 AA191424 AI267700 AI469633 AW958465 AW953397 AA172056 BE940298 BF909208 BF909980
BF095153 BG285837 AI720344 BF541715 AA355086 AA172236
441128 20932.1 BC014072 BE328850 AI356567 AI148171 AI022165 BG149661 BF000671 AA233101 AA573721 AA447991 AW016855 AI0O5068 AA554071
BF478215AA906902AW014761 BE905651 BE512923 BM047129 AA243852 AA232991 AA127550 AA127551 AA570256 AI473237
BF033706 N90525 AW973623 AI359627 BG674574 BE903322 430677 11749.1 NM 001943 Z26317 BG750290 BM043721 AW361908 BG494570 AW996792 BF915903 AW753487 BI335109 BE018413 BE874074
BF333555 BI016581 BI014002 BI015917 BE731644 BE927177 BE697899 BF999996 BF929423 BG951608 AW858747 AW858755
AW858760 AW858749 AW858751 AW363742 D58979 BE003946 AW858999 BG951830 AW859003 BF738953 AW369461 AW363740
AW998641 BG978975 BG015802 AW991316
427239 20459.2 AL532360 BE794750 AA582906 AI015067 AW271034 BG271636 AW075177 AW071374 AI345565 AI307208 BE138953 BE049086
AI334881 AWO75006 AW075181 AA464019 AW302733 AW075100 AW073433 AI802854 AI334909 AI802853 AI345036 AI348921 AI340734
AI307478 AI251289 AW302327 AW072520 AI312145 AW073656 AW072513 AW071289 AI307559 AA876186 T29587 AI307493 AI255068
AI252868 AI252839 AW074809 AI252926 AI252160 AI251662 AI251262 AI610913 AI270787 AI270156 A1252075 AW073469 AW072901
AW072496 AW071420 AI305762 AI254764 AI802837 A1251264 AW073049 AW071311 AI340643 BE138965 BE138502 AW073456
AI334733 AI054335 BE139260 AI054302 AI054060 AI054057 AI053722 AI289711 BE139228 AW470478 AW271039 AW302085 BE041872
AI254494 AI271496 AI252427 BF718773 BF718645 AW074866 BE857822
429228 215430.1 BG676155 BM009591 AI479075 A1025794 A1017967 AA448270 BE466812 AA853422 AI392649 BG952034 AA513384 BF840124 BE714620
AW969605 AI553B33
451807 17758.2 BM479185 AL552795 AL577722 BF038888 BM127617 BF510346 AW450652 AA865478 AW449519 BM127314 AI806539 AW449522
AA993634AI827626AA904788
411825 7891.1 AK000695 AK000489 BC001688 BG235988 AW006329 AI887644 AI207230 AI148213 AI304333 AI634653 AW662636 AI281247 AA946921
AA424487 BE272330 AI830588 AA159183 AA977141 BG231801 AA631793 AA975194 BF817537 AA477798 BI906631 AW083424
AA625199 NM.017767 AK000334 BF984048 AW815634 AL573992 AA430612 AA928390 AA464447 AW340827 AA424290 AI927759
BG951502 AW881353 BI765535
428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 AI928140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658
AA769094 BF446026 AW118719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704
AI356361 AI923640 AW070509 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311
AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 BI061872 BI059498 AA134476
AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166
448993 9350.1 BE734790 BE797215 BG759420 AW407710 BG325963 B1918794 BE278238 BI199200 BI518986 BI253338 BI262043 AW340858 BF375322
AI982791 AI567270 BF095628 BF095497 AI813332 BF766170 BF431658 R69173 AA454908 AA394063 AA346417 AA346416 D20284
AA053597 BI765427 BI819610 BM148877 AA293504 AA427705 AA399460 AA454833 AA292343 AA730380
TABLE 7C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers in this column are Genbank Identifier (GI) numbers. "Dunham I. et al." refers to the publication entted "The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495.
Strand: Indicates DNA strand from which exons were predicted.
NLpositlon: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLpositlon
401131 8699812 Minus 94802-94987,95804-95887,96323-96487,9759
402496 9797769 Minus 8615-9103
401451 6634068 Minus 119926-121272
404440 7528051 Plus 80430-81581
404996 6007890 Plus 37999-38145,38652-38998,39727-39872,4055
405770 2735037 Plus 61057-62075 Pkey Unique Eos probeset Identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene ttle
R1 90th percentile of lung metastases to the brain Als divided by the 90th percentile of lung adeπocarclπoma Als, where the 15th percentle of body tissue Als was subtracted from the numerator and denominator
SEQ ID N0(s) SEQ ID number(s) fornuclelc acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
425751 T19239 Hs 1940 crystallln, alpha B 2350 44
411305 BE241596 Hs 69547 myelin basic protein 2259 17
424481 R19453 Hs 1787 proteolipld protein 1 (Pelizaeus Merzbac 20 10 42
407100 R29657 gb F1-1179D 22 week old human fetal live 1212 6
454034 NM 000691 Hs 575 aldehyde dehydrogenase 3 family, member 730 82123
441899 AI372588 Hs 8022 TU3A protein 699 65
440747 AW297226 Hs 137840 ESTs, Moderately similar to SIX4.HUMAN H 650 62
445519 AI635202 Hs 170132 hypothetical protein FLJ22494 641 72
456940 H46986 Hs 31861 ESTs 604 83
424378 W28020 Hs 167988 neural cell adhesion molecule 1 589 41
412754 AW160375 Hs 74565 amyloid beta (A4) precursor-like protein 576
440889 R76274 Hs 28507 ESTs 567
415279 F04237 Hs 1447 gllal fibnllary acidic protein 561
449383 AW444712 Hs 196573 ESTs 553
424458 M29273 Hs 1780 myelin associated glycoprotein 540
419078 M93119 Hs 89584 Insuliπoma associated 1 536
409327 L41162 Hs 53563 collagen, type IX, alpha 3 510
425988 BE045897 Hs 53985 ESTs, Weakly similar to I38022 hypothet 505
412708 R26830 Hs 106137 ESTs, Weakly slmilarto CGHU7L collagen 497
405499 NM.020638* Homo sapiens fibroblast growt 475
426784 U03749 Hs 172216 chromogranin A (parathyroid secretory pr 475
454293 H49739 Hs 134013 ESTs, Moderately similar to H 61.HUMAN H 472
406536 Target Exon 463
424140 Z48051 Hs 141308 myelin ollgodendracyte glycoprotein 459
431846 BE019924 Hs 271580 uroplakin lB 457
422656 AI870435 Hs 1569 LIM homeobox protein 2 452
419875 AA853410 Hs 93557 proenkephalin 451
435504 W26415 gb 29c7 Human retina cDNA randomly pnme 450
435652 N32388 Hs 334370 uncharacteπzed hypothalamus protein HBE 449
404608 Homo sapiens cDNA FLJ 11027 fis, clone PL 447
440700 AW952281 Hs 296184 guanine nucleotide binding protein (G pr 447
409788 AW502154 Hs 57760 hypothetical protein FLJ23119, KIAA1790 446
404502 Target Exon 443
429401 AW296102 Hs 99272 ESTs, Weakly slmilarto S32567 A4 protel 441
425855 AF135025 Hs 159679 kallikrein 12 437
414215 BE262191 Hs 142003 ESTs 4 36
431934 AB031481 Hs 272214 STG protein 432
432351 AI270313 Hs 127762 hypothetical protein MGC12982 431
423011 NM.000683 Hs 123022 adrenergic, alpha 2C-, receptor 431
403233 C2001664* gl|9944235|emb|CAC05418 1| (AJ 428
402000 C17000761 gi|4506525]ref|NP 003952 1| rh 425
448677 AI560769 ESTs 422
433447 U29195 Hs 3281 neuronal pentraxln II 422
410028 AW576454 ESTs 4 19
404672 Target Exon 411
431083 AF110400 Hs 249200 fibroblast growth factor 19 407
424922 BE386547 Hs 217112 hypothetical protein MGC10825 406
416072 AL110370 Hs 79000 growth associated protein 43 400
414323 NM 014759 Hs 334688 KIAA0273 gene product 399
415314 N88802 Hs 5422 glycoprotein M6B 397
416340 N31772 Hs 79226 fasciculation and elongation protein zet 397
452023 AB032999 Hs 27566 KIAA1173 protein 396
407450 AJ006520 gb Homo sapiens mRNA for ml muscarinlc a 394
426344 H41821 Hs 322469 transcriptonal activator of the c fos p 392
436551 AI888055 Hs 34198 ESTs 391
422756 AA441787 Hs 119689 glycoprotein hormones, alpha polypeptde 389
425690 AW862317 Hs 47974 ESTs, Moderately similar to JC4969 pig c 388
427207 AF012131 Hs 173984 388
425057 AA826434 Hs 1619 achaete scute complex (Drosophila) homol 381
420320 AB002361 Hs 96633 KIAA0363 protein 378
406121 Target Exon 378
402356 C19000583* g!|7295202|gb|AAF50525 1| (AE 377
447028 AI973128 Hs 167257 brain link proteln-1 377
414063 H26904 Hs 75736 apollpoproteln D 376
423073 BE252922 Hs 123119 MAD (mothers against decapentapleglc, Dr 375
408748 J05500 Hs 47431 spectriπ, beta, erylhrocytc (Includes s 373
422357 AF016272 Hs 115418 cadherin 16, KSP-cadherln 373
449227 AJ403106 Hs 121824 ESTs 370
425450 U14755 Hs 157449 LIM homeobox protein 1 369
419555 AA244416 gb nc07d11 s1 NCI CGAP.P Homo sapiens 369
438944 AA302517 Hs 92732 KIAA1444 protein 368
433932 AW954599 Hs 169330 neuronal protein 366 413946 BE185066 Hs.2055 gb:MR1-HT0709-100500-002-c09 HT0709 Homo 3.65
406273 peptldylglyclne alpha-amidatπg moπooxyg 3.62
427993 AA418483 Hs.104806 ESTs 3.62
438743 AW664029 Hs.129496 ESTs 3.57
447868 AI434802 Hs.196071 ESTS 3.56
450875 AK000724 karyopherin alpha 6 (importin alpha 7) 3.55
457842 AJ251759 Hs.283846 Homo sapiens GNAS1 antisense transcript 3.54
404033 C5000413*:gi|202800|gb|AAA40703.1| (M647 3.54
423473 H49104 Hs.129888 hypothetical protein FLJ14768 3.53
446639 AI016826 Hs.342148 ESTs 3,51
421074 AI690321 Hs.203845 two pore potassium channel KT3.3 3.51
422440 NM 004812 Hs.116724 aldo-keto reductase family 1 , member B10 3.50
441030 AW204139 Hs.174424 ESTs, Weakly similar to para-amiπohlppur 3.50
421771 NM 001224 Hs.108131 caspase 2, apoptosls-related cystelne pr 3.50
423420 AI571364 Hs.128382 Homo sapiens mRNA; cDNA DKFZp761H224 (f 3.48
401980 Target Exon 3.46
400739 ENSP00000240971:Voltage-gated potassium 3.45
409915 AA701921 Hs.188436 ESTs 3.44
402560 NM_006610*:Homo sapiens mannan-blnding I 3.43
406939 M34515 gb:Human omega light chain protein 14.1 3.42
401670 Target Exon 3.41
420485 AF2185B6 Hs.288835 cell death-inducing DFFA-like effector b 3.40
414408 BE294783 Hs.279497 hypothetical protein MGC4638 3.39
435060 AI422719 Hs.120873 ESTs, Weakly similar to fork head like p 3.39
402206 Target Exon 3.37
435763 AI243929 ESTs 3.37
400307 AF005081 Homo sapiens skin-specific protein (xp32 3.37
429897 AA460370 Hs.103189 lipopolysaccharide specific response-68 3.34
413333 M74028 Hs.75297 fibroblast growth factor 1 (addle) 3.33
410939 AW811324 gb:IL3-ST0141-131099-017-A02 ST0141 Homo 3.32
433657 AI244368 Hs.1787 PH domain containing protein in retna 1 3.31
409702 AI752244 eukaryotic translation elongation factor 3.31
406131 Target Exon 3.31
455973 BE175424 gb:RC4-HT0578-170300-012-rJ01 HT0578 Homo 3.30
453169 AB037815 Hs.32156 KIAA1394 protein 3.30
415796 R87548 Hs.78854 ATPase, Na? transporting, beta 2 polypep 3.29
426039 BE265133 Hs.217493 annexln A2 3.28
419705 AW368634 Hs.154331 ESTs 3.27
416916 AW749469 Hs.61784 hypothetical protein FLJ14451 3.25
405326 Target Exon 3.25
420783 AI659838 Hs.99923 lectlπ, galactoside-binding, soluble, 7 3.24
418064 BE387287 Hs.83384 S100 calcium-binding protein, beta (neur 3.24
423869 BE409301 Hs.134012 C1q-related factor 3.23
436420 AA443966 Hs.31595 ESTs 3.23
444039 NM 016348 Hs.10235 chromosome 5 open reading frame 4 3.22
423897 AB033062 Hs.134970 DKFZP434N178 protein 3.22
452240 AI591147 Hs.61232 ESTs 3.21
407208 T10695 gb:hbc970 Human pancreatic Islet Homo sa 3.21
435538 AB011540 Hs.4930 low density llpoprotein receptor-related 3.21
454188 AW177809 gb;IL3-HT0059-180B99-007-C12 HT0059 Homo 3.20
408452 AA054683 Hs.192455 ESTs, Weakly slmilarto ALU7.HUMAN ALU S 3.20
423801 NM 015071 Hs.132942 GTPase regulator associated with the foe 3.19
458904 NM 012155 Hs.24178 mlcrotubule-associated protein like echl 3.19
440274 R24595 Hs.7122 scrapie responsive protein 1 3.18
414961 U27266 Hs.927 myosln-blnding protein H 3.18
421511 AA488940 Hs.105216 hypothetical protein FLJ11125 3.17
401478 Target Exon 3.17
451111 W96141 Hs.220687 ESTs 3.17
409275 F05689 Hs.269257 ESTs 3.17
440109 AK001138 Hs.333149 hypothetical protein FLJ 10276 3.16
406907 Z25427 gb:H.saplens proteln-seriπe/threoπlne ki 3.16
413166 BE068507 gb:MR1-BT0371-070500-010-c11 BT0371 Homo 3.15
455984 BE177442 gb:RC1-HT0595-200400-012-f01 HT0595 Homo 3.14
414463 T69078 Hs.76177 alpha-1-mlcroglobulln/blkuπin precursor 3.13
406535 Target Exon 3.13
430294 AI538226 Hs.32976 guanine nucleotide binding protein 4 3.13
423134 AJ012582 Hs.124161 hyperpolarizaton activated cyclic nu e 3.13
446598 AW250546 Hs.59317 gb:2821774.5prime NIH.MGC.7 Homo sapiens 3.12
422637 AA399024 Hs.118836 myoglobln 3.12
453439 AI572438 Hs.32976 guanine nucleotide binding protein 4 3.11
441251 BE010471 Hs.257747 ESTs 3.10
454453 AW752781 hypothetical protein FLJ12614 slmilarto 3.10
413570 BE158651 Hs.294022 hypothetical protein FLJ14950 3.09
424098 AF077374 Hs.139322 small praline-rich protein 3 3.08
403437 C3001181*:gi|12O52997|emb|CAB66673.1| (A 3.08
458579 AI241355 Hs.334604 Homo sapiens mRNA for KIAA1870 protein, 3.08
453991 AW014915 Hs.273741 ESTs 3.07
431912 AI660552 ESTs, Weakly similar to A56154 Abl subst 3.06
401826 Target Exon 3.06
410022 AA079727 gb:zm20e09.r1 Stratagene pancreas (93720 3.05
420262 AW964073 Hs.58362 hypothetcal protein FLJ12681 3.05
431917 D16181 Hs.2868 peripheral myelln protein 2 3.04
448389 AW188950 Hs.345838 ESTs 3.04
428830 AC002115 Hs.194061 ets variant gene 2 3.03
447414 D82343 Hs.74376 neuroblastoma (nerve tissue) protein 3.02
407168 R45175 Hs.117183 ESTs 3.02 422010 AA302049 Hs.31181 Homo sapiens cDNA: FLJ23230 fis, clone C 3.02
448191 NM 005881 Hs.20644 branched chain alpha-ketoacid dehydragen 3.02
458963 AI701393 Hs.278728 Rad and Gem-related 2 (rat homolog) 3.01
402409 Target Exon 3.00
421048 AI821593 Hs.186669 ESTs 3.00
417697 R09609 Hs.193118 ESTs 3.00
433951 AW274301 Hs.165384 ESTs 3.00
411908 L27943 Hs.72924 cytdlπe deamlnase 3.00
444828 AI198680 gb:qf51f02.x1 SoaresJestis.NHT Homo sap 2.99
451619 AA018854 glutathlone peroxidase 3 (plasma) 2.98
423515 AA327017 Hs.176594 ESTs 2.96
441134 W29092 Hs.346950 cellular retinolc acid-binding protein 1 2.95
446204 AI279809 Hs.150019 ESTs 2.95
431677 AK000496 Hs.306989 hypothetical protein FLJ20489 2.94
434859 BE255080 Hs.299315 collapsln response mediator proteIn-5; C 2.94
402220 C19000596*:gl|6755546|ref|NP_036107.1| s 2.94
453629 BE179903 gb:l 3-HT0618-110500-133-F09 HT0618 Homo 2.93
443219 AI354669 Hs.187461 ESTs, Weakly simllarto C29149 prollne-r 2.93
413248 T64858 Hs.26966 hypothetical protein DKFZp547J036 2.93
434067 H18913 Hs.124023 Homo sapiens cDNA FLJ14218 fis, clone NT 2.93
400840 Target Exon 2.93
404381 Target Exon 2.93
424340 AA339036 Hs.7033 ESTs 2.93
415651 AI207162 Hs.3815 stathmln-llke-prateln RB3 2.91
447103 AI361877 Hs.270564 ESTs, Weakly simllarto pro alpha 1(1) c 2.91
453120 AA292891 Hs.31773 pregnancy-Induced growth Inhibitor 2.91
456454 T90789 Hs.94308 RAB35, member RAS oncogene family 2.90
424306 AI863322 Hs.192985 ESTs, Weakly similar to Kl AA0227 [H.sapi 2.89
449792 AI568508 Hs.239444 ESTs, Weakly slmilarto JC5963 stable tu 2.88
408726 BE046452 Hs.255739 ESTs, Weakly simllarto Z205.HUMAN ZINC 2.88
443906 AA348031 Hs.7913 ESTs 2.87
418828 AF020774 Hs.88844 Homo sapiens hair and skin epidermal-typ 2.87
425287 R88249 Hs.155524 peanut (Drosophlla)-like 2 2.86
420767 AF072711 Hs.99918 carboxyl ester llpase (bile salt-stlmula 2.86
417390 AA196552 Hs.85852 hypothetical protein MGC3169 2.85
437595 AI028309 Hs.114246 ESTs 2.85
419663 AA394208 Hs.92198 calcium-regulated heat-stable protein (2 2.84
406320 Target Exon 2.84
452263 AA025116 Hs.33333 ESTs 2.83
433472 AI541246 Hs.3343 phosphoglycerate dehydrogenase 2.83
420751 J03019 Hs.99913 adrenergic, beta-1-, receptor 2.83
454066 X00356 Hs.37058 calcitonin/calcltonln-related polypeptld 2.82
437926 BE383605 Hs.300816 small GTP-blndlng protein 2.81
406881 D16154 gb:Human gene for cytochrome P-450c11, e 2.81
437745 AI381515 Hs.158381 ESTs 2.80
425939 AK001527 Hs.163953 hypothetical protein FLJ10665 2.80
407375 AA091354 gb:IIOB15.εeq.F Human fetal heart, Lambd 2.80
427344 NM 000869 Hs.2142 5-hydroxytryptamine (serotonin) receptor 2.79
430393 BE185030 Hs.241305 estrogen-responsive B box protein 2.79
434607 R70848 Hs.163568 ESTs 2.78
401940 Target Exon 2.78
427693 BE546832 Hs.180370 cofilin 1 (non-muscle) 2.78
429487 M13077 Hs.284255 alkaline phosphatase, placental (Regan I 2.77
413662 BE155866 Hs.25522 KIAA1808 protein 2.77
451179 W05469 Hs.31818 ESTs 2.77
444643 AW450739 Hs.28077 GDP-mannose pyrophosphorylase B 2.77
401504 Target Exon 2.77
407570 Z19002 Hs.37096 zinc finger protein 145 (Kruppel-llke, e 2.77
453830 AA534296 Hs.20953 ESTs 2.76
428342 AI739168 Homo sapiens cDNA FLJ13458 fis, clone PL 2.76
440548 AL117408 Hs.7274 DKFZP434P1750 protein 2.76
433879 AA613312 Hs.291798 ESTs 2.76
416530 U62801 Hs.79361 kalllkrein 6 (neuroslπ, zyme) 2.76
404224 Target Exon 2.75
409836 AA077964 gb:7H12A01 Chromosome 7 HeLa cDNA Llbrar 2.75
443665 AV646058 Hs.282325 ESTs 2.74
431932 AB015349 Hs.22361 Homo sapiens HRIHFB2063 mRNA, partial cd 2.74
429545 AI824164 lymphocyte antigen 6 complex, locus E 2.74
406979 M85247 gb:H.saplens dopamlne D1A receptor gene, 2.74
444506 AI159863 Hs.143713 ESTs 2.74
419727 AW160796 Hs.92700 DKFZP5640243 protein 2.74
409557 BE182896 Hs.3686 ESTs 2.73
452309 AW206836 Hs.224491 ESTs 2.73
435814 AW615179 Hs.152870 ESTs 2.73
442926 AW014374 Hs.144849 ESTs 2.73
454360 L78207 Hs.54470 ATP-blndlng cassette, sub-family C (CFTR 2.72
425547 AA359181 gb:EST68183 Fetal lung II Homo sapiens c 2.72
427587 BE348244 Hs.284239 ESTs, Weakly slmilarto I78885 serine/th 2.72
421871 AK001416 Hs.306122 glycoprotein, syπaptc 2 2.71
448045 AJ297436 Hs.20166 prostate stem cell antigen 2.71
442257 AW503831 Human EST clone 25267 mariner transposon 2.71
441834 AL138034 Hs.7979 KIAA0736 gene product 2.71
425211 M18667 Hs.1867 progastricslπ (pepslπogen C) 2.71
447128 AI271898 cyclin K 2.70
408115 AB033107 Hs.42796 KIAA1281 protein 2.70
407394 AF005081 gb:Homo sapiens sklπ-speclfic protein (x 2.70 445570 AW239531 Hs.102367 HMG-box transcription factor TCF-3 2.70
405060 Target Exon 2.70
403016 C21000452*:gl|7657283|ref|NP_056623.1| k 2.68
420037 BE299598 Hs.135569 hypothetical protein FLJ14708 2.68
401007 ENSP00000227594*:FLJ00043 protein (Fragm 2.67
423942 AF209704 Hs.169407 glycollpld transfer protein 2.67
453210 AL133161 Hs.32360 hypothetical protein FLJ10867 2.67
429259 AA420450 Hs.292911 Plakophilin 2.67
400524 Target Exon 2.66
453017 R84301 Hs.31387 DKFZP564J0123 protein 2.66
414213 BE297765 gb:601176246F1 NIH.MGC.17 Homo sapiens c 2.66
416056 H18056 Hs.6829 Homo sapiens mRNA for KIAA1644 protein, 2.65
438245 AL137688 Hs.6132 coplne VI (neuronal) 2.65
425256 BE297611 Hs.155392 collapsln response mediator protein 1 2.65
416413 H53930 Hs.35354 ESTs 2.65
412595 AA113749 gb:zn66d07,rt Stratagene HeLa cell s393 2.65
428439 BE467359 Hs.24986 ESTs 2.65
411830 BE549420 Hs.173497 Sec23 (S. cerevlslae) homolog B 2.64
417343 AA197132 Hs.231581 myosln, heavy polypeptide 1, skeletal mu 2.64
447582 BE293520 Hs.18910 prostate cancer overexpressed gene 1 2.64
427627 R87582 Hs.179915 guanine nucleotide binding protein (G pr 2.64
417852 AJ250562 Hs.82749 transmembrane 4 superfamlly member 2 2.63
446924 AW134643 EST 2.63
429024 AI652297 Hs.119302 complementclq tumor necrosis factor-ret 2.62
407846 AA426202 Hs.40403 Cbp/p300-lnteractng traπsactlvator, wit 2.62
426328 AW631296 Hs.123933 gb:hh83c09.y1 NCI.CGAP.GU1 Homo sapiens 2.62
400789 C11001367*:gl|1076205|plr||S50754 hypoth 2.61
402792 Target Exon 2.61
400655 Target Exon 2.61
401496 Target Exon 2.60
401663 Target Exon 2.60
431056 BE616373 Hs.249163 fatty acid hydroxylase 2.60
407027 U63312 gb:Human cosmld LL12NC01-242E1, ETV6 gen 2.60
412659 AW753865 Hs.74376 olfactomedln related ER localized protel 2.60
422927 AW247388 Hs.301423 calcium binding protein 1 (calbraln) 2.59
409108 AA339443 Hs.48793 sialyltransferase 6 (N-acetyllacosaminld 2.59
425001 U55184 Hs.154145 hypothetical protein FLJ 11585 2.59
457131 AC002310 Hs.301463 Human Chromosome 16 BAG clone CIT987SK-A 2.59
432941 W04803 Hs.279851 hypothetical protein FLJ10241 2.59
416889 AW250318 Hs.80395 mal, T-cell differentiation protein 2.59
437800 AA897636 Hs.159366 ESTs 2.58
401815 Target Exon 2.58
423849 AL157425 Hs.133315 Homo sapiens mRNA; cDNA DKFZp761J1324 (f 2.58
419272 AA663904 Hs.89862 TNFRSF1 A-assocIated via death domain 2.58
402978 Target Exon 2,57
428931 AA994979 Hs.98967 ATPase, H()-transportng, lysosomal, non 2.57
444613 H29627 Hs.79092 hypothetical protein FLJ14427 2.57
441087 AI797588 ESTs 2.57
409870 AW502321 gb:UI-HF-BROp-a]s-e-05-0-Ul.r1 NIH_MGC_5 2.57
438870 AF075011 gb:Homo sapiens full length Insert cDNA 2.57
439340 AB032436 Hs.6535 brain-specific Na-dependent Inorganic ph 2.56
439671 AW162840 Hs.6641 kinesin family member 5C 2.56
439285 AL133916 hypothetical protein FLJ20093 2.56
407561 BE313226 Hs.94761 KIAA1691 protein 2.56
423118 AL035460 Hs.124009 Human DNA sequence from clone RP5-860F19 2.56
435406 F26698 Hs.4884 calcium/calmodulin-dependent protein kin 2.56
442660 AW138174 Hs.130651 ESTs 2.55
403649 Target Exon 2.55
450493 M93718 Hs.166373 nitric oxide synthase 3 (endothelial eel 2.55
424463 AW195353 Hs.119903 ESTs 2.54
432201 AI538613 Hs.298241 Transmembrane protease, serine 3 2.54
401915 Target Exon 2.54
439796 AI566839 Hs.124483 ESTs 2.54
433091 Y12642 Hs.3185 lymphocyte antigen 6 complex, locus D 2.54
448555 AI536697 Hs.159863 ESTs 2.54
429712 AW245825 Hs.211914 ENSP00000233627*:NADH-ubiqulπone oxldore 2.54
455145 AW858396 Hs.208680 ESTs 2.54
431463 X95632 Hs.343575 abl-lnteractor 12 (SH3-coπtalning protei 2.53
440545 AW183201 Hs.190559 ESTs 2.53
413865 AA132816 Hs.151714 Homo sapiens mRNA for KIAA1769 protein, 2.53
406312 Target Exon 2.53
428366 AI803651 Hs.191608 ESTs 2.52
417823 R8B869 Hs.102447 TSC-22-like 2.52
429211 AF052693 Hs.198249 gap Junction protein, beta 5 (connexln 3 2.52
413140 T06607 Hs.6846 hypothetical protein FLJ13055 2.52
424342 AF131778 Hs.145432 similar to PSD-95/SAP90-associated prate 2.52
447823 AI432628 Hs.80887 v-yes-1 Yamaguchl sarcoma viral related 2.52
404807 Target Exon 2.51
417998 AW967420 gb:EST379495 MAGE resequences, MAGJ Homo 2.51
426600 NM.003378 Hs.171014 VGF nerve growth factor Inducible 2.51
420259 AF004884 Hs.96253 calcium channel, voltage-dependent, P/Q 2.51
402201 C1900028B*:gl|7209634|dbJ|BAA92285.1| (A 2.51
451698 Y16187 Hs.26880 endothellπ converting enzyme-like 1 2.50
447786 BE620810 Hs.39619 hypothetical protein LOC57333 2.50
459081 W07808 Hs.141662 ESTs, Weakly similar to ALU1.HUMAN ALU S 2.50
423063 BE159877 Hs.120824 hypothetical protein FLJ21845 2.50 TABLE 8B
Pkey: Unique Eos probeset identifier number
CAT number: Gene cluster number
Accession: Genbank accession numbers
Pkey CAT number Accession
435504 45952.3 W26415 BI041755 BI040636 AA683081 BF954853 BF964120 BF848451 BE143889 BF827761 AW899337 AW899594 BF947312 448677 6343181 AI560769 AI857497 AW151454 410028 958086.1 AW576454 AW576456 AW576435 407450 7399.1 BC022984 BC007740 AF385587 NM 000738 AL536991 AL537084 AI500293 AI685922 AI821510 AI791651 AW451282 AJ006520 BI757352
BI913662 BI197683 BI755888 BI913560 BF315022 H19732 AL566641 AL566592 AI202576 AA531511 BF313917 BI198135 BG820557
419555 252042.1 AA244401 AA244416 450875 10801.1 AL041364 BE393266 AA573189 BF589066 AI623423 AI889612 H54292 AA085863 AA669816 BE542832 BI094274 AI360690 T61853
AW081194AI541147 AW750358
435763 1356001 AA699940 AI243929AA777255 400307 27110.2 AF005081 BG193848 410939 1064852.2 AW811332AW811335 AW811328AW811329AW811339 409702 383881 AK056951 AK026458 BI439120 BM021106 F30243 BM055214 BM054962 BM069667 F37401 AA563621 AI752243 AI720773 AI933014
F18964 F35317 F35258 F27772 H39537 AW445222 F19408 H28557 F30608 F31797 F30960 BF837737 BF837688 AL551046 BI758668
BI765038 BI837440 BE392882 BI438801 AI093511 AI752244 AI784111 BG490221 BF338840 BF338974 BG896472 AL576843 AW966769
F25388 F37436 H28558 AI025548 AA782333 F30929 F36002 F21229 AI720539 AA719449 F21231 F18924 AA626886 F30774 F27704
F31411 F31127F33381 F36153 F31793 F31138 F31966 F33901 AA298244 BI757347 AI810201 AI692843 F29441 H51409F21804
AW973249 F18440 F17572 F32499 AA327152 AA534140 AI188088 F18893 F23362 AA010888 F18143 Z28500 H27651 AI720790 F22425
H13178 H28677 F21098 F37777 F21466 F16598 F23420 AL574723 R75610 F34035 F17845 F18560 F25902 R79117 F35534 F15713
AI612800 F16563 F15645 F33609 F29995 BG939623 F17385 F17384 F18660 F17922 F15523 AI093253 F18359 F31452 F00232 AI583430
BM021353 AA284108 H27650 H29935 BE708208 AA010737 H51451 Z19399 AI678418 AI952535 F17265 F17826 F37939 F35639 F17367
W75962 R70189 Z28755 R72106 AA335915 R75700 R79116 W72887 AI581552 R71403 F23388 C03913 BI75614981116109 BF790727
AL553994 R82966 W47487 AA456066 AW984608 BE708220 BG490537 W47419
455973 1561647.1 BF352282 BE175424 BE175418 BE175383 454188 645555.1 R81094AW177908AW177809 413166 1492542.1 BE068443 BE068507 BE068731 BE068509 BE068511 BE068728 BE068636 BE068633 BE068695 BE068730 BE068322 BE068510
BE068581 BE068518 BE068779 BE068397 BE068515 BE068333
455984 15632391 BE177445 BE177448 BE177440 BE177433 BE177439 BE177444 BE177442 454453 8582.4 BF313069 BE879305 AW752781 AW752727 AW752559 AW752578 AW752584 BF846118 AL545903 BF846115 AL525361 431912 610.10 BI763666 BI517886 B1759051 AI688604 AI660552 BF588523 AW004785 AW295479 BF591117 BF002672 BF064073 AA594441 AI380340
AI700219 AI659950 AI688540 AW296326
410022 2576815.1 AA824267 AA079728 AA079727 444828 2816194.1 AI919288 AI824969 AI824982 AI198680 451619 58817.2 AB067501 BE168197 AA477760 BF365805 AI658698 AI420374 AW006448 BE168079 BE179882 BF352503 AW850126 AI902617 AI344041
AI805642 BG914033 BE710337 F01902 H08649 BE180351 BE047272 R46826 AA897207 BE180115
453629 29513.2 BG772130 BF928490 BI559843 BF755758 BF905496 BG718616 BG899602 BG772217 BG719694 BI767332 AL046349 BI005797
BE179903
428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 AI928140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658
AA769094 BF446026 AW11B719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704
AI356361 AI923640 AW070509 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311
AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 BI061872 BI059498 AA134476
AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166
409836 25104981 AA077964 AA768182 AA077813 429545 934.5 BG678726 BG708995 AI823645 AI669787 AI676005 AA456229 BF475367 BM021242 AW129612 BF109992 AI298273 AI823860 AI804012
AI824164 AA773987 W96164 BM021522 AI825903 AI824295 AA454622 BE833075 AW883986 BE833189 AI264049 AI090237 AI306153
BF941075 BF369872 AW884073
425547 12282331 AW963016AA359181 AA359849 442257 18892.1 AK055924 BC014104 BE889267 BI546677 BI549386 AL596984 AW503317 AW503831 BE410616 BI600938 BI560459 BG980827 447128 11028.3 BG292064 AI452509 AI271898 BE048502 BI966153 X84721 AI858001 BM021943 AI553937 AI765259 F25787 AW015380 AA554539
AW059537 F35749 AA149853 AA961610 AI568815 AW973696 C00201 R77127 BG438065 AI244810 H00719
407394 27110.2 AF005081 BG193848 414213 5112.13 BF311061 BG828926 BE262061 BI199425 T83915 AL554295 BG830004 BI33509781193093 BF823498 BF823472 BM193195 AI952524
BF768990 BE781389 BI193044 BE297765
412595 35761 2 AW964908 AA1137498F907463 AA325520 BF911645 BF923879 BF928243 446924 626737.1 AI694696 BE328826 BE504314 AI457297 AW134643 AI348387 441087 2642272 1 AI797588 AI357156 AI204430 AA916498 409870 917085.1 AW502321 AW502965 AW502314 AW502455 AW502282 AW502800 438870 52141.1 AF075011 R63414 R63365 439285 22495.1 AF086101 AL133916 AW955684 AW950828 AI346341 AI867454 BM263376 BF432231 AI421279 AI655270 AW014882 BF439949
AA775552 N62351 AA626243 N59253 AI341407 AA456968 AA457077 AI358918 AA364013 N79113 N54784 BE175639 N76721 AV727392
Z45529 Z44343 F05908 F05403 F05398
417998 250632.1 AW967420 AA210915 AA236991 AA210916 TABLE8C
Pkey: Unique numbercorrespondlng to an Eos probeset
Ref: Sequence source. The 7 digit numbers In this column are Genbank Identifier (GI) numbers. "Dunham I. et al." refers to the publication entted "The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495. Strand: Indicates DNA strand from which exons were predicted. NLpositlon: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLposlton
405499 5762548 Plus 124845-125055,131730-131833 406536 7711478 Plus 25655-25782
404608 9588566 Minus 22507-22637,28093-28397
404502 7229863 Minus 56277-56819
403233 7637801 Plus 171338-171464,172980-173099
402000 3935221 Plus 3935-4083,7733-7845,14982-15082
404672 9797204 Minus 24463-24607,24711-24852,25429-25565
406121 9143818 Plus 322375-323091
402356 8886972 Minus 90528-91265
406273 7543785 Plus 28641-29291
404033 8122195 Plus 7976-8156
TABLE 9A Ahnut 252 genes downregulated In lung metastases to the brain relative to primary lung tumors
Pkey Unique Eos probeset identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene tte
R1 90th percentile of lung adenocarclnoma Als divided by the 90lh percentle of lung metastases to the brain Als, where the 15th percentle of all normal body tissue Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID
417204 N81037 Hs 1074 surfactant, pulmonary associated protein 3927 125
418026 BE379727 Hs 83213 fatty acid binding protein 4, adlpocyte 2094 27
424206 NM 003734 Hs 198241 amine oxldase, copper containing 3 (vase 1897 40102
410677 NM 003278 Hs 65424 tetranectn (plasmlnogen binding protein 771 1691
435684 NM 001290 Hs 4980 LIM domain binding 2 11 20 61 114
415162 AF035718 Hs 78061 transcription factor 21 662 2293
409385 AA071267 gb zm61g01 r1 Stratagene fibroblast (937 8 15 14
407694 U77594 Hs 37682 retinolc acid receptor responder (tazaro 11 84 9 87
441835 AB036432 Hs 184 advanced glycosylation end product sped 839 64116
453655 AW960427 Hs 342874 transforming growth factor, beta recepto 425 80
415274 AF001548 Hs 78344 myosln, heavy polypeptide 11, smooth mus 1732
412047 AA934589 Hs 49696 ESTs 627
423778 Y09267 Hs 132821 flavin containing monooxygenase 2 736
407744 AB020629 Hs 38095 ATP binding cassette, sub family A (ABC1 987
429350 AI754634 Hs 131987 ESTs 541
410016 AA297977 Hs 57907 small Inducible cytokine subfamily A (Cy 1030
407245 X90568 Hs 172004 tltln 433
426752 X69490 Hs 172004 tltln 415
431723 AW058350 Hs 16762 Homo sapiens mRNA, cDNA DKFZp564B2062 (f 576
428043 T92248 Hs 2240 uteroglobln 703
435146 R44557 Hs 23748 ESTs 496
416950 AL049798 Hs 80552 dermatopontln 11 09
441281 BE501247 Hs 144084 ESTs 642
404246 Target Exon 616
430998 AF128847 Hs 204038 Indolethylamine N methyltransferase 485
417355 D13168 Hs 82002 endothelin receptortype B 424
438150 AA037534 Hs 342874 transforming growth factor, beta recepto 417
453676 AW853745 Hs 286035 hypothetical protein FLJ22686 761
422550 BE297626 Hs 296049 mlcrofibπllar associated protein 4 537
422667 H25642 ESTs 640
423007 AA320134 Hs 196029 Homo sapiens mRNA for KIAA1657 protein, 469
420225 AW243046 Hs 282076 Homo sapiens mRNA for KIAA1650 protein, 460
424027 AW337575 Hs 201591 ESTs 434
453180 N46243 Hs 110373 ESTs, Highly similar to T42626 secreted 515
443062 N77999 Hs 8963 Homo sapiens mRNA full length Insert cDN 461
459247 N46243 Hs 110373 ESTs, Highly similar to T42626 secreted 455
451154 AA015879 Hs 33536 ESTs 486
438873 AI302471 Hs 124292 Homo sapiens cDNA FLJ23123 fis, clone L 990
456898 NM.001928 Hs 155597 D component of complement (adlpsln) 365
418058 AW161552 Hs 83381 guanine nucleotide binding protein 11 347
410066 AL117664 Hs 58419 DKFZP586L2024 protein 426
429640 U83508 Hs 2463 anglopoietn 1 536
430488 NM 004673 Hs 241519 anglopoletn like 1 339
410023 AB017169 Hs 57929 silt (Drosophila) homolog 3 384
420105 AW015571 Hs 32244 ESTs, Weakly slmilarto FMOD.HUMAN FIBRO 662
410545 U32324 Hs 64310 Interleukin 11 receptor, alpha 499
412002 AA913024 Hs 84698 Homo sapiens cDNA FLJ14300 fis, clone PL 447
444561 NM 004469 Hs 11392 c-fos Induced growth factor (vascular en 351
425764 AW996009 Hs 112572 Homo sapiens cDNA FLJ14130 fis, clone MA 437
408741 M73720 Hs 646 carboxypeptdase A3 (mast cell) 532
418947 W52990 Hs 22860 ESTs 573
419111 AA234172 Hs 137418 ESTs 696
447371 AA334274 Hs 18368 DKFZP564B0769 protein 778
416030 H15261 Hs 21948 ESTs 398
423690 AA329648 Hs 23804 ESTs, Weakly similar to PN0099 son3 prot 332
412810 M21574 Hs 74615 platelet-derived growth factor receptor, 549
413474 T86312 Hs 334485 Homo sapiens cDNA FLJ14438 fis, clone HE 727
439335 AA742697 Hs 62492 NM.052863 Homo sapiens εecretoglobln, fa 516
425498 AL096725 Hs 289010 DKFZP434B103 protein 576
445516 R50291 Hs 10846 ESTs, Weakly simllarto JH0783 dlamine N 870
420626 AF043722 Hs 99491 RAS guanyl releasing protein 2 (calcium 439
416585 X54162 Hs 79386 lelomodin 1, smooth muscle (LMOD1) (Thy 340
427164 AB037721 Hs 173871 KIAA1300 protein 482
426488 X03350 Hs4 alcohol dehydrogenase 1B (class I), beta 370
414290 AI568B01 Hs 71721 ESTs 441
417967 BE244373 Hs 1119 nuclear receptor subfamily 4, group A, m 416
451245 AA016218 Hs 58231 ESTs 445
418807 NM 004944 Hs 88646 deoxyribonuclease I like 3 4 27
406923 S70622 gb G1 phase-specific gene (3' region) [h 349
420556 AA278300 Hs 124292 Homo sapiens cDNA FLJ23123 fis, clone L 819
441499 AW298235 Hs 101689 ESTs 557
443577 AI078033 Hs 177170 ESTs, Weakly similar to ALU8 HUMAN ALU S 494 420174 AI824144 Hs 199749 ESTs 5 14
454072 AW572954 Hs 252851 ESTs 349
422195 AB007903 Hs 113082 KIAA0443 gene product 467
411988 AA455459 Hs 164480 ESTs, Weakly slmilarto T50609 hypotheϋ 545
414577 AI056548 Hs 72116 hypothetical protein FLJ20992 similar to 363
441723 R72137 Hs 7949 DKFZP586B2420 protein 464
425887 AL049443 Hs 161283 Homo sapiens mRNA, cDNA DKFZp586N2020 (f 407
447081 Y13896 Hs 17287 potassium Inwardly-rectifying channel, s 381
453355 AW295374 Hs 31412 myopodin 337
458504 AW070634 Hs 144794 ESTs 436
435823 R07856 Hs 16355 ESTs 328
415386 Z43087 gb HSC13A121 normalized Infant brain cDN 332
448274 AI268097 Hs 67317 Homo sapiens cDNA FLJ11775 fis, clone HE 380
425622 AW360847 Hs 16578 ESTs 366
418965 AI002238 Hs 11482 splicing factor, argiπlπe/seπne-rich 11 556
450696 AI654223 Hs 16026 hypothetical protein FLJ 23191 386
447742 AF113925 Hs 19405 caspase recruitment domain 4 440
413802 AW964490 Hs 32241 ESTs, Weakly slmilarto S65657 alpha 1C 361
431971 BE274907 Hs 77385 myosln, light polypeptide 6, alkali, smo 419
455653 BE154075 gb PMO HT0339 200400 010 E05 HT0339 Homo 529
406760 AA829363 gb Of08g04 s1 NCI_CGAP_Co12 Homo sapiens 356
443932 AW888222 Hs9973 tensln 368
421341 AJ243212 deleted In malignant brain tumors 1 475
432485 N90866 Hs 276770 CDW52 antigen (CAMPATH-1 antigen) 375
411962 AA099050 gb zk85d12 r1 Soares_pregπanLuterus_NbH 443
453874 AW591783 Hs 36131 collagen, type XIV, alpha 1 (uπdulln) 505
444769 AI191650 Hs 221436 ESTs 334
451735 AW407892 ESTs 381
446804 AW572304 Hs 271260 ESTs, Moderately similar to dJ63G53 [H 339
448515 H68441 Hs 13528 hypothetical protein FLJ14054 347
452816 AA131789 Hs 61509 ESTs 370
439484 AW970218 Hs 135254 Homo sapiens clone 1 thrombospondln mRNA 404
433688 AA628467 Hs 112572 Homo sapiens cDNA FLJ14130 fis, clone MA 403
424580 AA446539 Hs 339024 ESTs, Weakly simllarto A46010 X-llnked 344
447578 AA912347 Hs 136585 ESTs, Weakly slmilarto JC5314 CDC28/cdc 564
447896 AI436124 Hs 294069 Homo sapiens cDNA FLJ13384 fis, clone PL 572
417696 BE241624 Hs 82401 CD69 antigen (p60, early T-cell actlvati 490
443679 AK001810 Hs 9670 hypothetical protein FLJ10948 1031
414516 AI307802 ESTs, Weakly slmilarto T43458 hypothet 344
435916 AW001885 Hs 114103 ESTs 626
452664 AA398859 Hs 18397 hypothetical protein FLJ23221 422
427890 AA435761 ESTs 661
434666 AF151103 Hs 112259 T cell receptor gamma locus 369
450400 AI694722 Hs 279744 ESTs 333
406800 AA505535 gb nh84tι10 s1 NCI.CGAP.Br1 1 Homo sapien 485
429655 U48959 Hs 211582 myosln, light polypeptide kinase 332
425701 AA361850 Hs 240443 Human clone 137308 mRNA, partial eds 416
453767 AB011792 Hs 35094 extracellular matnx protein 2, female o 350
452336 AA960961 Hs 305953 zinc finger protein 83 (HPF1) 580
418117 AI922013 Hs 83496 linker for activation of T cells 391
407753 AL045916 Hs 293419 ESTs 404
428780 AI478578 Hs 153714 ESTs 353
429439 AL049268 Hs 202684 Homo sapiens mRNA, cDNA DKFZp564G103 (fr 385
412000 AW576555 Hs 15780 ATP binding cassette, sub family A (ABC1 347
448051 BE615453 Hs 346509 dedicator of cyto kinesis 1 356
406801 AW242054 Hs 190813 ribosomal protein L9 437
424698 AA164366 Hs 151973 hypothetical protein FLJ23511 484
442176 AA983764 Hs 128910 ESTs 417
416427 BE244050 Hs 79307 Rac/Cdc42 guanine exchange factor (GEF) 454
413156 AA127133 gb zl87e03 r1 Stratagene colon (937204) 365
424078 AB006625 Hs 139033 paternally expressed 3 400
417410 AF063020 Hs 82110 PC4 and SFRS1 Interacting protein 1 401
434958 T99949 Hs 303428 Homo sapiens cDNA FLJ14832 fis, clone OV 358
427544 AI767152 Hs 181400 ESTs, Weakly slmilarto I78885 serine/th 347
453510 AI699482 Hs 42151 ESTs 415
442287 AW952703 Hs 8182 synaptc nuclei expressed gene 1b 346
414142 AW368397 Hs 334485 hemlcentln (fibulin 6) 490
421512 AB007923 Hs 265848 myomegalin 341
437176 AW176909 Hs 42346 calcineuriπ binding protein calsarcln-1 531
426992 BE244961 Hs 343200 FE65 LIKE 2 474
431615 AW295859 Hs 235860 ESTs 376
458368 BE504731 Hs 138827 ESTs 377
406282 Homo sapiens mRNA full length Insert cDN 362
411546 BE172648 Hs 75415 beta-2-mlcroglobulin 435
421956 AA301180 gb EST14093 Tests tumor Homo sapiens cD 512
422964 AW439476 Hs 256895 ESTs 415
410544 AI446543 Hs 95511 ESTs 333
459508 R83265 Hs 205956 EST 339
409038 T97490 Hs 50002 small Inducible cytokine subfamily A (Cy 4 81
421823 N40850 Hs 28625 ESTs 696
407568 AA740964 Hs 62699 ESTs 332
430810 AI742514 Hs 158732 ESTs 334
423705 F11425 ribosomal protein S3 550
436553 AW407157 Hs 8997 Immunoglobulin lambda locus 497
403325 C2000428*gl|7705383|ref|NP_057536 1| GC 459
437255 R58970 Hs 9887 ESTs 358 439665 W93979 gb zd97h10 r1 Soares fetalheart_NbHH19W 354
450000 AI952797 Hs 10888 hypothetical protein FLJ21709 339
449787 AA005341 ESTs 369
429760 AW137682 Hs 134589 ESTs 339
442070 BE244622 Hs 8084 hypothetcal protein dJ465N242 1 371
415733 AI052628 Hs 271570 ESTs, Weakly similar to 2109260A B cell 335
424084 AI940675 Hs 20914 hypothetical protein FLJ23056 351
427732 NM.002980 Hs 2199 secretm receptor 366
431177 NM.003304 Hs 250687 transient receptor potential channel 1 367
447571 AF274863 Hs 18889 DKFZP434M183 protein 355
458018 AI199575 Hs 37716 ESTs 463
453880 AI803166 Hs 135121 ESTs, Weakly similar to I38022 hypothet 421
425456 T70445 Hs 157850 ribosomal protein L9 519
442587 AK001846 HS 8412 Homo sapiens cDNA FLJ10984 fis, clone PL 353
443998 AI620661 Hs 296276 ESTs 477
435289 AA677540 Hs 117064 ESTs 350
445837 AI261700 Hs 145544 ESTs 498
442561 NM 013450 HS 8383 bromodomain adjacent to zinc finger doma 660
433205 AB040901 Hs 23542 KIAA1468 protein 340
422241 Y00062 Hs 170121 protein tyrosine phosphatase, receptor t 332
437365 AW965771 Hs 91065 hypothetical protein DKFZp761B2423 394
419902 AA804409 Hs 118920 ESTs 347
445618 H79667 Hs 237642 Homo sapiens cDNA FLJ12052 fis, clone HE 386
433019 AI208513 Hs 279915 translocase of inner mltochondπal membr 4 10
425231 AA527161 ESTs 356
428046 AW812795 Hs 337534 ESTs, Moderately similar to I38022 hypot 599
409667 AW452447 Hs 283107 ESTs, Weakly slmilarto T22143 hypothet 332
414474 AA147968 Hs 31297 duodenal cytochrome b 365
422128 AW881145 gb QV0 OT0033-010400-182 a07 OT0033 Homo 635
447754 AW073310 Hs 163533 intron of HER4 347
422276 AL137690 Hs 114173 Homo sapiens mRNA, cDNA DKFZp434O032 (fr 348
451678 AA374181 Hs 26799 DKFZP564D0764 protein 451
451744 AI813757 F-box only protein 29 358
449609 BE246434 Hs 289026 guanine nucleotide binding protein (G pr 346
426276 AW881411 Hs 169078 hypothetical protein FLJ23018 351
440602 AI743491 Hs 292692 ESTs 344
433253 AW450502 Hs 24218 ESTs 337
406757 T65957 Hs 77039 ATP synthase, H transporting, mitochoπdr 373
417032 AA192469 Hs 271838 ESTs 356
438086 AA336519 Hs 83623 nuclear receptor subfamily 1, group I, m 330
436987 AA740990 Hs 120551 toll like receptor 10 431
407374 AA724738 Hs 131034 ESTs, Weakly simllarto I78885 seππe/th 5 21
412088 AI689496 Hs 108932 ESTs 412
447022 AW291223 Hs 157573 ESTs 448
450654 AJ245587 Hs 25275 Kruppel type zinc finger protein 351
450701 H39960 Hs 288467 hypothetical protein XP 098151 (leuclπe- 543
408491 AI088063 Hs 7882 ESTs 535
451323 AI903313 Hs 34579 ESTs, Moderately similar to ALU6.HUMAN A 330
407183 AA358015 gb EST66864 Fetal lung III Homo sapiens 350
436749 AA584890 Hs 5302 lectin, galactoslde-blnding, soluble, 4 922
439138 AI742605 Hs 193696 ESTs 333
450219 AI826999 Hs 224624 ESTs 332
456373 BE247706 Hs 89751 membrane spanning 4-domaIns, subfamily A 420
424677 U09414 zinc finger protein 137 (clone pHZ 30) 355
451240 AJ131693 Hs 58103 A kinase (PRKA) anchor protein (yotlao) 346
437205 AL110232 Hs 279243 Homo sapiens mRNA, cDNA DKFZp564D2071 (f 336
421893 NM 001078 Hs 109225 vascular cell adhesion molecule 1 393
429493 AL134708 Hs 145998 ESTs 398
449539 W80363 Hs 58446 ESTs 355
417339 AI912592 Hs7882 ESTs 4 62
448878 AW204582 Hs 224906 ESTs 335
425247 NM.O0594O Hs 155324 matrix metalloprotelnase 11 (stromelysln 562
418310 AA814100 Hs 86693 ESTs 386
403903 C5001632* gl|10645308|gb|AAG214301|AC00 423
437644 AA748575 Hs 136748 lectin like NK cell receptor 366
450788 AI738410 ESTs 394
453392 U23752 Hs 32964 SRY (sex determining region Y) box 11 487
407758 D50915 Hs 38365 KIAA0125 gene product 409
419556 U29615 Hs 91093 chltlπase 1 (chltotnosldase) 446
439854 T62993 Hs 347609 gb yb99a06 r1 Stratagene lung (937210) H 330
430770 AA765694 Hs 123296 ESTs 394
420224 M84371 Hs 96023 CD19 antigen 413
419255 AA235672 Hs 87491 ESTs 389
422583 AA410506 Hs 27973 KIAA0874 protein 369
445669 AI570830 Hs 174870 ESTs 364
447932 AA837474 Hs 20021 vesicle-associated membrane protein 1 (s 337
411982 H53601 gb yq87g05 s1 Soares fetal liver spleen 352
451583 AI653797 Hs 24133 ESTs 332
443184 AI638728 Hs 131973 ESTs 373
440650 R44692 Hs 326801 Human DNA sequence from PAC 75N13 on chr 406
418007 M13509 Hs 83169 matrix metalloprotelnase 1 (interstitial 685
452107 AB020681 Hs 27973 KIAA0874 protein 335
407811 AW190902 Hs 40098 cystelne knot superfamily 1 , BMP antagon 368
455002 AW850286 gb lL3 CT0219-161199031-H11 CT0219 Homo 353
408063 BE086548 Hs 42346 calclneurin binding protein calsardn-1 388
417689 AA828347 Hs 90998 KIAA0128 protein, septn 2 348 421361 AI246129 ESTs 3.63
458080 BE142728 gb:MRO-HT0157-021299-004-d08 HT0157 Homo 3.33
422867 L32137 Hs.1584 cartilage oϋgomeric matrix protein (pse 4.41
414085 AA114016 Hs.75746 aldehyde dehydrogenase 1 family, member 3.39
456034 AW450979 gb:UI-H-BI3-ala-a-12-0-Ul.s1 NCI_CGAP_Su 3.44
427585 D31152 Hs.17972! collagen, type X, alpha 1 (Schmld metaph 4.10
406964 M21305 FGENES predicted novel secreted protein 3.98
411089 AA456454 cell division cycle 2-like 1 (PITSLRE pr 3.64
TARI F 9R
Pkey: Unique Eos probeset identifier number
CAT number. Gene cluster number
Accession: Genbank accession numbers
Pkey CATnumber Accession
409385 1107581 T65940 T64515 AA071267 AA071334
422667 224778.1 AI758223 AW469334 BF940841 AW080348 AI270363 AI055892 BE464168 BF431797 BE350144 BF448739 AI693409 BF432999 D62848
AA398070 AI383375 AW611490
415386 112815 R95033 H15506 Z43087 F07410 H54108 H98000
455653 200977.1 BF820280 BE154075 BE154018 BE153509 BE153973 BE064861 BE065075 BE064684 BE153602 BE153852 BE153847 BE064772
BE064842 BE153557
406760 00 AA829363
421341 1407.1 NM.007329 AF159456 AJ243212 AJ297935 AA295769 NM 017579 AJ243224 AI492875 AI796676 AI749838 AA918144 AI814590
AI923531 BF513992 AI720725 AI150879 AI279072 AW612904 AI492104 AI284510 AI141231 AA613554 AW662148 AW769047 AA565985
AW612888 AU100513 BG955585 BG955588 AA295763 BE829414 BF760645 BG954398 AA295332 AA295795 BE932867 AW769569
T89953 BE934311
411962 23077101 AA099050 AA099526 T47733
451735 4800281 BG113814 AW407892 AI812096 AW076043
414516 60847.1 AK057782 AI146454 BG703115 AI765980 AI948611 AA889263 AA947457 BG547193 H11947 Z38147 F10426 BF447329 H11946 T74968
F06195 BG548563 AI004988 AA148735 AI307802 AI439791 BE041453 AI984904 AA148734 F12823
427890 13739881 AA417099 AA435761 AA972917 AI660387
406800 00 AA505535
413156 12243801 AW958912 AA384396 T72119 AA127133
421956 4611031 AV750327 AA300961 AA301180 AW963779
423705 290138 BG875506 AI299893 AA989327 BE708123 AI859076 AI434010 AA347691 F11425 AA329878
439665 244971 AF086498 AW955697 W93979 AI936062 AW268568 AA364461 W93980 BI914847 BI523483
449787 79759.1 AW975633 AW961632 AA322539 AW513289 AI864190 AW073506 AI016894 AA747635 AA730405 AA418033 AI609549 AI873981
AA005341 BE182658 AA004291
425231 2355041 AA527161 BG211784 AA527065 AA505489 AW512550
422128 17516 Ϊ6 BI261864 BI036453 BI023096 BI023388 AA331991 AV721898 AW881145 AA490718 M85637 T06067 AV761102 BI023091 Bi022906
451744 181594 BG165570 AI973190 BE221960 AI813757
424677 251837 U09414 NM.003438 AA503545 AI022449 AA043458 AA766074 AA765442 AA805052 AI028211 AW609708
450788 513262.1 AI971725 AI738410 AW016905
411982 1144977.1 AW880868 BE003925 H53601
455002 10890921 BE143505 BF374194 BF374190 AW850286
421361 2678431 AA287780 AI246129 AI708426 Z36873
458080 11642451 BI602455 AW937124 AA834047 BE142728
456034 6855861 AA136653 AA136656 AW450979 AA984358 AA809054 AW238038 AA492073 BE168945
411089 55976 BI009308 BI009893 BF922023 BF922909 BF922913 BF922096 BF957733 BE701791 AA456454 AA579876 BF933710 AA091294 BI007291
AW905577 AW975593 AA713730 AW836781 AA666384 AA551106 BF594606 AI082382 AI955808 AI679895 AI679386 BF435555
AA586369 AA551351 AA595822 AA565188 BF808855 AA584921 N86077 AA601031 AA633188 AA514764 AA454562 AA551297 AA936109
BI009389 AW897806 BE815442 BF739374 BI0O931O BF925422 BF933709 BF922034 BF925465 BI009680
TABLE 9C
Pkey: Unique number corresponding to an Eos probeset
Ref: Sequence source. The 7 digit numbers In this column are Genbank Identifier (GI) numbers. "Dunham I. et al." refers to the publication entted "The DNA sequence of human chromosome 22." Dunham I. et al., Nature (1999) 402:489-495. Strand: Indicates DNA strand from which exons were predicted. NLpositlon: Indicates nucleotide positions of predicted exons.
Pkey Ref Strand NLpositlon
404246 7406725 Plus 82477-82628,82721-82817,82910-83071,8314
406282 7549620 Plus 61692-61955
403325 8440025 Minus 109763-109926
403903 7710671 Minus 101165-102597 TABLE 10A About 289 oenes downregulated In lung metasiπς g in tha hraln relative to normal lunα
Pkey Unique Eos probeset Identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentile of normal lung Als divided by the 90th percentle of lung metastases to the brain Als, where the 15th percentle of all normal body tissue Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
417204 N81037 Hs 1074 surfactant, pulmonary-associated protein 5005 125
418026 BE379727 Hs 83213 fatty a d binding protein 4, adipocyte 31 39 27
424206 NM 003734 Hs 198241 amine oxldase, copper containing 3 (vase 2942 40 102
410677 NM 003278 Hs 65424 tetranectn (plasmiπogeπ binding protein 2489 1691
435684 NM 001290 Hs4980 LIM domain binding 2 1800 61 114
415162 AF035718 Hs 78061 transcπpton factor 21 15 10 2293
409385 AA071267 gb zm61g01 r1 Stratagene fibroblast (937 1440 14
407694 U77594 Hs 37682 rβfinolc acid receptor responder(tazaro 14 18 9 67
441835 AB036432 Hs 184 advanced glycosylation end product sped 14 15 64116
453655 AW960427 Hs 342874 transforming growth factor, beta recepto 1342 80
415274 AF001548 Hs 78344 myosiπ, heavy polypeptide 11, smooth mus 1295
412047 AA934589 Hs 49696 ESTs 11 68
423778 Y09267 Hs 132821 flavin containing monooxygenase 2 1061
407744 AB020629 Hs 38095 ATP-blπding cassette, sub family A (ABC1 1036
427019 AA001732 Hs 173233 hypothetical protein FLJ10970 980
429350 AI754634 Hs 131987 ESTs 951
410016 AA297977 Hs 57907 small Inducible cytokine subfamily A (Cy 949
453310 X70697 Hs 553 solute carrierfamlly 6 (πeurotransmltte 947
407245 X90568 Hs 172004 tltln 922
426752 X69490 Hs 172004 tltln 913
431723 AW058350 Hs 16762 Homo sapiens mRNA, cDNA DKFZp564B2062 (f 906
428043 T92248 Hs 2240 uteroglobin 896
435146 R44557 Hs 23748 ESTs 856
416950 AL049798 Hs 80552 demnatopontln 853
441281 BE501247 Hs 144084 ESTs 852
404246 Target Exon 839
432128 AA127221 Hs 296502 Interleukin 1 receptor like 1 835
430998 AF128847 Hs 204038 Indolethylamlne N-methyltransferase 820
417355 D13168 Hs 82002 eπdotielln receptor type B 818
422287 F16365 Hs 114346 cytochrome c oxidaεe subunlt Vila polype 816
438150 AA037534 Hs 342874 transforming growth factor, beta recepto 809
453676 AW853745 Hs 286035 hypothetcal protein FLJ22686 800
422550 BE297626 Hs 296049 mlcrofibrillar associated protein 4 773
422667 H25642 ESTs 750
423007 AA320134 Hs 196029 Homo sapiens mRNA for KIAA1657 protein, 736
454229 AW957744 Hs 278469 lacrlmal prollπe rich protein 715
436394 AA531187 Hs 126705 ESTs 710
453574 AI767947 Hs 50841 ESTs 707
420225 AW243046 Hs 282076 Homo sapiens mRNA for KIAA1650 protein, 688
443709 AI082692 Hs 134662 ESTs 679
424027 AW337575 Hs 201591 ESTs 678
428769 AW207175 Hs 106771 ESTs 669
414464 AI870175 Hs 13957 ESTs 667
453180 N46243 Hs 110373 ESTs, Highly similar to T42626 secreted 651
443062 N77999 Hs 8963 Homo sapiens mRNA full length insert cDN 648
459247 N46243 Hs 110373 ESTs, Highly similar to T42626 secreted 629
451154 AA015879 Hs 33536 ESTs 613
438873 AI302471 Hs 124292 Homo sapiens cDNA FLJ23123 fis, clone L 608
411939 AI365585 Hs 146246 ESTs 597
456898 NM 001928 Hs 155597 D component of complement (adlpsln) 597
418058 AW161552 Hs 83381 guanine nucleotide binding protein 11 590
410066 AL117664 Hs 58419 DKFZP586L2024 protein 564
439745 AL389981 Homo sapiens mRNA full length Insert cDN 560
401974 NM.018896* Homo sapiens calcium channel, 556
429640 U83508 Hs 2463 aπglopoletn 1 555
421218 NM 000499 Hs 72912 cytochrome P450, subfamily I (aromatc c 551
430310 U60115 Hs 239069 four and a half LIM domains 1 550
430468 NM 004673 Hs 241519 aπglopoletπ like 1 547
413948 C05145 Hs 75636 myosln light chain 2a 537
410023 AB017169 Hs 57929 slit (Drosophila) homolog 3 520
418935 T28499 Hs 89485 carbonic anhydrase IV 520
446017 N9823B Hs 55185 ESTs 515
420105 AW015571 Hs 32244 ESTs, Weakly simllarto FMOD.HUMAN FIBRO 511
420958 AA309431 Hs 66 Interleukin 1 receptor-like 1 510
409153 W03754 Hs 50813 hypothetical protein FLJ20022 507
410545 U32324 Hs 64310 Interleukin 11 receptor, alpha 507
412002 AA913024 Hs 84698 Homo sapiens cDNA FLJ14300 fis, clone PL 507
442832 AW206560 Hs 253569 ESTs 506
444561 NM 004469 Hs 11392 c fos Induced growth factor (vascular en 506
431848 AI378857 Hs 271605 ESTs, Highly similar to AF175283 1 zinc 497
425764 AW996009 Hs 112572 Homo sapiens cDNA FLJ14130 fis, clone MA 494
427605 NM.000997 Hs 337445 ribosomal protein L37 493 450008 H52970 Hs 36688 WAP four-dlsullide core domain 1 490
421177 AW070211 Hs 102415 Homo sapiens mRNA, cDNA DKFZp586N0121 (f 486
451607 AI439103 Hs 7945 AIE-75 binding protein protein 486
408741 M73720 Hs 646 carboxypeptdase A3 (mast cell) 485
418947 W52990 Hs 22860 ESTs 485
419111 AA234172 Hs 137418 ESTs 482
447371 AA334274 Hs 18368 DKFZP564B0769 protein 477
416030 H15261 Hs 21948 ESTs 477
423690 AA329648 Hs 23804 ESTs, Weakly slmilarto PN0099 son3 prot 474
439551 W72062 Hs 11112 ESTs 473
412810 M21574 Hs 74615 platelet derived growth factor receptor, 471
424310 AA338648 Hs 50334 testes development related NYD SP22 470
413474 T86312 Hs 334485 Homo sapiens cDNA FLJ14438 fis, clone HE 466
423099 NM 002837 Hs 123641 protein tyrosine phosphatase, receptor t 463
439335 AA742697 Hs 62492 NM 052863 Homo sapiens secretoglobln, fa 460
425498 AL096725 Hs 289010 DKFZP434B103 protein 459
445516 R50291 Hs 10846 ESTs, Weakly similar to JH0783 dlamlne N 458
420626 AF043722 Hs 99491 RAS guanyl releasing protein 2 (calcium 458
408374 AW025430 Hs 155591 forkhead boxFI 457
440647 BE397806 poly(A) binding protein, cytoplasmic 1 456
416986 AI471952 Hs 49776 ESTs 455
416585 X54162 Hs 79386 lelomodlπ 1, smooth muscle (LMOD1) (Thy 453
407891 AA486620 Hs 41135 endomuclπ-2 450
409064 AA062954 Hs 141883 ESTs 449
427164 AB037721 Hs 173871 KIAA1300 protein 439
426488 X03350 Hs4 alcohol dehydrogenase 1B (class I), beta 436
410036 R57171 Hs 57975 calsequestπn 2 (cardiac muscle) 432
447205 BE617015 Hs 11006 ESTs Moderately similar to T17372 plasm 429
418307 U70867 Hs 83974 solute carrierfamlly 21 (prostaglandln 427
441003 BE172240 Hs 126379 ESTs, Weakly slmila to 138022 hypothet 422
414290 AI568801 Hs 71721 ESTs 422
423387 AJ012074 vasoactive Intestinal peptide receptor 1 419
413956 AI821351 Hs 193133 ESTs, Weakly slmilarto ALU7.HUMAN ALU S 416
417967 BE244373 Hs 1119 nuclear receptor subfamily 4, group A m 415
424711 NM 005795 Hs 152175 caldtonln receptor like 412
427983 M17706 Hs 2233 colony stimulating factor 3 (granulocyte 412
456676 AI870001 Hs 334479 ESTs Moderately similar to KIAA1139 pro 410
451245 AA016218 Hs 58231 ESTs 10
424433 H04607 Hs 78061 ESTs 409
452541 AA022569 Hs 29802 silt (Drosophila) homolog 2 409
424137 AA335769 Hs 16262 ESTs 409
423334 AKO0O906 Hs 127273 hypothetical protein FLJ10044 408
422640 M37984 Hs 118845 troponin C, slow 406
418807 NM 004944 Hs 88646 deoxynbonuclease I like 3 404
406923 S70622 gb G1 phase specific gene (3 region) [h 404
420556 AA278300 Hs 124292 Homo sapiens cDNA FLJ23123 fis, clone L 403
424054 AA334511 Hs 26638 membrane spanning 4-domalns, subfamily A 402
441499 AW298235 Hs 101689 ESTs 402
420256 U84722 Hs 76206 cadherin 5, type 2, VE-cadherin (vascula 402
427383 NM 005411 Hs 177582 surfactant pulmonary associated protein 401
433855 AA834082 Hs 307559 ESTs 399
403421 NM.016369* Homo sapiens claudln 18 (CLDN 398
401929 C17001690 gl|6005701|ref|NP_009099 1|AT 398
443577 AI078033 Hs 177170 ESTs, Weakly simllarto ALU8.HUMAN ALU S 398
445624 AW140103 Hs 78880 HvB (bacterial acetolactate synthase) I 397
408614 AL137698 Hs 46531 Homo sapiens mRNA, cDNA DKFZp434C1915 (f 396
420174 AI824144 Hs 199749 ESTs 396
434975 AA657884 Hs 314413 ESTs 395
418728 AW970937 Hs 293843 ESTs 395
432231 AA339977 Hs 274127 CLST 11240 protein 394
432894 AW167668 Hs 279772 brain specific protein 394
435424 AW083883 Hs 37896 Homo sapiens cDNA FLJ 13510 fis, clone PL 393
427007 NM.006283 Hs 173159 transforming, acidic coiled-coll contain 391
430803 AW951830 Hs 283402 TC eta 391
446998 N99013 Hs 16762 Homo sapiens mRNA, cDNA DKFZp564B2062 (f 390
419150 T29618 Hs 89640 TEK tyrosine kinase, endothelial (venous 390
432740 AF061034 Hs 278898 tumor necrosis factor alpha inducible ce 389
432519 AI221311 Hs 130704 ESTs, Weakly slmilarto BCHUIA S-100 pro 387
454072 AW572954 Hs 252851 ESTs 387
449261 AI637592 ESTs 386
422195 AB007903 Hs 113082 KIAA0443 gene product 386
411988 AA455459 Hs 164480 ESTs, Weakly slmilarto T50609 hypothet 384
453467 AI535997 Hs 30089 ESTs 383
409882 AJ243191 Hs 56874 heat shock 27kD protein family, member 7 382
414577 AI056548 Hs 72116 hypothetical protein FLJ20992 similar to 381
427418 AA402587 LAT1-3TM protein 379
441723 R72137 Hs 7949 DKFZP586B2420 protein 377
433614 W07475 Hs 277101 cytochrome c oxldase subunlt IV Isoform 376
420043 U08198 Hs 1285 complement component 8, gamma polypept 374
425887 AL049443 Hs 161283 Homo sapiens mRNA, cDNA DKFZp586N2020 (f 374
442262 BE170651 HS 8700 deleted In liver cancer 1 373
447081 Y13896 Hs 17287 potassium Inwardly rectifying channel, s 372
453355 AW295374 Hs 31412 myopodln 372
417033 H83784 KIAA0717 protein 372
458504 AW070634 Hs 144794 ESTs 372
450954 AI904740 Hs 25691 receptor (caldtonln) activity modifying 369 458816 BE314567 Hs.211440 ESTs 3.68
401234 mltogen-a ivated protein kinase 8 Inter 3.66
456594 U90545 Hs.327179 solute carrierfamlly 17 (sodium phospha 3.65
435823 R07856 Hs.16355 ESTs 3.63
415775 H00747 Hs.29792 ESTs, Weakly similar to I38022 hypothet 3.63
415386 Z43087 gb:HSC13A121 normalized infant brain cDN 3.62
415780 U75898 Hs.78846 heat shock 27kD protein 2 3.61
448274 AI268097 Hs.67317 Homo sapiens cDNA FLJ11775 fis, clone HE 3.61
434951 AF161442 Hs.191591 Homo sapiens HSPC324 mRNA, partial eds 3.60
425622 AW360847 Hs.16578 ESTs 3.60
432985 T92363 Hs.178703 ESTs 3.60
447265 W23666 gb:zb46g08.r1 Soares_fetaUuπg_NbHL19W 3.59
418965 AI002238 Hs.11482 splicing factor, arginlne/seriπe-rich 11 3.58
450696 AI654223 Hs.16026 hypothetical protein FLJ23191 3.58
414593 BE386764 gb:601273249F1 NIH.MGC.20 Homo sapiens c 3.58
447742 AF113925 Hs.19405 caspase recruitment domain 4 3.57
426828 NM 000020 Hs.172670 activln A receptor type ll-llke 1 3.56
451220 AF124251 Hs.26054 novel SH2-coπtaiπlπg protein 3 3.56
441503 AW172263 Hs.185202 ESTs 3.54
447540 AL135716 Hs.263780 ESTs 3.53
416157 NM 003243 Hs.342874 transforming growth factor, beta recepto 3.53
420983 W95228 Hs.100764 cathepsln G 3.53
413802 AW964490 Hs.32241 ESTs, Weakly simllarto S65657 alpha-1C- 3.53
431971 BE274907 Hs.77385 myosln, light polypeptide 6, alkali, s o 3.53
411085 AF022991 Hs.68398 period (Drosophila) homolog 1 3.52
455653 BE154075 gb:PM0-HT0339-200400-010-E05 HT0339 Homo 3.52
403287 Target Exon 3.52
406760 AA829363 gb:of08g04.s1 NCI_CGAP_Co12 Homo sapiens 3.50
425009 X58288 Hs.154151 protein tyrosine phosphatase, receptor t 3.49
442321 AF207664 Hs.8230 a dislntegrin-llke and metalloprotease ( 3.49
418381 AA682393 Hs.119237 ESTs 3.48
455698 BE068097 gb:CM1-BT0368-061299-060-c08 BT0368 Homo 3.47
419360 AI148037 gb:qg61e01.r1 Soares.testls.NHT Homo sap 3.46
456589 W79583 Hs.104258 Homo sapiens mRNA, exon 1, 2, 3, 4, on 3.44
443932 AW888222 Hs.9973 tensln 3.43
421341 AJ243212 deleted In malignant brain tumors 1 3.43
442743 AI801351 Hs.302110 ESTs, Weakly slmilarto MUC2.HUMAN MUCIN 3.43
411020 NM 006770 Hs.67726 macrophage receptor with collagenous sir 3.43
432485 N90866 Hs.276770 CDW52 antigen (CAMPATH-1 antigen) 3.43
411962 AA099050 gb:zk85d12.r1 Soares_pregπanLuterus NbH 3.42
443873 AL048542 Hs.16291 ESTs 3.42
453874 AW591783 Hs.36131 collagen, type XIV, alpha 1 (undulln) 3.41
454741 BE154396 gb:CM2-HT0342-091299-050-b05 HT0342 Homo 3.41
403211 NM 005400*:Homo sapiens protein kinase C 3.39
445107 AI208121 Hs.147313 ESTs, Weakly simllarto I38022 hypothet 3.39
444769 AI191650 Hs.221436 ESTs 3.38
448323 AI492298 Hs.170915 ESTs 3.37
457567 AW939074 gb:QV1-DT0069-010200-057-c12 DT0069 Homo 3.36
424423 N56160 Hs.32916 nascent-polypeptde-assoclated complex a 3.35
451735 AW407892 ESTs 3.35
421326 AF051428 Hs.103504 estrogen receptor 2 (ER beta) 3.33
446804 AW572304 Hs.271260 ESTs, Moderately similar to dJ63G5.3 [H. 3.32
41435B AA476456 Hs.142614 ESTs 3.32
430212 AA469153 gb:nc67f04.s1 NCI.CGAP.Prl Homo sapiens 3.31
436061 AI2485B4 Hs.190745 Homo sapiens cDNA: FLJ21326 fis, clone C 3.31
414424 BE296309 Hs.125902 ublquitin specific protease 2 3.31
440288 D81015 Hs.125382 ESTs 3.31
414121 AA151719 Hs.95834 ESTs 3.30
410118 AW590680 von Willebrand factor 3.28
433633 AI880516 Hs.84630 ESTs, Weakly similar to 2004399A chromos 3.28
417302 BE245812 Hs.8941 ESTs 3.28
417451 AW007280 Hs.115537 putative dlpept ase 3.27
448515 H68441 Hs.13528 hypothetical protein FLJ14054 3.27
423196 AK001866 Hs.125139 hypothetical protein FLJ 11004 3.26
404179 Target Exon 3.26
413591 AA130636 Hs.188677 ESTs 3.26
447560 AF065214 Hs.18858 phospholipase A2, group IVC (cytosolic, 3.24
417075 R54506 Hs.118795 hypothetical protein FLJ10008 3.24
456855 AF035528 Hs.153863 MAD (mothers against decapentapleglc, Dr 3.23
421952 AA300900 Hs.98849 dyneln light chain 2B (DNLC2B) 3.22
434190 AA627122 Hs.147644 ESTs 3.21
452816 AA131789 Hs.61509 ESTs 3.21
406702 Z20656 myosln, heavy polypeptide 6, cardiac mus 3.21
415126 D60945 gb:HUM141D04B Clontech human fetal brain 3.21
439484 AW970218 Hs.135254 Homo sapiens clone 1 thrombospondln mRNA 3.21
429283 R13008 Hs.276748 ESTs 3.21
433688 AA628467 Hs.112572 Homo sapiens cDNA FLJ14130 fis, clone MA 3.21
437275 AW976035 Hs.292396 ESTs, Weakly similar to A475B2 B-cell gr 3.20
429580 AA346839 Hs.209100 DKFZP434C171 protein 3.19
424580 AA446539 Hs.339024 ESTs, Weakly simllarto A46O10 X-llπked 3.19
426309 AI912555 Hs.157195 peptide YY, 2 (semlnalplasmlπ) 3.19
438411 H91928 Hs.169370 gb:ys81c10.r1 Soares retna N2b4HRHomo 3.18
406329 Target Exon 3.18
422686 BE180557 Hs.22588 ESTs 3.17
447578 AA912347 Hs.136585 ESTs, Weakly slmilarto JC5314 CDC28/cdc 3.17
456703 W07492 Hs.157101 ESTs 3.16 418021 M15881 Hs 1137 uromodulln (uromucold, Tamm Horsfall gly 316
447896 AI436124 Hs 294069 Homo sapiens cDNA FLJ 13384 fis, clone PL 316
453989 M63962 Hs 36992 ATPase, H? exchanging, alpha polypeptide 3 16
423488 AW748714 Hs 194720 gb QV3-BT0294-241199-025 c01 BT0294 Homo 316
417696 BE241624 Hs 82401 CD69 antigen (p60, early T cell actlvat 316
420937 AW966719 Hs 1340 colipase, pancreatic 315
443679 AK001810 Hs 9670 hypothetical protein FLJ10948 315
414325 AA251929 ESTs, Weakly similar to unnamed protein 3 15
459073 AW968616 Hs 296234 ESTs, Weakly slmilarto T31613 hypothet 315
428540 AA430001 Hs 279755 ESTs 314
433735 AA608955 Hs 109653 ESTs 314
424455 AA452006 Hs 333199 calcium channel, voltage-dependent, gamm 314
440636 AA897395 Hs 202248 ESTs, Weakly similar to T12525 hypothet 3 12
450119 AI683447 Hs 264371 ESTs, Weakly simllarto M3K3 HUMAN MITOG 312
414516 AI307802 ESTs, Weakly slmilarto T43458 hypothet 311
422126 AW973784 Hs 112028 MIsshapeπ/NIK-related kinase 310
450240 AA236063 Hs 62954 ferntn, heavy polypeptide 1 309
435916 AW001885 Hs 114103 ESTs 308
403875 Target Exon 308
440098 AA864798 Hs 186180 Homo sapiens cDNA FLJ23038 fis, clone L 308
412442 AI983730 Hs 26530 serum depnvation response (phosphatdyl 307
428434 AW363590 Hs 65551 Homo sapiens, Slmilarto DNA segment, Ch 306
452547 AA335295 Hs 74120 adipose specific 2 305
457661 AA917801 Hs 125910 ESTs 305
407102 AA007629 glycerol-3-phosphate dehydrogenase 1 (so 305
438137 AA778759 Hs 271690 ESTs 305
444325 AW152618 Hs 16757 ESTs 305
458871 AI990292 Hs 225457 ESTs 304
426411 AK000708 Hs 169764 hypothetical protein FLJ20701 304
448782 AL050295 G protein coupled receptor 116 (GPR116) 304
428224 X54017 Hs 183088 acrosin 304
450749 AI733114 Hs 130169 ESTs 303
407139 W81598 gbzd88g02 s1 Soares fetal heart_NbHH19W 303
446932 AA961459 Hs 125644 ESTs 303
422221 AA306649 Hs 169370 FYN oncogene related to SRC, FGR YES 302
421275 AW029312 Hs 99693 ESTs 302
412351 AL135960 Hs 73828 T-cell acute lymphocyte leukemia 1 301
451556 AW242829 Hs 144094 ESTs, Weakly similar to 138600 zinc ting 301
452664 AA398859 Hs 18397 hypothetical protein FLJ23221 301
452877 AI250789 Hs 32478 ESTs 300
427890 AA435761 ESTs 300
434666 AF151103 Hs 112259 T cell receptor gamma locus 300
450400 A1694722 Hs 279744 ESTs 300
428287 AF045239 Hs 321576 πng finger protein 22 300
425023 AW956889 Hs 154210 EDG-1 (endothelial differentiation, sph 300
TARI F 10R
Pkey Unique Eos probeset Identfier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT number Accession
409385 1107581 T65940 T64515 AA071267 AA071334 422667 224778.1 A1758223 AW469334 BF940841 AW080348 AI270363 AI055892 BE464168 BF431797 BE350144 BF448739 AI693409 BF432999 D62848
AA398070 AI383375 AW611490
439745 7961.1 AL389981 BM023607 BF475999 AI247103 AA838550 AA662305 AA838548 440647 12847.7 BE397806 BG823998 AI573099 AV725593 AA864452 AA883096 BG059834 AV661708 BE561462 BF804447 423387 2612.2 L13288 AA928785 AI608912 AW872978 AA565655 AI022915 AI304920 AI564366 AI668793 AI094557 T60038 R72302 H45409 AA508805
R46356 AA418798 BM129553 BM129126 BM129292 BM128865 AI808418 AI689932 AI806573 BF431808 AW872985 AW166269 H73241
T16182 AI264547 R73391 R72085 R72840 T83751 X75299 BF754348 R94105 AW449839 R73300 NM 004624 AI797007 BE045543
BF110021 BF754250 T83923 AW884084 AA903896 AA418962 L20295 R72351 H45098 AA961010 R73210 R46451 AW884085 BI022902
BI763932BI910138
449261 3029652.1 AI923721 AI860294 AI637592 427418 MH166094 AI633280 AW002589 AI760178 AI911270 AI277654 AI184927 AA402587 AA402398 AA455831 417033 37085.1 BC020779 AI857902 AI816715 AI936064 BE044451 AA688029 AW975331 AA192427 AA661735 F24489 AI382922 AI659751 F26660
F19507 F31628 AY037148 BF852989 BF852995 BF853000 BF853928 BF853920 BF846065 BF846063 BF848191 BF848190 BF853537
AA194737 BI010755 H83784 BG203405 BF853580 BF848198 BG545668 BF846059 BI010793 BI010796 AI218954 F28028 BF854481
BF846558 AA903899 AA854779 F33888 H83927 F25113 F36903 BG214764 AI863957 F26013 F26233 F20527 W37255 W32197 AA192426
AA902491 W33189 W32232 BG483879 BF846130 AA661823
415386 11281.5 R95033 H15506 Z43087 F07410 H54108 H98000 447265 1227845.1 AW962578 AI370391 23666 414593 58970.4 BE386764 AL603555 455653 200977.1 BF820280 BE154075 BE154018 BE153509 BE153973 BE064861 BE065075 BE064684 BE153602 BE153852 BE153847 BE064772
BE064842 BE153557
406760 0 0 AA829363 455698 1492345.1 BE068097 BE068148 BE068162 BE068145 BE068200 BE068158 BE068202 BE068086 BE068193 BE068091 419360 250410.1 AA236756 AA287178 AI148037 421341 1407.1 NM.007329 AF159456 AJ243212 AJ297935 AA295769 NM.017579 AJ243224 AI492875 AI796676 AI749838 AA918144 AI814590
AI923531 BF513992 AI720725 AH 50879 A1279072 AW612904 A1492104 AI284510 AI141231 AA613554 A 662148 AW769047 AA565985
AW612888 AU100513 BG955585 BG955588 AA295763 BE829414 BF760645 BG954398 AA295332 AA295795 BE932867 AW769569
T89953 BE934311 411962 2307710.1 AA099050 AA099526 T47733
454741 2203691 BE154396 BF846839 AW842318 AW817959 BE154393 BI050168
457567 10286091 AW970057 AW939073 AW940012 AW939074 AW939938 AW939206 AW939076 AA574383 BE160476 AA573577 AW750479
451735 4800281 BG113814 AW407892 AI812096 AW076043
430212 1404178.1 AI718503 AA469225 AA469153
410118 MH1429162 AU140255 AW590680 BI051042 R91271 H68390
406702 00 NA
415126 1857706.1 D61346 D60945 D80539 D81568
414325 16029.1 AK055560 AI223830 AW371603 AA564436 AA251799 AA143235 AA975269 AI565174 AI927242 AI052812 AA405571 AW103340 AI289757
AI472362 N26127 AI167485 AA826503 AI051406 AI431964 BG434126 AA282258 AA808282 BI766582 BE064109 BE064103 BE064088
BE064086 BE064115 BE064066 AA282732
414516 60847.1 AK057782 AI146454 BG703115 AI765980 AI948611 AA889263 AA947457 BG547193 H11947 Z38147 F10426 BF447329 H11946 T74968
F06195 BG548563 AI004988 AA148735 AI307802 AI439791 BE041453 A1984904 AA148734 F12823
407102 7177.2 AW945170 BF930905 F33652 BG057818 AI368018 AI421485 AI300352 AI378525 AI264177 AI276281 AI245302 AI281050 AI190036
AW451438 AW242903 AA910870 F22289 F19647 F22375 AW473816 BF445785 AA774528 F33447 C01077 AW772227 F17759 H42812
R09701 AA349096 R48772 H42892 H42537 R47898 N28263 H25721 F32386 H43971 R48205 F21390 H45809 AA007629 R47897 R83734
H45844 AW983653 H43970 H42536 H24495 R48875 H42961 H22079 R86018
448782 34980. AB018301 AL050295 BF513128 AW385080 AL551708 AI352542 AI829703 AI819388 AW629019 AW073189 AW273857 AW118768
AI453845 AI452494 AA886341 AI057144 AA904647 AI423547 AW263913 AI094774 AI434419 AI039546 A1002491 AI240412 Z25099
AA995178 AW050649 AW026140 AI796309 AI584012 BE166666 AI767991 AI309041 AA724059 AI695284 AI245095 T63971 Z40627
BE166681 BG570071 BF921915 BI562702 BG506502 AV658066 R48378 AA121543 AI096938 AA618131 H40993 R48277 AI352281
BG540263 BG538901 N95226 AI356752 AI221152 Z28777 R16574 AW966449 AA044116 AW797518 BI010405 AA044288 AI093508
BE140169 T64039 BG433106 AW130367 AW130361 N73937 AA127680 AW044037 AI096437 AA384077 BF941499 T93764 BG003285
427890 1373988.1 AA417099 AA435761 AA972917 AI660387 TABLE 10C
Pkey Unique number corresponding to an Eos probeset
Sequence source The 7 digit numbers In this column are Genbank Identifier (GI) numbers Dunham I et al " refers to the publication entted "The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489495
Strand Indicates DNA strand from which exons were predicted NLpositlon Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLpositlon
404246 7406725 Plus 82477-82628,82721-82817,82910-83071,8314
401974 3126777 Plus 85330-85683
403421 9665041 Minus 126609-126773,139986-140205
401929 3810670 Minus 3167-3286,4216-4310
401234 9929642 Plus 120173-120337
403287 8080320 Minus 126097-126411
403211 7630841 Minus 159211-159369
404179 4902741 Plus 34276-34463
406329 6982072 Minus 607903608271
403875 7709294 Plus 28026-28223
TABLE 11 A About 1198 genes unregulated In breast and lunα metastases to the brain relative to normal body tissues .
Pkey Unique Eos probeset identfier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentile of breast and lung metastases to the brain Als divided by the 90th percentile of normal body tissue Als, where the 15th percentile of all normal body tissue Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID πumber(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
408591 AF015224 Hs 46452 mammaglobin 1 4640 11 88
457200 U33749 Hs 197764 thyroid transcπpton factor 1 2240 84 124
414517 M24461 Hs 76305 surfactant, pulmonary-associated protein 2052 21 92
429170 NM 001394 Hs 2359 dual specificity phosphatase 4 1950 53108
419078 M93119 Hs 89584 insullnoma associated 1 1940 2996
452838 U65011 Hs 30743 preferentially expressed antgen In mela 1585 79121
409103 AF251237 Hs 112208 XAGE-1 protein 1568 1389
426283 NM 003937 Hs 169139 kynurenlnase (L-kynurenlne hydrolase) 1520 46104
425057 AA826434 Hs 1619 achaete scute complex (Drosophila) homol 1485 43
432441 AW292425 Hs 163484 intron of hepatocyte nuclear factor-3 al 1440 59
418738 AW388633 Hs 6682 solute earner family 7, (cationic amino 1385
407276 A1951118 Hs 326736 Homo sapiens breast cancer antgen NY-BR 1380
443171 BE281128 Hs 9030 TONDU 1305
427344 NM 000869 Hs 2142 5 hydroxytryptamine (serotonin) receptor 1225
431164 AA493650 Hs 94367 thyroid transcπpton factor 1 11 50
432415 T16971 Hs 289014 ESTs, Weakly similar to A43932 mucin 2 p 1085
457465 AW301344 Hs 122908 DNA replication factor 1025
422656 AI870435 Hs 1569 LIM homeobox protein 2 1015
410102 AW248508 Hs 279727 ESTs, homologue of PEM-3 [Ciona savlgnyi 1000
409269 AA576953 Hs 22972 steroid 5 alpha reductase 2-IIke, H5AR g 1000
429441 AJ224172 Hs 204096 lipophilin B (uteroglobin family member) 962
453884 AA355925 Hs 36232 KIAA0186 gene product 930
409041 AB033025 Hs 50081 Hypothetical protein, XP.051860 (KIAA119 915
429228 Al 553633 hypothetical protein MGC33630 877
451807 W52854 hypothetical protein FLJ23293 similar to 875
417576 AA339449 Hs 82285 phosphoπbosylglycinamideformyltransfer 8 55
444342 NM 014398 Hs 10887 similar to lysosome associated membrane 820
447342 AI199268 Hs 19322 Homo sapiens, Simllarto RIKEN cDNA 2010 810
443715 AI583187 Hs 9700 cyclin E1 805
447033 AI357412 Hs 157601 Predicted gene Eos cloned, secreted wΛ 805
444783 AK001468 Hs 62180 anlllln (Drosophila Scraps homolog), act 775
425211 M18667 Hs 1867 progastncsin (pepslnogen C) 7 67
445413 AA151342 Hs 12677 CGI-147 protein 765
439926 AW014875 Hs 137007 ESTs 736
405770 NM.002362 Homo sapiens melanoma antigen, 734
413585 AI133452 Hs 75431 flbrlnogen, gamma polypeptide 715
404561 tnchorhiπophalangeal syndrome I gene (T 715
439979 AW600291 Hs 6823 hypothetical protein FLJ10430 7 12
425843 BE313280 Hs 159627 death associated protein 3 7 11
450705 U90304 Hs 25351 Iroquois homeobox protein 2A (IRX-2A) ( 710
444670 H58373 Hs 332938 hypothetical protein MGC5370 710
418164 AI761820 Hs 41074 ESTs, Weakly slmilarto I39294 McLeod sy 705
421798 N74880 N acylsphingosine amldohydrolase (a d c 703
448275 BE514434 Hs 20830 kiπeslπ-like 2 695
428342 AI739168 Homo sapiens cDNA FLJ 13458 fis, clone PL 690
409557 BE182896 Hs 3686 ESTs 685
400292 AA250737 Hs 72472 BMP R1B (bone morphogenetc protein rec 675
425234 AW152225 Hs 165909 ESTs, Weakly slmilarto I38022 hypothet 672
428771 AB028992 Hs 193143 KIAA1069 protein 665
400205 NM 006265* Homo sapiens RAD21 (S pombe) 665
416208 AW291168 Hs 41295 ESTs, Weakly simllarto MUC2.HUMAN MUCIN 665
457211 AW972565 Hs 32399 ESTs, Weakly similar to S51797 vasodilat 6 63
409420 Z15008 Hs 54451 lamlnln, gamma 2 (nlceln (100kD), kalinl 660
448664 AI879317 Hs 334691 splicing factor 3a, subunltl, 120kD 655
430300 U60805 Hs 238648 oncostatn M receptor 640
408771 AW732573 Hs 47584 potassium voltage-gated channel, delayed 635
401451 NM.004496* Homo sapiens hepatocyte nude 633
433029 NM 014322 Hs 279926 opsln 3 (encephalopsln) 6 28
430044 AA464510 Hs 152812 ESTs 625
452259 AA317439 Hs 28707 signal sequence receptor, gamma (translo 620
426471 M22440 Hs 170009 transforming growth factor, alpha 615
428004 AA449563 Hs 151393 glutamate cystelne llgase, catalytc sub 615
427528 AU077143 Hs 179565 mlnlchromosome maintenance deficient (S 611
416294 D86980 Hs 79170 KIAA0227 protein 610
439963 AW247529 Hs 6793 platelet-activating factor acetylhydrola 606
401519 C15000476*gl|12737279lref|XP_012163 1| 605
420281 AI623693 Hs 323494 Predicted cation efflux pump 605
408908 BE296227 Hs 250822 serlne/threonlne kinase 15 605
436217 T53925 Hs 107 fibrinogen like 1 601
415138 C18356 Hs 295944 tissue factor pathway Inhibitor 2 600
408045 AW138959 Hs 245123 ESTs 595
433675 AW977653 Hs 75319 rlbonucleotde reductase M2 polypeptide 595 408298 AI745325 Hs 271923 Homo sapiens cDNA FLJ22785 fis clone K 595
431548 AI834273 Hs 9711 novel protein 585
407999 AI126271 Hs 49433 ESTs Weakly similar to YZ28.HUMAN HYPOT 583
407378 AA299264 Hs 57776 ESTs, Moderately similar to I38022 hypot 565
445903 AI347487 Hs 132781 class I cytokine receptor 565
401866 Target Exon 565
458814 AI498957 Hs 170861 ESTs, Weakly slmilarto Z195.HUMAN ZINC 561
440351 AF030933 HS 7179 RAD1 (S pombe) homolog 560
452461 N78223 Hs 108106 transcπpton factor 560
424140 Z48051 Hs 141308 myelin oligodendrocyte glycoprotein 560
400291 AA401369 downstream of breast cancer antgen NY B 555
429597 NM 003816 Hs 2442 a dislntegrin and metalloprotelnase doma 551
439580 AF086401 Hs 293847 ESTs, Moderately similar to S65657 alpha 545
439772 AL365406 Hs 10268 Homo sapiens mRNA full length insert cDN 545
443695 AW204099 ESTs, Weakly similar to AF1267801 retin 545
437834 AA769294 gb nz36g03 s1 NCI CGAP GCB1 Homo sapiens 535
430287 AW182459 Hs 125759 ESTs, Weakly slmilarto LEU5.HUMAN LEUKE 530
433485 AI493076 Hs 306098 aldo keto reductase family 1, member C2 530
423739 AA398155 Hs 97600 ESTs 530
438915 AA280174 Hs 285681 Williams Beuren syndrome chromosome regl 5 25
419875 AA853410 Hs 93557 proenkephalin 5 24
424834 AK001432 Hs 153408 Homo sapiens cDNA FLJ10570 fis, clone NT 523
437915 AI637993 Hs 202312 Homo sapiens clone N11 NTera2D1 teratoca 520
419743 AW408762 Hs 5957 Homo sapiens clone 24416 mRNA sequence 515
427944 AA417878 Hs 48401 ESTs Moderately similar to ALU8.HUMAN A 515
433023 AW864793 thrombospondln 1 515
420234 AW404908 Hs 96038 Rlc (Drosophila) like, expressed In many 5 14
427365 AI873274 downstream of breast cancer antgen NY B 514
416933 BE561850 Hs 80506 small nuclear πbonucleoprotein polypept 513
421502 AF111856 Hs 105039 solute earner family 34 (sodium phospha 512
410340 AW182833 Hs 112188 hypothetical protein FLJ13149 510
441031 AI110684 Hs 7645 fibrlnogen, B beta polypeptide 510
412140 AA219691 Hs 73625 RAB6 Interacting, kinesin like (rabklnes 508
422486 BE514492 Hs 117487 gene near HD on 4p163 with homology to 505
424905 NM 002497 Hs 153704 NIMA (neverin mitosis gene a) related k 505
433409 AI278802 Hs 25661 ESTs 502
422756 AA441787 Hs 119689 glycoprotein hormones, alpha polypeptide 500
424179 F30712 Hs 334573 Homo sapiens, clone IMAGE 4285740, mRNA 500
426318 AA375125 Hs 147112 Homo sapiens cDNA FLJ22322 fis, clone H 500
432378 AI493046 Hs 146133 ESTs 495
416111 AA033813 HS 79018 chromatn assembly factor 1 , subunlt A ( 495
441377 BE218239 Hs 202656 ESTs 495
426827 AW067805 Hs 172665 methylenetetrahydrofolate dehydrogenase 494
432886 BE159028 Hs 279704 chromatn accessibility complex 1 493
433862 D86960 Hs 3610 KIAA0205 gene product 493
423242 AL039402 Hs 125783 DEME 6 protein 491
413450 Z99716 Hs 75372 N acetylgalactosammidasθ alpha 490
403485 C3001813*gl|12737279|ref|XP_0121631| k 490
416000 R82342 Hs 79856 ESTs Weakly similar to S65657 alpha 1C 490
410555 U92649 Hs 64311 a dismtegπn and metalloprotelnase doma 486
415786 AW419196 Hs 257924 hypothetical protein FLJ13782 485
450149 AW969781 Hs 132863 Zlc family member 2 (odd paired Drosophi 485
424800 AL035588 Hs 153203 MyoD family Inhibitor 481
423554 M90516 Hs 1674 glutamine fructose-6 phosphate transamln 480
415989 AI267700 ESTs 480
424602 AK002055 Hs 151046 hypothetical protein FLJ11193 480
442760 BE075297 Hs 6614 ESTs Weakly slmilarto A43932 mucln 2 p 480
458098 BE550224 metallothlonein 1E (functional) 480
422880 AF228704 Hs 193974 glutathlone reductase 475
414343 AL036166 Hs 75914 coated vesicle membrane protein 475
441285 NM.002374 Hs 167 mlcrotubule associated protein 2 475
401464 hlstone deacetylase 5 470
412537 AL031778 nuclear tranεcnption factor Y, alpha 470
423453 AW450737 Hs 128791 CGI 09 protein 470
437387 A1198874 Hs 28847 AD026 protein 466
452526 W38537 Hs 280740 hypothetical protein MGC3040 465
424085 NM 002914 Hs 139226 replication factor C (activator 1) 2 (40 465
413753 U17760 Hs 75517 lamlnin, beta 3 (nlceln (125kD), kallnln 465
407137 T97307 gb ye53h05 s1 Soares fetal liver spleen 462
444858 AI199738 Hs 208275 ESTs, Weakly slmilarto ALUA.HUMAN llll 460
413597 AW302885 Hs 117183 ESTs 460
448105 AW591433 Hs 298241 Transmembrane protease, seπne 3 459
446872 X97058 Hs 16362 pyrimidinergic receptor P2Y, G protein c 452
407756 AA116021 Hs 38260 ublqultin specific protease 18 451
432731 R31178 Hs 287820 fibronectin 1 447
421227 R78581 Hs 266308 mosaic serine protease 445
418661 NM 001949 Hs 1189 E2F transcriptoπ factor 3 445
438378 AW970529 Hs 86434 hypothetical protein FLJ21816 445
447519 U46258 Hs 339665 ESTs 444
423673 BE003054 Hs 1695 matnx metalloprotelnase 12 (macrophage 440
404996 Target Exon 440
441790 AW294909 Hs 132208 ESTs 440
412970 AB026436 Hs 177534 dual specificity phosphatase 10 440
456508 AA502764 Hs 123469 ESTs, Weakly slmilarto AF2088551 BM-01 437
451752 AB032997 KIAA1171 protein 437
449722 BE280074 Hs 23960 cyclin B1 4 36 414706 AW340125 Hs 76989 KIAA0097 gene product 436
427712 AI368024 Hs 283696 ESTs 436
421305 BE397354 Hs 324830 dlptheria toxin resistance protein requl 433
429922 Z97630 Hs 226117 H1 hlstone family, member 0 433
444172 BE147740 ESTs, Moderately similar to I38022 hypot 432
429610 AB024937 Hs 211092 LUNX protein, PLUNC (palate lung and nas 432
453439 AI572438 Hs 32976 guanine nucleotde binding protein 4 431
407366 AF026942 Hs 17518 gb Homo sapiens clg33 mRNA, partial sequ 430
402802 NM.001397 Homo sapiens endothelm conver 430
402408 NM.030920* Homo sapiens hypothetcal pro 430
438321 AA576635 Hs 6153 CGI-48 protein 429
409435 AI810721 Hs 95424 ESTs 427
446440 AV658411 Hs 42656 KIAA1681 protein 425
432350 NM 005865 Hs 274407 protease, seπne, 16 (thymus) 425
419926 AW900992 Hs 93796 DKFZP586D2223 protein 422
407235 D20569 Hs 169407 SAC2 (suppressor of actn mutations 2, y 421
432140 AK000404 Hs 272688 hypothetical protein FLJ20397 420
428479 Y00272 Hs 334562 cell division cycle 2, G1 to S and G2 to 420
413582 AW295647 Hs 71331 hypothetical protein MGC5350 420
421928 AF013758 Hs 109643 polyadenylate binding protein Interactin 419
428728 NM 016625 Hs 191381 hypothetical protein 418
424001 W67883 Hs 137476 paternally expressed 10 417
441362 BE614410 Hs 23044 RAD51 (S cerevisiae) homolog (E coll Re 417
427658 H61387 Hs 30868 nogo receptor 417
450325 AI935962 Hs 91973 ESTs 416
452279 AA286844 hypothetical protein FLJ13164 4 15
408035 NM 006242 Hs 42215 protein phosphatase 1, regulatory subuni 414
414696 AF002020 Hs 76918 Niemann Pick disease, type C1 410
422576 BE548555 Hs 118554 CGI 83 protein 410
401558 ENSP00000220478* SECRETOGRANIN III 410
431585 BE242803 Hs 262823 hypothetical protein FLJ10326 410
456977 AK000252 Hs 169758 hypothetical protein FLJ20245 410
423493 AI815965 Hs 129683 ublquitin conjugating enzyme E2D 1 (homo 409
428654 NM 012091 Hs 188661 adenoslne deaminase, tRNA specific 1 407
416402 NM 000715 Hs 1012 complement component 4-blnding protein, 405
433077 AA314262 Hs 289008 YDD19 protein 405
430454 AW469011 Hs 105635 ESTs 405
440074 AA863045 Hs 10669 ESTs, Weakly slmilarto T00050 hypothet 404
433447 U29195 Hs 3281 neuronal pentraxln II 404
409799 D11928 Hs 76845 phosphosenne phosphatase like 403
436291 BE568452 Hs 344037 protein regulator of cytokinesis 1 403
407244 M10014 fibππogen, gamma polypeptide 401
452256 AK000933 Hs 28661 Homo sapiens cDNA FLJ10071 fis, clone HE 400
411305 BE241596 Hs 69547 myelin basic protein 399
418113 A1272141 Hs 83484 SRY (sex determining region Y) box 4 396
423175 W27595 Hs 347310 hypothetical protein FLJ14627 395
433388 AI432672 Hs 288539 hypothetical protein FLJ22191 393
440006 AK000517 Hs6844 NALP2 protein, PYRIN Containing APAF1-II 391
450193 AI916071 Hs 15607 Homo sapiens Fanconi anemia complementat 391
439453 BE264974 Hs 6566 thyroid hormone receptor interactor 13 391
400277 Eos Control 390
416498 U33632 Hs 79351 potassium channel subfamily K member 1 390
446999 AA151520 hypothetical protein MGC4485 390
407355 AA846203 Hs 193974 ESTs, WeaklysimliartoALUI.HUMAN ALU S 390
432201 AI538613 Hs 298241 Transmembrane protease, seππe 3 387
408670 AF160967 Hs 46784 potassium large conductance calcium act 385
409151 AA306105 Hs 50785 SEC22, vesicle trafficking protein (S c 385
422956 BE545072 Hs 122579 ECT2 protein (Epithelial cell transformi 385
426501 AW043782 Hs 293616 ESTs 385
430387 AW372884 Hs 240770 nuclear cap binding protein subunit 2, 2 383
421437 AW821252 Hs 104336 hypothetical protein 382
426451 AI908165 Hs 169946 GATA-biπdlπg protein 3 (T cell receptor 381
418329 AW247430 Hs 84152 cystathionlne beta synthase 380
428227 AA321649 Hs 2248 small Inducible cytokine subfamily B (Cy 380
404632 NM.022490 Homo sapiens hypothetcal prot 380
411704 AI499220 Hs 71573 hypothetical protein FLJ10074 380
404571 NM.015902* Homo sapiens progestn Induce 380
434834 AF156774 Hs 324020 1 acylglycerol 3 phosphate O acyltransfe 377
441553 AA281219 Hs 121296 ESTs 376
407300 AA102616 Hs 120769 gb zn43e07 s1 Stratagene HeLa cell s393 375
411598 BE336654 Hs 70937 H3 hlstone family, member A 375
453900 AW003582 Hs 226414 ESTs, Weakly slmilarto ALU8.HUMAN ALU S 375
418304 AA215702 gb zr97g10 r1 NCI.CGAP.GCBI Homo sapiens 375
425842 AI587490 Hs 159623 NK-2 (Drosophila) homolog B 375
405558 Target Exon 375
438869 AF075009 gb Homo sapiens full length Insert cDNA 374
400409 AF153341 Homo sapiens winged hellx/forkhead trans 373
432840 AK001403 Hs 279521 hypothetical protein FLJ20530 372
406685 M18728 gb Human nonspecific crossreacting antlg 370
415621 AI648602 Hs 55468 ESTs 370
443687 F13040 KIAA1228 protein 370
421340 F07783 Hs 1369 decay accelerating factor for complement 370
422440 NM 004812 Hs 116724 aldo keto reductase family 1, member B10 368
415339 NM 015156 Hs 78398 KIAA0071 protein 367
409757 NM.001898 Hs 123114 cystatn SN 365
420390 AA330047 Hs 191187 ESTs 365 442772 AW503680 Hs5957 Homo sapiens clone 24416 mRNA sequence 365
414670 BE409525 Hs902 neurofibromin 2 (bilateral acoustic neur 365
416198 H27332 Hs99598 hypothetical protein MGC5338 365
425782 U66468 Hs 159525 cell growth regulatory with EF-hand doma 365
417601 NM 014735 Hs 82292 KIAA0215 gene product 363
435854 AJ278120 Hs4996 putative ankynn repeat containing prate 363
448826 AI580252 Hs 293246 ESTs, Weakly simllarto putatve p150 (H 362
425242 D13635 Hs 155287 KIAA001O gene product 361
408452 AA054683 Hs 192455 ESTs, Weakly slmilarto ALU7.HUMAN ALU S 360
434808 AF155108 Hs256150 NY REN 41 antigen 360
418478 U38945 HS1174 cyclin dependent kinase Inhibitor 2A (me 360
429687 AI675749 Hs 211608 nucleopoπn 153kD 356
431448 AL137517 Hs 306201 hypothetical protein DKFZp56401278 355
417378 R57256 Hs 82037 TATA box binding protein (TBP) associate 355
453160 AI263307 H2B hlstone family, member L 355
422094 AF129535 Hs 272027 F box only protein 5 355
438118 AW753311 ESTs 355
442861 AA243837 Hs 57787 ESTs 355
448186 AA262105 Hs4094 Homo sapiens cDNA FLJ14208 fis, clone NT 355
432329 NM 002962 Hs 2960 S100 calcium-binding protein A5 355
449318 AW236021 Hs78531 Homo sapiens, Simllarto RIKEN cDNA 5730 355
443450 N66045 Hs 133529 ESTs 355
422168 AA586894 Hs 112408 S100 calcium binding protein A7 (psonas 355
409542 AA503020 Hs 36563 hypothetical protein FLJ22418 354
423250 BE061916 Hs 125849 chromosome 8 open reading frame 2 354
447349 AI375546 gb tc23d04 x1 Soares_total_fetus_Nb2HF8_ 352
424273 W40460 Hs 144442 phospholipase A2, group X 352
444735 BE019923 Hs243122 hypothetical protein FLJ13057 slmilarto 351
453785 AI368236 Hs 283732 ESTs, Moderately similar to ALU1.HUMAN A 350
406081 Target Exon 350
411096 U80034 Hs 68583 mitochondrial intermediate peptidase 350
409902 AI337658 Hs 156351 ESTs 350
458621 AI221741 Hs 117777 ESTs 349
435664 AI032087 Hs 269819 ESTs 348
438714 AA814859 ESTs 346
415947 U04045 Hs78934 muts (E coli) homolog 2 (colon cancer, 346
409731 AA125985 Hs56145 thymosin, beta, identified In neuroblast 345
453941 U39817 Hs36820 Bloom syndrome 345
442353 BE379594 Hs49136 ESTs, Moderately similar to ALU7.HUMAN A 345
410206 NM 003826 Hs 60415 N ethylmalelmlde sensitive factor attach 345
408527 AL135018 Hs 33074 Homo sapiens clone IMAGE 3606519 mRNA, 344
415079 R43179 Hs 22895 hypothetical protein FLJ23548 344
420005 AW271106 Hs 133294 ESTs 343
425354 U62027 Hs 155935 complement component 3a receptor 1 343
442118 AA976718 Hs202242 ESTs 340
434844 AF157116 Hs 22350 hypothetical protein LOC56757 340
426931 NM 003416 Hs 2076 zinc finger protein 7 (KOX 4 clone HF 1 340
415263 AA948033 Hs 130853 ESTs 340
412863 AA121673 Hs 59757 zinc finger protein 281 340
454453 AW752781 hypothetical protein FLJ12614 slmilarto 338
441128 AA570256 ESTs, Weakly simllarto T23273 hypothet 338
422938 NM.001809 Hs 1594 centromere protein A (17kD) 338
443180 R15875 Hs258576 claudin 12 337
428839 AI767756 Hs 82302 Homo sapiens cDNA FLJ14814 fis clone NT 337
411605 AW006831 ESTs 337
413719 BE439580 Hs75498 small Inducible cytokine subfamily A (Cy 336
444371 BE540274 Hs239 forkhead boxMI 335
430188 AL049242 Hs 234794 Homo sapiens mRNA, cDNA DKFZp564B083 (fr 335
408101 AW968504 Hs 123073 CDC2 related protein kinase 7 335
425769 U72513 Hs 159486 Human RPL13-2 pseudogene mRNA, complete 335
451806 NM 003729 Hs 27076 RNA 3'-termlnal phosphate cyclase 335
410166 AK001376 Hs 59346 hypothetical protein FLJ 10514 335
442326 H92962 Hs 124813 hypothetical protein MGC14817 335
442660 AW138174 Hs 130651 ESTs 335
446054 AB014537 Hs 13604 KIAA0637 gene product 334
427581 NM 014788 Hs 179703 KIAA0129 gene product 333
433556 W56321 Hs 111460 calclum/calmodulln dependent protein kin 333
448552 AW973653 Hs 20104 hypothetical protein FLJ00052 333
434203 BE262677 Hs 283558 hypothetical protein PR01855 333
402496 Target Exon 332
432169 Y00971 Hs 2910 phosphoπbosy! pyrophosphate synthetase 330
410174 AA306007 Hs 59461 DKFZP434C245 protein 330
424332 AA338919 Hs 101615 ESTs 330
412530 AA766268 Hs 266273 hypothetical protein FLJ13346 330
425018 BE245277 Hs 154196 E4F transcπpton factor 1 330
430187 AI799909 Hs 158989 ESTs 330
440138 AB033023 Hs 318127 hypothetical protein FLJ10201 330
444743 AA045648 Hs 301957 nudlx (nucleoside dlphosphate linked mol 330
415992 C05837 Hs 145807 hypothetical protein FLJ13593 330
400297 AI127076 Hs306201 hypothetical protein DKFZp56401278 329
442108 AW452649 Hs 166314 ESTs 328
410762 AF226053 Hs66170 HSKM B protein 326
420552 AK000492 Hs98806 hypothetical protein 325
442152 R39246 Hs 239666 Homo sapiens cDNA FLJ13495 fis, clone PL 325
422420 U03398 Hs 1524 tumor necrosis factor (ligand) superfami 325
435532 AW29148B Hs 117305 Homo sapiens, clone IMAGE 3682908, mRNA 325 436643 AA757626 Hs 10941 ESTs, Weakly simllarto IPP1.HUMAN PROTE 325
433183 AF231338 Hs 222024 transcnpton factor BMAL2 325
427521 AW973352 ESTs 325
411945 AL033527 Hs 92137 L myc-2 protein (MYCL2) 325
444381 BE387335 Hs 283713 hypothetical protein BC014245 324
430335 D80007 Hs 239499 KIAA0185 protein 324
438525 AW368528 Hs 100855 ESTs 324
400247 Eos Control 323
427621 BE621182 Hs 179882 hypothetical protein FLJ12443 322
418338 NM 002522 Hs 84154 neuronal pentraxln I 321
448686 AA158659 Hs 334712 hypothetical protein FLJ14744 320
450728 AW162923 Hs 25363 presenilin 2 (Alzheimerdisease 4) 320
426581 AB040956 Hs 135890 KIAA1523 protein 320
442179 AA983842 Hs 333555 chromosome 2 open reading frame 2 320
422536 AA311915 Hs 187726 gb EST182621 Jurkat T-cells VI Homo sapl 320
449704 AK000733 Hs 23900 GTPase activating protein 320
448595 AB014544 Hs 21572 KIAA0644 gene product 320
442592 BE566623 Hs 29899 ESTs, Weakly similar to G02075 transcπp 319
452994 AW962597 Hs 31305 KIAA1547 protein 319
426699 AA383337 Hs 121269 ESTs 318
427719 AI393122 Hs 134726 ESTs 317
418836 AI655499 Hs 161712 BMP-R1B 317
410619 BE512730 HS 65114 keratin 18 316
414271 AK000275 Hs 75871 protein kinase C binding protein 1 315
452833 BE559681 Hs 30736 KIAA0124 protein 315
452827 AI571835 Hs 55468 ESTs 314
430462 AI584156 Hs 105640 Homo sapiens, clone IMAGE 4139775, mRNA, 314
449145 AI632122 Hs 198408 ESTs 314
453902 BE502341 Hs 3402 ESTs 313
420982 AW576160 Hs 100729 KIAA0692 protein 313
425529 NM 014656 Hs 158282 KIAA0040 gene product 313
430289 AK001952 Hs 238039 hypothetical protein FLJ11090 313
413413 D82520 zinc finger protein 36 (KOX 18) 311
432728 NM 006979 Hs 278721 HLA class ll region expressed gene KE4 310
420090 AA220238 Hs 94986 πbonuclease P (38kD) 310
446715 AI337735 Hs 173919 ESTs, Moderately similar to ZN91.HUMAN Z 310
424539 L02911 Hs 150402 Act™ A receptor, type I (ACVR1) (ALK 310
443054 AI745185 Hs 84520 yes-associated protein 65 kDa 310
425641 D79758 Hs 14355 Homo sapiens cDNA FLJ13207 fis, clone NT 310
423642 AW452650 Hs 157148 hypothetical protein MGC13204 310
422005 BE266556 Hs 110702 Homo sapiens mRNA, cDNA DKFZp761E212 (fr 310
426108 AA622037 Hs 166468 programmed cell death 5 308
415632 U67085 Hs 78524 TcD37 homolog 308
426227 U67058 Hs 154299 Human pratelnase activated receptor-2 mR 307
425649 U30930 Hs 158540 UDP glycosyltransferase 8 (UDP-galactose 307
447541 AK000288 Hs 188O0 hypothetical protein FLJ20281 307
433323 AA805132 Hs 159142 ESTs 307
420522 AW957137 Hs 98541 hypothetical protein 307
450256 AA286887 Hs 24724 MFH amplified sequences with leuclne nc 306
429978 AA249027 ribosomal protein S6 306
403011 ENSP00000215330* Probable seπne/threonl 305
401203 Target Exon 305
417975 AA641836 Hs 30085 hypothetcal protein FLJ23186 305
410507 AA355288 transitional epithelia response protein 305
404440 NM.021048 Homo sapiens melanoma antigen, 305
419865 NM 007020 Hs 93502 U1-snRNP binding protein homolog (70kD) 305
410561 BE540255 Hs 6994 Homo sapiens cDNA FLJ22044 fis, clone H 305
430066 AI929659 Hs 237825 signal recognition particle 72kD 305
425322 U63630 Hs 155637 protein kinase, DNA activated, catalytc 305
412715 NM 000947 Hs 74519 pnmase, polypeptde 2A (58kD) 304
442530 AI580830 Hs 176508 Homo sapiens cDNA FLJ14712 fis, clone NT 304
406690 M29540 Hs 220529 carcinoembryonic antgen related cell ad 303
424163 NM 007071 Hs 142245 HERV-H LTR associating 3 303
450447 AF212223 Hs 25010 hypothetical protein P15-2 303
447444 AK000318 Hs 18616 hypothetcal protein FLJ20311 302
429903 AL134197 Hs 93597 cyclin dependent kinase 5, regulatory su 302
435472 AW972330 Hs 283022 triggenπg receptor expressed on myeloid 301
426572 AB037783 Hs 170623 hypothetical protein FLJ11183 300
426215 AW963419 Hs 155223 stannlocalcln 2 300
441102 AA973905 Intermediate filament protein syncoilln 300
444165 AL137443 Hs 10441 hypothetical protein FLJ11236 300
425673 R70318 Hs 339730 ESTs 300
442619 AA447492 Hs 20183 ESTs, Weakly similar to AF164793 1 prate 300
413832 AI913647 Hs 131886 Homo sapiens cDNA FLJ22113 fis, clone H 300
421515 Y11339 Hs 105352 GalNAc alpha-2, 6-sialyltransferase I, I 300
420610 AI683183 Hs 99348 distal-less homeo box 5 300
401435 C14000397* gl|7499898|plr||T33295 hypoth 300
422771 NM 012318 Hs 120165 leuclne zlpper-EF-hand containing transm 300
454293 H49739 Hs 134013 ESTs, Moderately simllarto HK61.HUMAN H 299
425465 L18964 Hs 1904 protein kinase C, lota 298
429183 AB014604 Hs 197955 KIAA0704 protein 297
448789 BE539108 Hs 22051 hypothetical protein MGC15548 297
429084 AJ001443 Hs 195614 splicing factor 3b, subunlt 3, 130kD 297
431197 AL038596 Hs 250745 polymerase (RNA) III (DNA directed) (62k 296
436167 AA705651 Hs 25087 ESTs 296
418203 X54942 Hs 83758 CDC28 protein kinase 2 296 451071 AW138807 Hs 204939 ESTs, Highly similar to A54677 homeotic 295
420362 U79734 Hs 97206 huntngtln interacting protein 1 295
442875 BE623003 Hs 23625 Homo sapiens clone TCCCTA00142 mRNA sequ 295
437389 AL359587 Hs 271586 hypothetical protein DKFZp762M115 294
418941 AA452970 Hs 239527 E1B 55kDa associated protein 5 294
439375 AA689526 Hs 344249 steroid dehydrogenase homolog 294
411975 AI916058 Hs 144583 3UTRof dead nnger (Drosophila) like 293
439574 AI469788 ESTs 293
417348 AI940507 Hs 318526 hypothetical protein FLJ12661 293
447155 AA100605 Hs 121557 ESTs, Weakly slmilarto DP1.HUMAN POLYPO 293
420956 AA351584 Hs 100543 Homo sapiens clone 24505 mRNA sequence 292
419705 AW368634 Hs 154331 ESTs 292
425159 NM 004341 Hs 154868 carbamoyl phosphate synthetase 2, aspart 292
416902 AA375634 Hs 288974 hypothetical protein FLJ 12528 291
407242 M18728 gb Human nonspecific crossreacting antig 291
446880 AI811807 Hs 108646 Homo sapiens cDNA FLJ14934 fis, clone PL 291
406581 Target Exon 290
404607 Target Exon 290
401093 C12000586* gι|6330167|db]|BAA864771| (A 290
421247 BE391727 Hs 102910 general transcription factor IIH, polype 290
405366 NM 003371* Homo sapiens vav 2 oncogene ( 290
418700 AI963808 Hs 86970 ESTs, Moderately similar to ALU5.HUMAN A 290
417288 AI984792 Hs 108812 hypothetical protein FLJ22004 290
419752 AA249573 Hs 152618 ESTs, Moderately similar to ZN91.HUMAN Z 290
450375 AA009647 a dismtegπn and metalloprotelnase doma 290
419497 NM 006410 Hs 90753 Tat interacting protein (30kD) 290
423849 AL157425 Hs 133315 Homo sapiens mRNA, cDNA DKFZp761J1324 (f 290
452909 NM 015368 Hs 30985 pannexin 1 290
430294 A1538226 Hs 32976 guanine nucleotde binding protein 4 290
414004 AA737033 Hs 7155 similar to thymldylate kinase family LPS 289
439680 AW245741 Hs 58461 ESTs, Weakly similar to A35659 krueppel 289
432908 AI861896 ESTs 289
408296 AL117452 Hs 44155 DKFZP586G1517 protein 288
450065 AL050107 Hs 24341 transcriptional co activator with PDZ bi 288
431770 BE221880 Hs 268555 5'-3 exoπbonuclease 2 287
431933 AI187057 Hs 132554 ESTs 287
424954 NM 000546 Hs 1846 tumor protein p53 (LI Fraumeni syndrome) 287
423771 AF053004 Hs 132781 class I cytokine receptor 287
449976 H06350 Hs 135056 Human DNA sequence from clone RP5 850E9 287
410442 X73424 Hs 63788 propionyl Coenzyme A carboxylase, beta p 287
423165 AI937547 Hs 124915 hypothetical protein MGC2601 287
445704 AI493742 Hs 167700 ESTs, Moderately similar to I38022 hypot 286
407198 H91679 gb yv04a07 s1 Soares fetal liver spleen 286
412942 AL120344 Hs 75074 mltogen activated protein kinase actvat 285
432229 AW290976 Hs 143587 ESTs 285
430452 AI888450 Hs 174644 hypothetical protein FLJ21669 285
422805 AA436989 Hs 121017 H2A hlstone family, member A 285
443614 AV655386 Hs 7645 fibrinogen, B beta polypeptide 285
429370 C19097 Hs 89709 glutamate-cysteine ligase, modtasubu 285
428829 R14050 Hs 194051 Homo sapiens mRNA, cDNA DKFZp566B213 (fr 284
411285 AI733766 Hs 69429 Homo sapiens IMAGE 512024 clone, mRNA 284
415402 AA164687 Hs 177576 mannosyl (alpha-1,3 ) glycoprotein beta 284
414821 M63835 Hs 77424 Fc fragment of IgG, high affinity la re 283
446595 T57448 Hs 15467 hypothetical protein FLJ20725 283
442643 U82756 PRP4/STKΛVD splicing factor 283
428438 NM 001955 Hs 2271 eπdothelin 1 282
441024 AW081530 Hs 268231 ESTs 282
453005 AW055308 Hs 31803 ESTs, Weakly slmilarto N WASP [H sapien 282
420851 AA281062 Hs 29493 hypothetical protein FLJ20142 282
412482 AI499930 Hs 334885 mitochondnal GTP binding protein 281
408633 AW963372 Hs 46677 PRO2000 protein 281
421077 AK000061 Hs 101590 hypothetical protein 281
433730 AK002135 Hs 3542 hypothetical protein FLJ11273 281
433867 AK000596 Hs 3618 hippocalcln like 1 281
433701 AW445023 Hs 15155 ESTs 281
425849 AJ000512 Hs 296323 serum/glucocorticold regulated kinase 281
433285 AW975944 Hs 237396 ESTs 281
407634 AW016569 Hs 136414 UDP-GlcNAc betaGal beta 1,3-N-acetylgIuc 281
457819 AA057484 Hs 35406 FLJ20522 Hypothetcal protein FLJ20522 281
426925 NM 001196 Hs 315689 Homo sapiens cDNA FLJ22373 fis, clone H 280
416406 D86961 Hs 79299 lipoma HMGIC fusion partner like 2 280
419544 AI909154 gb QV BT200-010499 007 BT200 Homo sapien 280
428134 AA421773 Hs 161008 ESTs 280
436211 AK001581 Hs 334828 hypothetical protein FLJ10719, KIAA1794 280
432006 AL137382 Hs 272320 Homo sapiens mRNA, cDNA DKFZp434L1226 (f 280
428758 AA433988 Hs 98502 CA125 antigen, mucln 16 280
422358 AL133030 Hs 115429 Homo sapiens mRNA for KIAA1666 protein, 279
452834 AI638627 Hs 105685 KIAA1688 protein 278
411908 L27943 Hs 72924 cytldlne deamlnase 278
453968 AA847843 Hs 62711 High mobility group (nonhlstone chromoso 277
431865 AA521106 Hs 136375 ESTs, Weakly simllarto S65824 reverse t 277
435937 AA830893 Hs 119769 ESTs 277
434263 N34895 Hs 79187 ESTs 276
434067 H18913 Hs 124023 Homo sapiens cDNA FLJ14218 fis, clone NT 275
415451 H19415 Hs 268720 ESTs, Moderately slmilarto ALU1 HUMA A 275
444185 AW298350 Hs 113602 ESTs 275 445873 AA250970 Hs 251946 poly(A)-binding protein, cytoplasmlc 1-1 275
411630 U42349 Hs 71119 Putatve prostate cancer tumor suppresso 275
453775 NM 002916 Hs 35120 replication factor C (activator 1 ) 4 (37 275
407771 AL138272 Hs 1600 ESTs 275
423492 AF020761 Hs 129683 ubiquitln-conjugating enzyme E2D 1 (homo 275
413063 AL035737 Hs 75184 chitnase 3 like 1 (cartilage glycoprote 274
431130 NM 006103 Hs 2719 HE4, epldidymis specific, whey-acldlc pr 274
421654 AW163267 Hs 106469 suppressor of varl (S cerevisiae) 3 like 274
409430 R21945 Hs 346735 splicing factor, arglnlne/seπne-πch 5 274
438533 AI440266 Hs 170673 ESTs, Weakly similar to T24832 hypothet 274
443209 AI040125 Hs 150521 ESTs 273
409439 AW390511 Hs 288862 Homo sapiens cDNA FLJ21260 fis, clone C 273
424511 BE300512 Hs 193557 ESTs, Moderately similar to ALU7.HUMAN A 273
443162 T49951 Hs 9029 DKFZP434G032 protein 273
455601 AI368680 Hs816 SRY (sex determining region Y) box 2 273
455286 BE144384 gb MR0-HT0166 191199 004 c11 HT0166 Homo 273
453751 R36762 Hs 101282 Homo sapiens cDNA FLJ21238 fis, clone C 273
424308 AW975531 Hs 154443 mlnlchromosome maintenance deficient (S 273
422963 M79141 Hs 13234 sphlngoslne 1-phosphate phosphohydrolase 272
426174 AA547959 Hs 115838 Homo sapiens similar to Echinoldin (LOC1 272
439210 AA641928 Hs 194071 ESTs, Weakly similar to unnamed protein 272
410082 AA081594 Hs 158311 Musashl (Drosophila) homolog 1 271
417454 NM 000202 Hs 172458 Iduronate 2-sulfatase (Hunter syndrome) 271
427083 NM 006363 Hs 173497 Sec23 (S cerevlslae) homolog B 271
448877 AI583696 Hs 253313 ESTs 270
400240 Eos Control 270
430881 NM 000809 Hs 248112 gamma-aminobutyrlc acid (GABA) A recepto 270
443323 BE560621 Hs 9222 estrogen receptor binding site associate 270
432188 AI362952 Hs 2928 solute earner family 7 (cationic amino 270
455290 U75810 gb HSU75810 Human Homo sapiens cDNA clon 270
429782 NM 005754 Hs 220689 Ras GTPase-activatng protein SH3 domain 270
456759 BE259150 Hs 127792 delta (Drosophila) like 3 270
428816 AA004986 Hs 193852 ATP-blnding cassette, sub-family C (CFTR 270
406625 Y13647 Hs 119597 stearoyl CoA desaturasβ (delta 9 desatur 270
425236 AW067800 Hs 155223 stanniocalcin 2 269
429048 AI372949 Hs 44241 Homo sapiens cDNA FLJ21447 fis, clone C 269
404819 NM 002688* Homo sapiens peanut (Drosophi 268
423645 AI215632 Hs 147487 ESTs 268
440327 R12581 Hs 191146 ESTs 267
426746 J03626 Hs 2057 undine monophosphate synthetase (orotat 267
422283 AW411307 Hs 114311 CDC45 (cell division cycle 45, S cerevls 267
400880 NM.000611* Homo sapiens CD59 antgen p18 266
420440 NM 002407 Hs 97644 mammaglobln 2 266
452099 BE612992 Hs 27931 hypothetical protein FLJ10607 simllarto 266
413431 AW246428 Hs 75355 ublqultln conjugating enzyme E2N (homolo 266
459672 Z18867 Hs 326843 gb HSDHEGC03 Stratagene cDNA library Hum 265
447805 AW627932 Hs 302421 gemln4 265
429277 AW452016 Hs 127863 ESTs, Weakly similar to SFR4 HUMAN SPLIC 265
447673 AI823987 Hs 182285 ESTs 265
420210 AI557257 Hs 44811 ESTs 265
449570 AA001793 gb zh86c06 Soares fetal liver spleen 265
453878 AW964440 Hs 19025 DC32 265
436488 BE620909 Hs 261023 hypothetical protein FLJ20958 265
442275 AW449467 Hs 54795 Homo sapiens secretoglobin, family 3A, m 264
446839 BE091926 Hs 16244 mitotic spindle coiled coil related prot 264
413278 BE563085 Hs 833 Interferon-stimulated protein, 15 kDa 264
409235 AA188827 HS 7988 ESTs, Weakly slmilarto I38022 hypothet 264
412673 AL042957 Hs 31845 ESTs 264
446258 AI283476 Hs 263478 ESTs 264
439211 AI890347 Hs 271923 Homo sapiens cDNA FLJ22785 fis, clone K 264
415323 BE269352 Hs 949 neutrophil cytosolic fador 2 (65kD, chr 263
409703 NM 006187 Hs 56009 2'-5' ollgoadenylate synthetase 3 (100 k 263
410305 AF030409 Hs 62185 solute earner family 9 (sodium/hydrogen 263
423081 AF262992 Hs 123159 sperm associated antgen 4 262
458981 AW968318 Hs 285996 hypothetical protein FLJ23375 262
434540 NM 016045 Hs 3945 CGI-107 protein 260
411190 AA306342 Hs 69171 protein kinase C like 2 260
453392 U23752 Hs 32964 SRY (sex determining region Y)-box 11 260
436027 AI864053 Hs 39972 GM2 ganglloslde activator protein (GM2A) 260
433906 AI167816 Hs 43355 ESTs 260
415857 AA866115 Hs 127797 Homo sapiens cDNA FLJ11381 fis, clone HE 260
432723 D29677 Hs 3085 KIAA0054 gene product, Hellcase 260
408031 AA081395 Hs 42173 Homo sapiens cDNA FLJ10366 fis, clone NT 260
448663 BE614599 hypothetical protein MGC14797 260
427700 AA262294 Hs 180383 dual specificity phosphatase 6 260
437478 AL390172 Hs 317432 branched chain amlnotransferase 1, cytos 260
426514 BE616633 Hs 170195 bone morphogenetc protein 7 (osteogenlc 260
434826 AF155661 Hs 22265 pyruvate dehydrogenase phosphatase 260
442711 AF151073 Hs 8645 hypothetical protein 259
401197 ENSP00000229263*HSPC213 259
420802 U22376 Hs 1334 v-myb avlan myeloblastosls viral oncogen 259
437967 BE277414 Hs 5947 mel transforming oncogene (derived from 259
411423 AW845987 Hs 68864 ESTs, Weakly similar to phosphatidylsen 258
409262 AK000631 Hs 52256 hypothetical protein FLJ20624 258
433009 AA761668 gb nz24c08 s1 NCI.CGAP.GCBI Homo sapiens 258
423309 BE006775 Hs 126782 sushi-repeat protein 258 429950 AW081608 Hs 105053 ESTs 258
447334 AA515032 Hs 91109 ESTs 257
412935 BE267045 Hs 75064 tubulin specific chaperone c 257
412123 BE251328 Hs 73291 hypothetical protein FLJ10881 257
421307 BE539976 Hs 103305 Homo sapiens mRNA, cDNA DKFZp434B0425 (f 257
450671 AI356967 Hs 43086 ESTs, Weakly similar to A46010 X linked 256
451418 BE387790 Hs 26369 hypothetical protein FLJ20287 256
428450 NM 014791 Hs 184339 KIAA0175 gene product 255
412141 A1183838 Hs 48938 hypothetical protein FLJ21802 255
404580 tπchorhiπophalangeal syndrome 1 gene (T 255
444461 R53734 Hs 25978 ESTs, Weakly simllarto 2109260A B cell 255
428264 AA424839 Hs 98484 ESTs, Weakly simllarto ALU1.HUMAN ALU S 255
413374 NM.001034 Hs 75319 ribonucleotde reductase M2 polypeptide 255
436009 H57130 Hs 120925 ESTs 255
421433 AI829192 Hs 22380 ESTs 255
441224 AU076964 Hs 7753 calumenln 254
447197 R36075 gb yh88b01 s1 Soares placenta Nb2HP Homo 254
457579 AB030816 Hs 36761 HRAS like suppressor 254
410660 AI061118 Hs 65328 Fanconi anemia, complementation group F 254
447064 AB002350 Hs 17262 KIAA0352 gene product 254
419507 AW170425 Hs 87680 ESTs 253
422095 AI868872 Hs 282804 hypothetical protein FLJ 22704 253
449845 AW971183 Hs 6019 DnaJ (Hsp40) homolog, subfamily C, membe 253
443426 AF098158 Hs 9329 chromosome 20 open reading frame 1 253
440273 AI805392 Hs 325335 Homo sapiens cDNA FLJ23523 fis, clone L 253
440340 AW895503 Hs 125276 ESTs 253
418867 D31771 Hs 89404 msh (Drosophila) homeo box homolog 2 253
428484 AF104032 Hs 184601 solute carrierfamlly 7 (cationic amino 253
432586 AA568548 ESTs 253
406922 S70284 Hs 119597 gb stearoyl CoA desaturase [human, adlpo 252
424581 M62062 Hs 150917 catenin (cadheπn-associated protein), a 252
408393 AW015318 Hs 23165 ESTs 252
408949 AF189011 Hs 49163 putative nbonuclease III 252
449207 AL044222 Hs 23255 nuoleoponn 155kD 252
449444 AW818436 solute earner family 16 (monocarboxylic 252
441373 AI266421 Hs 120179 Homo sapiens cDNA FLJ22133 fis, clone H 251
451380 H09280 Hs 13234 ESTs 251
448641 R31845 Hs 21666 insulin like 4 (placenta) 251
428844 AW972635 Hs 301904 hypothetical protein FLJ12671 251
424259 AK001776 Hs 143954 hypothetical protein FLJ10914 250
442053 R35343 Hs 24968 Human DNA sequence from clone RP1-233G16 250
402102 Target Exon 250
409648 AW451449 Hs 57749 ESTs 250
416677 T83470 Hs 334840 ESTs, Moderately similar to I78885 seπn 250
446251 AW867156 Hs 282589 ESTs, Weakly simllarto I38022 hypothet 250
413472 BE242870 Hs 75379 solute carrierfamlly 1 (glial high affi 250
400298 AA032279 Hs 61635 six transmembrane epithelial antgen of 250
420807 AA280627 Hs 57846 ESTs 250
451722 H86374 Hs 40861 ESTs 250
438523 H66220 Hs 278177 ESTs 250
402812 NM.004930* Homo sapiens capping protein 249
426991 AK001536 Hs 214410 Homo sapiens cDNA FLJ10674 fis, clone NT 249
452092 BE245374 Hs 27842 hypothetical protein FLJ 11210 249
407881 AW072003 Hs 40968 heparan sulfate (glucosamine) 3 O-sulfot 249
402855 NM.001839* Homo sapiens calpomn 3, add 249
422809 AK001379 Hs 121028 hypothetical protein FLJ10549 249
410444 W73484 Hs 132554 gb zd54e04 s1 Soares_fetal_heart_NbHH19W 248
457292 AI921270 Hs 281462 hypothetical protein FLJ14251 248
408990 AL022395 Hs 49526 f-box and leuclne rich repeat protein 4 248
441085 AW136551 Hs 181245 Homo sapiens cDNA FLJ12532 fis, clone NT 248
449209 BE616830 Hs 294145 ESTs 248
439352 BE614347 Hs 169615 hypothetical protein FLJ20989 248
411979 X85134 Hs 72984 retnoblastoma binding protein 5 248
434474 AL042936 Hs 211571 holocytochrome c synthase (cytochrome c 247
431566 AF176012 Hs 260720 J domain containing protein 1 247
453507 AF083217 Hs 33085 WD repeat domain 3 247
432540 AI821517 Hs 105866 ESTs 247
420085 AI741909 Hs 44680 hypothetical protein FLJ20979 247
408761 AA057264 Hs 238936 ESTs, Weakly slmilarto (defilne not ava 247
417018 M16038 Hs 80887 v-yes-1 Ya aguchl sarcoma viral related 247
428878 AA436884 Hs 48926 ESTs 247
443257 AI334040 Hs 11614 HSPC065 protein 247
410503 AW975746 Hs 188662 KIAA1702 protein 247
411248 AA551538 Hs 69321 Homo sapiens cDNA FLJ14408 fis, clone HE 246
416984 H38765 Hs 80706 diaphorase (NADH/NADPH) (cytochrome b 5 246
414844 AA296874 Hs 77494 deoxyguanoslne kinase 246
452436 BE077546 Hs 31447 ESTs, Moderately similar to A46010 X lln 246
445266 BE222118 Hs 12479 associated molecule with the SH3 domain 245
422363 T55979 Hs 115474 replication factorC (activator 1) 3 (38 245
445994 NM 004724 Hs 13512 ZW10 (Drosophila) homolog, centromere/kl 245
410595 AW629223 Hs 64794 zinc finger protein 183 (RING finger, C3 245
438578 AA811244 ESTs 245
437748 AF234882 Hs 5814 suppression of tumoπgeπlclty 7 245
411402 BE297855 Hs 69855 NRAS related gene 245
406671 AA129547 Hs 285754 met proto oncogene (hepatocyte growth fa 245
418882 NM 004996 Hs 89433 ATP binding cassette, sub family C (CFTR 245 424081 NM 006413 Hs 139120 πbonuclease P (30kD) 245
439492 AF086310 Hs 103159 ESTs 245
409617 BE003760 Hs 55209 Homo sapiens mRNA, cDNA DKFZp434K0514 (f 245
413545 AA766632 Hs 119451 ESTs 245
422765 AW409701 Hs 1578 baculoviral IAP repeat containing 5 (sur 245
426251 M24283 Hs 168383 Intercellular adhesion molecule 1 (CD54) 245
428862 NM 000346 Hs 2316 SRY (sex determining region Y) box 9 (ca 245
439955 AW203959 Hs 149532 ESTs 245
431958 X63629 Hs 2877 cadheπn 3, type 1, P cadheπn (placenta 245
421768 AI923934 Hs 108112 hlstone fold protein CHRAC17, DNA polyme 244
410575 BE207480 Hs 6994 Homo sapiens cDNA FLJ22044 fis, clone H 244
413551 BE242639 Hs 75425 ubiqultn associated protein 244
438956 W00847 Hs 135056 Human DNA sequence from clone RP5 850E9 244
418340 NM 013286 Hs 84162 chromosome 3p21 1 gene sequence 244
441318 AI078234 ESTs 244
417386 AL037228 Hs 82043 D123 gene product 2 4
428970 BE276891 Hs 194691 retnolc acid Induced 3 (RAIG1), metabo 244
448072 AI459306 Hs 24908 ESTs 243
447397 BE247676 Hs 18442 E-1 enzyme 243
441659 BE564162 Hs 250820 hypothetical protein FLJ14827 243
440590 AI863446 Hs 266308 mosaic senne protease 243
422309 U79745 Hs 114924 solute earner family 16 (monocarboxylic 243
414747 U30872 Hs 77204 centromere protein F (350/400kD, mitosin 242
442961 BE614474 F box only protein 22 242
446950 AA305800 Hs 5672 hypothetical protein AF140225 242
421462 AF016495 Hs 104624 aquaponn 9 242
450251 BE080483 gb QV1 BT0630280200 086 a05 BT0630 Homo 242
450277 AI690071 Hs 283552 ESTs, Weakly simllarto unnamed protein 242
422150 AI867118 calpastatin 241
425371 D49441 Hs 155981 mesothelin 241
452826 BE245286 Hs 301636 peroxlsomal biogenesis factor 6 241
439708 AI761369 Hs 59584 hypothetical protein FLJ21144 241
422744 AW268803 Hs 119640 hBKLF for basic kruppel like factor 241
412783 BE276738 Hs 74578 DEAD/H (Asp Glu-Ala Asp/His) box polypep 241
418526 BE019020 Hs 85838 solute carrierfamlly 16 (monocarboxylic 240
452960 AK001335 Hs 31137 protein tyrosine phosphatase, receptor t 240
414368 W70171 Hs 75939 urldlne monophosphate kinase 240
409892 AW956113 HS7149 gb EST368183 MAGE resequences, MAGD Homo 240
442991 BE281238 Hs 8886 hypothetical protein FLJ20424 240
425216 U81504 Hs 155172 adaptor related protein complex 3, beta 240
443829 AI087954 Hs 23348 S phase kinase associated protein 2 (p45 240
442072 AI740832 Hs 12311 Homo sapiens clone 23570 mRNA sequence 240
412193 AI684467 Hs 144057 ESTs 240
408826 AF216077 Hs 48376 Homo sapiens clone HB 2 mRNA sequence 240
422631 BE218919 Hs 118793 hypothetical protein FLJ10688 240
422981 AF026445 Hs 122752 TATA box binding protein (TBP) associate 240
418330 BE409405 ESTs 240
434627 AI221894 Hs 39311 ESTs 240
418067 AI127958 Hs 83393 cystatn E/M 240
442426 AI373062 Hs 332938 hypothetical protein MGC5370 240
433561 BE540937 Hs 20104 hypothetical protein FLJ00052 239
422336 AI761322 Hs 115285 dihydrolipoamide S acetyltransferase (E2 239
431374 BE258532 Hs 251871 CTP synthase 239
437271 AL137445 Hs 28846 Homo sapiens mRNA, cDNA DKFZp5660134 (fr 239
409974 BE174106 Hs 225641 hypothetical protein FLJ13171 239
445921 AW015211 Hs 146181 ESTs 239
431310 AW327889 Hs 252433 Homo sapiens cDNA FLJ13794 fis, clone TH 239
435124 AA725362 Hs 120456 ESTs 238
401405 Target Exon 238
452234 AW084176 Hs 223296 ESTs, Weakly simllarto I38022 hypothet 238
415214 A1445236 Hs 125124 EphB2 238
404592 NM 022739* Homo sapiens E3 ublquitin llg 238
434378 AA631739 Hs 335440 EST 238
406203 Target Exon 238
442355 AA456539 Hs 8262 lysosomal associated membrane protein 2 238
425548 AA890023 Hs 1906 prolactn receptor 238
409132 AJ224538 Hs 50732 protein kinase, AMP-actvated, beta 2 no 237
404661 C9000306* gi|12737280|ref|XP_0066822) k 237
431127 U66618 Hs 250581 SWI/SNF related, matrix associated, act 237
453905 NM 002314 Hs 36566 LIM domain kinase 1 237
416114 AI695549 Hs 183868 glucuronldase, beta 237
413437 BE313164 Hs 75361 gene from NF2ΛnenlngIoma region of 22q12 237
418403 D86978 Hs 84790 KIAA0225 protein 237
419092 J05581 Hs 89603 mucln l, transmembrane 237
434094 AA305599 Hs 238205 hypothetical protein PRO2013 236
450800 BE395161 Hs 1390 prateasome (prosome, macropaln) subunit, 236
452323 W44356 Hs 292812 ESTs, Weakly similar to T33468 hypothet 236
411678 AI907114 Hs 71465 squalene epoxidase 235
414774 X02419 Hs 77274 plasmlnogen activator, urokiπase 235
421379 Y15221 Hs 103982 small Inducible cytokine subfamily B (Cy 235
448030 N30714 Hs 325960 membrane spanning 4 domains, subfamily A 235
454645 AW811928 gb RC2-ST0168 240300017 b02 ST0168 Homo 235
425368 AB014595 Hs 155976 cullin 4B 235
425212 AW962253 Hs 171618 ESTs 235
426098 NM 014906 Hs 166351 KIAA1072 protein 235
432281 AK001239 Hs 274263 hypothetical protein FLJ10377 235 418592 X99226 Hs 284153 Fanconl anemia, complementation group A 235
412043 BE156622 Hs 333371 Homo sapiens clone TA40 untranslated RN 235
431696 AA259068 Hs 267819 protein phosphatase 1, regulatory (inhib 235
451065 AW295132 Hs 222231 ESTs, Weakly similar to granule cell mar 235
416018 AW138239 Hs 78977 proproteln convertase subtilisin/kexin t 235
432226 AW182766 Hs 273558 phosphate cytidylyltransferase 1, cholin 235
425048 H05468 Hs 164502 ESTs 235
409187 AF154830 Hs 50966 carbamoyl-phosphate synthetase 1, mitoch 235
414629 AA345824 Hs 76688 carboxylesterase 1 (monocyte/macrophage 235
413010 AA393273 Hs 75133 transcription factor 6-lιke 1 (mitochond 235
416426 AA180256 Hs 210473 Homo sapiens cDNA FLJ 14872 fis, clone PL 235
441021 AW578716 Hs 7644 H1 histoπe family, mβmber2 235
435005 U80743 Hs 306094 tnnucleotide repeat containing 12 235
407204 R41933 Hs 140237 ESTs, Weakly simllarto ALU1.HUMAN ALU S 235
445654 X91247 Hs 13046 thioredoxin reductase 1 234
437682 AA476652 Hs 94952 Homo sapiens cDNA FLJ23371 fis, clone H 234
417333 AL157545 Hs 173179 bromodomain and PHD finger containing, 3 234
417831 H16423 Hs 82685 CD47 antigen (Rh-related antigen, Integr 234
453204 R10799 Hs 191990 ESTs 234
430791 AA486293 Hs 272068 ESTs, Weakly similar to ALU3.HUMAN ALU S 234
415752 BE314524 Hs 78776 putative transmembrane protein 234
432788 AA521091 Hs 178499 Homo sapiens cDNA FLJ23117 fis, clone L 234
429857 AF089897 Hs 294030 topolsomerase-related function protein 4 233
453857 AL080235 Hs 35861 Ras-induced senescence 1 (RIS1) 233
418372 AA311833 Hs 84318 replication protein A1 (70kD) 233
424755 AB033094 Hs 152925 KIAA1268 protein 233
432623 AA557351 Hs 152448 ESTs, Moderately similar to S14147 mult 233
434815 AF155582 Hs 46744 corel UDP-^alactose N-acetylgalactosamm 232
431183 NM 006855 Hs 250696 KDEL (Lys-Asp-Glu-Leu) endoplasmlc retic 232
409196 NM 001874 Hs 334873 carboxypeptdase M 232
426272 AW450671 Hs 189284 ESTs 231
447644 AW861622 Hs 108646 Homo sapiens cDNA FLJ14934 fis, clone PL 231
429276 AF056085 Hs 198612 G protein coupled receptor 51 231
456497 AW967956 Hs 123648 ESTs, Weakly slmilarto AF1084601 ubmu 230
439778 AL109729 Hs 99364 putative transmembrane protein 230
446237 AW270515 Hs 149596 Homo sapiens, Similar to RIKEN cDNA 2310 230
405411 ENSP00000252213 SODIUM BICARBONATE COTRA 230
426262 AI792141 Hs 196270 folate transporter/earner 230
400639 C10000999* gι|2143593|pιrj|S55277 annexi 230
424194 BE245833 Hs 169854 gb TCBAP1E1908 Pedlatπc pre-B cell acut 230
412661 N32860 Hs 24611 ESTs, Weakly similar to I54374 gene NF2 230
445523 Z30118 Hs 293788 ESTs, Moderately similar to unnamed prot 230
405705 C12000104*gι|4503519|ref|NP_0037451| e 230
420596 NM 002692 Hs 99185 polymerase (DNA directed), epsilon 2 230
429433 AA452899 Hs 213586 ESTs, Weakly slmilarto KIAA1353 protein 230
455540 BE080231 gb RC4-BT0629-120200-012-f11 BT0629 Homo 230
426088 AF038007 Hs 166196 ATPase, Class I, type 8B, member 1 230
414485 W27026 Hs 182625 VAMP (vesicle-associated membrane protei 230
426427 M86699 Hs 169840 TTK protein kinase 230
407633 NM.007069 Hs 37189 simllarto ratHREV107 230
437659 AB007944 Hs5737 KIAA0475 gene product 230
438510 AL080220 Hs 6285 DKFZP586P0123 protein 230
414178 AW957372 Hs 46791 ESTs, Weakly similar to I38022 hypothet 230
424339 BE257148 endoglycaπ 230
419594 AA013051 Hs 91417 topoisomerase (DNA) II binding protein 229
425424 NM 004954 Hs 157199 ELKL motif kinase 229
424649 BE242035 Hs 151461 embryonic ectoderm development 229
408839 AW277084 gb xp61h09 x1 NCI_CGAP_Ov39 Homo sapiens 229
414883 AA926960 CDC28 protein kinase 1 229
453454 AW052006 PRP4/STKΛVD splicing factor 229
446080 AI221741 Hs 117777 ESTs 229
450937 R49131 Hs 26267 ATP-dependant Interferon response protei 229
459241 AA032276 Hs 99010 ESTs, Moderately similar to T14342 NSD1 228
426788 U66615 Hs 172280 SWI/SNF related, matπx associated, act 228
417720 AA205625 Hs 208067 ESTs 228
417542 J04129 Hs 82269 progestagen-associated endometπal prote 228
456141 AI751357 Hs 288741 Homo sapiens cDNA FLJ22256 fis, clone H 228
425523 AB007948 Hs 158244 KIAA0479 protein 228
403055 C2002219* gi|12737280|reflXP_0066822| k 228
425707 AF115402 Hs 11713 E74-Iike factor 5 (ets domain transcript 228
418322 AA284166 Hs 84113 cyclln dependent kinase Inhibitor 3 (CDK 228
412505 AA974491 Hs 21734 ESTs 228
453863 X02544 Hs 572 orosomucold 1 228
410275 U85658 Hs 61796 transcπpton factor AP-2 gamma (activat 227
421535 AB002359 Hs 105478 phosphoribosylformylglyciπamldine syntha 227
451150 AI888124 Hs 285280 Homo sapiens cDNA FLJ22096 fis, clone H 227
423198 M81933 Hs 1634 cell division cycle 25A 227
407777 AA161071 Hs 71465 squalene epoxidase 227
451232 AI769922 Hs 20023 ESTs 227
430316 NM.000875 Hs 239176 Insulin-Ilke growth factor 1 receptor 227
400884 Target Exon 227
436608 AA628980 Hs 192371 down syndrome cπtcal region protein DS 226
434423 NM 006769 Hs 3844 LIM domain only 4 226
438613 C05569 Hs 243122 hypothetical protein FLJ13057 simllarto 226
421180 BE410992 Hs 258730 heme-regulated Initiation factor 2-alpha 226
456844 AI264155 Hs 152981 CDP-dlacylglycerol synthase (phosphatlda 226 422010 AA302049 Hs 31181 Homo sapiens cDNA FLJ23230 fis, clone C 226
440100 BE382685 Hs 158549 ESTs, Weakly similar to T2D3 HUMAN TRANS 225
445871 AI702901 Hs 145582 ESTs, Weakly simllarto FOR4 MOUSE FORMI 225
422955 AW967824 Hs 324237 ESTs 225
404877 NM.005365 Homo sapiens melanoma antigen, 225
401160 Target Exon 225
418764 N30531 Hs 42215 protein phosphatase 1, regulatory subuni 225
452243 AL355715 Hs 28555 programmed cell death 9 (PDCD9) 225
452206 AW340281 Hs 33074 Homo sapiens, clone IMAGE 3606519, mRNA, 225
423290 AA324130 Hs 27721 Wolf Hirschhom syndrome candidate 1-lik 225
428405 Y00762 Hs 2266 cholinerglc receptor, nlcotnlc, alpha p 225
413273 U75679 Hs 75257 stem-loop (hlstone) binding protein 225
426028 NM 001110 Hs 172028 a dislntegrin and metalloprotelnase doma 225
428028 U52112 Hs 182018 lnterieukin-1 receptor-associated kinase 225
427691 AW194426 Hs 20726 UDP-N-acetyl alpha D-galactosamlne polyp 224
429588 AI080271 ESTs 224
429966 BE081342 Hs 283037 HSPC039 protein 224
416655 AW968613 Hs 79428 BCL2/adenovirus E1B 19kD-lnteractlng pro 224
412452 AA215731 suppression of tumoπgenlcity 5 224
411580 AL080088 Hs 70877 DKFZP564K2062 protein 224
457653 AI820719 Hs 76853 DnaJ (Hsp40) homolog, subfamily A, membe 224
433002 AF048730 Hs 279906 cyclln T1 224
419362 N64116 Hs 24624 hypothetical protein FLJ21945 224
434340 AI193043 Hs 128685 ESTs, Weakly simllarto T17226 hypothet 224
420186 NM 015925 Hs 95697 liver-specific bHLH-Zip transcπptlon fa 224
430375 AW371048 Hs 93758 H4 hlstone family, memberH 223
448356 AL120837 Hs 20993 high glucose regulated protein 8 223
420554 AL133022 Hs 98845 Homo sapiens mRNA, cDNA DKFZp434l0121 (f 223
430016 NM 004736 Hs 227656 xenotropic and polytroplc retrovirus rec 223
418004 U37519 Hs 87539 aldehyde dehydrogenase 3 family, member 223
440457 BE387593 Hs 21321 Homo sapiens clone FLB9213 PR02474 mRNA, 222
439924 AI985897 Hs 125293 ESTs 222
415889 R24563 VPS10 domain receptor protein 222
421353 AW292857 Hs 255130 ESTs 222
413476 U25849 Hs 75393 add phosphatase 1, soluble 222
430355 NM 006219 Hs 239818 phospholnosιtιde-3 kinase, catalytc, be 222
442092 AW578669 hypothetical protein FLJ12439 222
426181 AA371422 Hs 334371 hypothetical protein MGC13096 222
450074 AI367213 Hs 14070 hypothetical protein FLJ14166 222
407930 AA045847 Hs 188361 Homo sapiens cDNA FLJ12807 fis, clone NT 222
424534 D87682 Hs 150275 KIAA0241 protein 221
432195 AJ243669 Hs 8127 KIAA0144 gene product 221
420734 AW972872 Hs 293736 ESTs 221
422390 AW450893 Hs 121830 ESTs, Weakly similar to T42682 hypothet 221
414761 AU077228 Hs 77256 enhancer of zeste (Drosophila) homolog 2 221
414915 NM 002462 Hs 76391 myxovirus (influenza) resistance 1, homo 221
418030 BE207573 Hs 83321 neuromedin B 221
424736 AF230877 Hs 152701 microtubule Interacting protein that ass 221
428788 AF082283 Hs 193516 B cell CLL/lyrnphoma lO 221
408681 AW953853 Hs 281462 ESTs, Weakly simllarto 138022 hypothet 221
419485 AA489023 Hs 99807 ESTs, Weakly simllarto unnamed protein 221
446627 AI973016 Hs 15725 hypothetical protein SBBI48 220
440704 M69241 Hs 162 insulin like growth factor binding prate 220
436905 N31273 Hs 42380 ESTs 220
454034 NM 000691 Hs 575 aldehyde dehydrogenase 3 family, member 220
459376 BE258770 Homo sapiens, clone IMAGE 3344506, mRNA, 220
444527 NM.005408 Hs 11383 small inducible cytokine subfamily A (Cy 220
403429 C3000329* gi|8922921lref|NP_060821 11 hy 220
416814 AW192307 Hs 80042 dollchyl P-Glc Man9GlcNAc2 PP dollchylgl 220
403154 NM.022780* Homo sapiens hypothetical pro 220
410434 AF051152 Hs 63668 toll-like receptor 2 220
425810 AI923627 Hs 31903 ESTs 220
417173 U61397 Hs 81424 ublquitn like 1 (sentπn) 220
437587 AI591222 Hs 72325 Human DNA sequence from clone RP1-187J11 220
423020 AA383092 Hs 1608 replication protein A3 (14kD) 220
429626 U36787 Hs 211571 holocytochrome c synthase (cytochrome c 220
417933 X02308 Hs 82962 thymidylate synthetase 220
436972 AA284679 Hs 25640 claudln 3 220
421977 W94197 Hs 110165 ribosomal protein L26 homolog 220
416658 U03272 Hs 79432 fibrlllln 2 (congenital contra ural ara 220
417750 AI267720 Hs 260523 synovial sarcoma, translocated to X chro 219
413281 AA861271 Hs 222024 transcπpton factor BMAL2 219
408150 BE620274 Hs 43112 Homo sapiens mRNA, cDNA DKFZp434B1620 (f 219
422134 AW179019 Hs 112110 mltochondπal πbosomal protein L42 219
410723 AA100683 basigln (OK blood group) 219
445786 AW629819 Hs 144502 hypothetical protein FLJ22055 219
449162 AI632740 Hs 10476 ESTs 219
416097 BE387371 Hs 118964 hypothetical protein FLJ20085 219
429343 AK000785 Hs 199480 Homo sapiens, Similar to epsln 3, clone 218
409456 U34962 Hs 54473 cardiac-specific homeo box 218
411734 AW374954 Hs 71779 Homo sapiens DNA from chromosome 19, cos 218
401833 Integπn-linked kinase associated senne 218
409139 AI681917 Hs 3321 ESTs, Highly similar to IRX1.HUMAN IROQU 218
446567 NM 007247 Hs 15384 AP1 gamma subunlt binding protein 1 218
440334 BE276112 HS 7165 zinc finger protein 259 217
406627 T64904 Hs 163780 ESTs 217 447842 AW160804 Hs 247302 twisted gastrolaton 217
417433 BE270266 Hs 82128 5T4 oncofetal traphoblast glycoprotein 217
428781 AF164799 Hs 193384 putatative 28 kDa protein 217
410512 AA085603 Hs 250570 hypothetical protein MGC3180 217
436995 AI160015 Hs 125489 ESTs 217
442577 AA292998 Hs 163900 ESTs 217
402322 Target Exon 217
429462 AI890356 Homo sapiens, clone IMAGE 3536432, mRNA, 217
412326 R07566 Hs 73817 small inducible cytokine A3 (homologous 217
426722 U53823 Hs 171952 occludin 217
406867 AA157857 Hs 182265 keratin 19 217
424399 AI905687 AI905687 IL BT095-190199-019 BT095 Homo 217
427709 AI631811 Hs 180403 STRIN protein 216
410627 AA181339 Hs 929 myosln, heavy polypeptide 7, cardiac mus 216
429901 AK000502 Hs 56237 hypothetical protein FLJ20495 216
440282 BE262386 clones 23667 and 23775 zinc finger prate 216
422975 AA347720 Hs 122669 KIAA0264 protein 216
427254 AL121523 Hs 97774 ESTs 216
444006 BE395085 Hs 10086 type I transmembrane protein Fn14 216
424921 AA348491 Hs 322456 hypothetical protein DKFZp761D0211 216
405204 NM.002086* Homo sapiens growth factor re 216
412988 BE046680 gb hn42h03 x1 NCI.CGAP.RDF2 Homo sapiens 215
444151 AW972917 Hs 128749 alpha methylacyl CoA racemase 215
417185 NM 002484 Hs 81469 nucleotide binding protein 1 (E coli Min 2 15
447229 BE617135 Hs 22612 hypothetical protein DKFZp566D1346 215
414727 BE466904 Hs 190162 gb hz28f03 x1 NCI CGAP GC6 Homo sapiens 215
435542 AA687376 ESTs 215
410307 AF022913 Hs 62187 phosphatdylinositol glycan class K 215
442611 BE077155 Hs 177537 hypothetical protein DKFZp761B1514 215
418849 AW474547 Hs 53565 Homo sapiens PIG M mRNA for maπnosyltran 215
418647 AA226198 gb nc26a07 s1 NCI.CGAP.Pr1 Homo sapiens 215
422330 D30783 Hs 115263 epiregulin 215
418437 AA771738 Hs 348000 ESTs Moderately similar to ALU5 HUMAN A 215
457100 AA417878 Hs 48401 ESTs, Moderately similar to ALU8.HUMAN A 215
407748 AL079409 Hs 38176 KIAA0606 protein SCN Clrcadian Osclllat 215
444070 NM 015367 Hs 10267 MIL1 protein 2 15
408901 AK001330 Hs 48855 hypothetical protein FLJ 10468 215
444927 AW016637 Hs 199425 ESTs 215
429986 AF092047 Hs 227277 sine oculis homeobox (Drosophila) homolo 215
430178 AW449612 Hs 152475 3 UTR of achaete scute complex (Drosoph 215
410252 AW821182 Hs 61418 microfibπllar-associated protein 1 2 15
447669 AL049985 Hs 19180 Homo sapiens mRNA, cDNA DKFZp564E122 (ft 215
437270 R18087 Hs 323769 cisplatin resistance related protein CRR 214
458809 AW972512 Hs 20985 sln3 associated polypeptide, 30kD 214
418057 NM 012151 Hs 83363 coagulation factor VIII associated (intr 214
415279 F04237 Hs 1447 glial tbnllary acidic protein 214
444418 AL034417 Hs 11169 Gene 33/Mιg 6 214
430301 AI902657 Hs 188662 KIAA1702 protein 214
447587 AW292139 Hs 115789 ESTs 214
442767 AI017208 Hs 131149 ESTs 214
425811 AL039104 Hs 159557 karyopheπn alpha 2 (RAG cohort 1 , Impor 214
458882 R34993 Hs 226666 ESTs, Moderately similar to I54374 gene 214
436854 AA749167 Hs 173911 ESTs 213
439588 AA838166 Hs 174644 hypothetical protein FLJ21669 2 13
416975 NM 004131 Hs 1051 granzyme B (granzyme 2, cytotoxic T-lymp 213
427715 BE245274 Hs 180428 KIAA1181 protein 213
415014 AW954064 Hs 24951 ESTs 213
417389 BE260964 Hs 82045 mldkine (neuπte growth promoting factor 213
449955 AI676010 Hs 224043 ESTs 2 13
448920 AW408009 Hs 22580 alkylglycerone phosphate synthase 213
419767 W73306 Hs 306668 Homo sapiens cD A FLJ 14089 fis, clone MA 213
427674 NM 003528 Hs 2178 H2B histone family, member Q 213
424765 AA428211 hypothetical protein FLJ14033 simllarto 213
439306 BE220199 WD40 protein Ciaol 213
416361 AW204907 Hs 6872 ESTs, Weakly similar to CA13.HUMAN COLLA 212
407792 AI077715 Hs 39384 putative secreted ligand homologous to f 212
421875 AA299607 Hs 98969 ESTs 212
422405 AA310278 ESTs 212
414907 X90725 Hs 77597 polo (Drosophla) like kinase 212
414602 AW630088 Hs 76550 Homo sapiens mRNA, cDNA DKFZp564B1264 (f 212
400203 Eos Control 212
427779 AA906997 Hs 180780 TERA protein 211
419667 AU077005 Hs 92208 a dislntegrin and metalloprotelnase doma 211
420460 AA262331 Hs 48376 Homo sapiens clone HB-2 mRNA sequence 211
447711 AI459554 Hs 161286 ESTs 211
413838 AV661185 Hs 75574 mltochondπal ribosomal protein L19 211
419373 NM 003244 Hs 90077 TG Interacting factor (TALE family homeo 211
419741 NM 007019 Hs 93002 ublqultin earner protein E2 C 211
452429 AK000149 Hs 29493 hypothetical protein FLJ20142 211
431797 BE169641 Hs 270134 hypothetical protein FLJ20280 211
421690 AW162667 Hs 106857 calblndin 2 (29kD, calretiπln) 211
446994 AV650435 Hs 16755 MBIP protein 211
424629 M90656 Hs 151393 glutamate cystelne ligase, catalytc sub 210
426216 N77630 Hs 13895 Homo sapiens cDNA FLJ 11654 fis, clone HE 210
403961 Target Exon 210
434170 AA626509 Hs 122329 ESTs 210 432734 AA837396 Hs 263925 LIS1-ιnteractιng protein NUDE1, rat homo 2 10
414998 NM 002543 Hs 77729 oxidised low density lipoproteln (lectin 2 10
426410 BE298446 Hs 305890 BCL2 like 1 2 10
412700 BE222433 ESTs, Weakly simllarto I38022 hypothet 2 10
418397 NM 001269 Hs 84746 chromosome condensatoπ 1 2 10
449249 T52285 Hs 193115 Homo sapiens mRNA for KIAA1764 protein, 2 10
447401 BE618582 Hs 97661 ESTs 210
433745 AF075320 Hs 28980 hypothetical protein FLJ14540 2 10
410232 AW372451 Hs 61184 CGI 79 protein 2 10
452335 AW188944 Hs 61272 ESTs 2 10
454427 AW605620 Hs 76064 ribosomal protein L27a 2 10
406740 AA577274 gb nm85g07 s1 NCI_CGAP_Co9 Homo sapiens 2 10
403969 ENSP00000034663 Zinc finger protein 131 2 10
408405 AK001332 Hs 44672 hypothetical protein FLJ10470 2 10
433160 AW207002 Hs 134342 TASP for tests-specific adπamydn sens 209
425118 AU076611 Hs 154672 methylene tetrahydrofolate dehydrogenase 209
448556 AW885606 Hs 5064 ESTs 209
428966 AF059214 Hs 194687 cholesterol 25 hydroxylase 209
447887 AA114050 Hs 19949 caspase 8, apoptosls-related cystelne pr 209
426820 U73328 Hs 172648 distal less homeobox 4 209
435538 AB011540 Hs 4930 low density lipoproteln receptor related 209
449008 AW578003 Hs 22826 tropomodulin 3 (ubiquitous) 209
419252 AW138434 Hs 129805 ESTs 208
401192 Target Exon 208
419152 L12711 Hs 89643 transketolase (Wernlcke Korsakoff syndro 208
453164 F33692 Hs 32018 SNARE associated protein snapln 208
426158 NM 001982 Hs 199067 v erb b2 aviaπ erythroblastc leukemia v 208
422616 BE300330 Hs 118725 selenophosphate synthetase 2 208
422684 BE561617 Hs 119192 H2A hlstone family, member Z 208
431630 NM.002204 Hs 265829 integnn, alpha 3 (antigen CD49C, alpha 208
414341 D80004 Hs 75909 KIAA0182 protein 208
456806 AI222298 Hs 140720 GSK 3 binding protein FRAT2 208
459646 AW883968 Hs 321190 gb QV3 OT0063 290300 135 c04 OT0063 Homo 208
454417 AI244459 Hs 110826 tnnucleotide repeat containing 9 208
442481 N99828 gb za32c04 r1 Soares fetal liver spleen 207
430677 Z26317 desmogleln 2 207
420319 AW406289 Hs 96593 hypothetical protein 207
448633 AA311426 Hs 21635 tubulin, gamma 1 207
417863 AB000450 Hs 82771 vaccinia related kinase 2 207
411263 BE297802 Hs 69360 klnesln-like 6 (mltotic ceπtromere-assoc 207
450157 AW961576 Hs 60178 ESTs 207
410491 AA465131 Hs 64001 Homo sapiens clone 25218 mRNA sequence 207
440594 AW445167 Hs 126036 ESTs 207
401832 Integnn linked kinase associated seπne 206
401797 Target Exon 206
443683 BE241717 Hs 9676 uncharacteπzed hypothalamus protein HT0 206
425474 Z48054 Hs 158084 peroxlsome receptor 1 206
433658 L03678 Hs 156110 Immunoglobulin kappa constant 206
452012 AA307703 Hs 279766 kinesin family member 4A 206
453331 AI240665 ESTs 206
410407 X66839 Hs 63287 carbonic anhydrase IX 206
414983 L17128 Hs 77719 gamma-glutamyl carboxylase 206
456465 M94065 Hs 94925 dihydroorotate dehydrogenase 206
446111 W56338 Hs 13880 CGI-143 protein 206
409190 AU076536 Hs 50984 sarcoma amplified sequence 206
446163 AA026880 Hs 25252 prolactn receptor 206
404029 NM.018936* Homo sapiens protocadheπn be 206
437108 AA434054 Hs 80624 hypothetical protein MGC2560 206
452110 T47667 Hs 28005 Homo sapiens cDNA FLJ11309 fis, clone PL 205
428753 AW939252 Hs 192927 hypothetical protein FLJ20251 205
427752 AA470687 Hs 104772 ESTs 205
410976 R36207 Hs 25092 hypothetical protein MGC10744 205
409960 BE261944 hexoklπase 1 205
452721 AJ269529 Hs 301871 solute earner family 37 (glycerol 3 pho 205
446269 AW263155 Hs 14559 hypothetical protein FLJ10540 205
411761 AI733848 Hs 71935 putative zinc finger protein from EUROIM 205
420942 H03514 Hs 15589 ESTs 205
408673 BE208517 ribosomal protein L37a 205
406709 AI355761 Hs 242463 keratin 8 205
447128 AI271898 cyclln K 205
449437 AI702038 Hs 100057 Homo sapiens cDNA FLJ22902 fis, clone K 205
416812 H91010 Hs 44940 ESTs 205
404831 C1002937* gl|7499208|plr||T20993 hypothe 205
408841 AW438865 Hs 256862 ESTs 205
410656 BE161335 Hs 321717 ESTs, Weakly slmilarto S22765 heterogen 205
418319 AW611703 Hs 190173 ESTs, Weakly simllarto A46010 X linked 205
400249 Eos Control 205
439092 AA830149 gb oc44f08 s1 NCI.CGAP.GCBI Homo sapiens 205
448390 AL035414 Hs 21068 hypothetical protein 205
440953 AI683036 Hs 124135 Homo sapiens cDNA FLJ 13051 fis, clone NT 205
427178 AA398866 Hs 97542 Homo sapiens tests-development related 205
401463 histone deacetylase 5 205
453849 N35321 Hs 278611 UDP-N acetyl alpha D-galactosamlne polyp 205
426172 AA371307 Hs 125056 ESTs 205
423871 AA331906 Hs 175596 gb EST35805 Embryo, 8 week I Homo sapien 205
418690 AK000052 Hs 87293 hypothetical protein FLJ20045 205 423248 AA380177 Hs 125845 nbulose 5 phosphate 3-eplmerase 205
427356 AW023482 Hs 97849 ESTs 205
435147 AL133731 Hs 4774 Homo sapiens mRNA, cDNA DKFZp761C1712 (f 205
415025 AW207091 Hs 72307 ESTs 205
437763 AA469369 Hs 5831 tissue inhibitor of metalloprotelnase 1 205
413916 N49813 Hs 75615 apolipoproteln C II 205
452177 AI863447 Hs 268180 gbtz48f01 x1 NCI CGAP Bm52 Homo sapien 205
407590 AI831258 ESTs 205
431250 BE264649 Hs 251377 taxol resistance associated gene 3 205
430750 Al 650360 Hs 100256 ESTs 205
448296 BE622756 Hs 10949 Homo sapiens cDNA FLJ14162 fis, clone NT 205
447211 AL161961 Hs 17767 KIAA1554 protein 205
412939 AW411491 Hs 75069 eukaryotic translation elongation factor 205
420309 AW043637 Hs 21766 ESTs, Weakly similar to ALU5.HUMAN ALU S 204
422321 AA906427 Hs 181035 hypothetical protein MGC11296 204
424287 AL133105 Hs 144633 hypothetical protein DKFZp434F2322 204
432878 BE386490 Hs 279663 Plnn 204
408113 T82427 Hs 194101 Homo sapiens cDNA FLJ20869 fis clone A 204
447973 AB011169 Hs 20141 simllarto S cerevlslae SSM4 204
410553 AW016824 Hs 272068 hypothetcal protein MGC14128 204
416990 AF124145 Hs 80731 autocnne motlity factor receptor 204
451273 NM 014811 Hs 26163 KIAA0649 gene product 204
412507 L36645 Hs 73964 EphA4 204
433257 AA613437 Hs 302743 hypothetical protein FLJ12543 204
443823 BE089782 Hs 9877 hypothetical protein 204
403532 NM 024638 Homo sapiens hypothetcal prot 204
437159 AL050072 Hs 306313 Homo sapiens mRNA cDNA DKFZp566E1346 (f 203
407813 AL120247 Hs 40109 KIAA0872 protein 203
440773 AA352702 Hs 37747 Homo sapiens, Slmilarto RIKEN cDNA 2700 203
424036 AA770688 H2A histone family, member L 203
409463 AI458165 Hs 17296 hypothetical protein MGC2376 203
445929 AI089660 Hs 323401 dpy 30 like protein 203
452046 AB018345 Hs 27657 KIAA0802 protein 203
443347 AI052543 Hs 133244 melanoma deπved leuclne zipper, extra π 203
405264 NM.030813* Homo sapiens suppressor of po 203
408756 AA524743 ESTs 203
417308 H60720 Hs 81892 KIAA0101 gene product 203
416391 AI878927 Hs 79284 mesoderm specific transcπpt (mouse) horn 203
453055 AW291436 Hs 31917 Homo sapiens, clone MGC 9658, mRNA, comp 203
427484 N32859 Hs 37288 nuclear receptor subfamily 1, group D, m 203
419852 AW503756 Hs 286184 hypothetical protein dJ551D25 203
432673 AB028859 Hs 278605 DnaJ (Hsp40) homolog, subfamily B, membe 203
424381 AA285249 Hs 146329 protein kinase Chk2 (CHEK2) 202
443826 AI214805 Hs 27232 ESTs 202
456258 AW976410 Hs 289069 Homo sapiens clone FLB3411 PRO0852 mRNA, 202
418105 AW937488 Hs 246381 ESTs, Weakly similar to FV1 MOUSE FRIEND 202
409445 AW341217 Hs 14139 ESTs, Weakly simllarto JC5314 CDC28/cdc 202
437016 AU076916 Hs 5398 guanine moπphosphate synthetase 202
449230 BE613348 melanoma cell adhesion molecule 202
424527 AW138558 Hs 334873 ESTs, Weakly slmilarto I54374 gene NF2 202
419239 AA468183 Hs 184598 Homo sapiens cDNA FLJ23241 fis, clone C 202
427982 NM 016156 Hs 181326 KIAA1073 protein 202
410855 X97795 Hs 66718 RAD54 (S cerevislae) like 202
437897 AA770561 Hs 146170 hypothetical protein FLJ22969 201
449000 U69560 Hs 3826 kelch like protein C3IP1 201
437435 AA249439 Hs 27027 hypothetical protein DKFZp762H1311 201
421757 Z20897 Hs 296259 paraoxonase 3 201
436238 AK002163 Hs 301724 hypothetical protein FLJ11301 201
436856 AI469355 Hs 127310 ESTs 201
432026 AA524545 Hs 224630 ESTs 201
407230 AA157857 Hs 182265 keratin 19 201
447701 BE619526 Hs 272068 hypothetical protein MGC14128 201
418583 AA604379 Hs 86211 hypothetical protein 201
408946 AW854991 Hs 255565 ESTs 201
419440 AB020689 Hs 90419 KIAA0882 protein 201
450983 AA305384 Hs 25740 ER01 (S cerevlslae) like 201
414825 X06370 Hs 77432 epidermal growth factor receptor (avlan 201
410701 AF198620 Hs 10283 RNA binding motif protein 8A 201
407317 AI204033 Hs 30792 ESTs, Weakly slmilarto I38022 hypothet 201
423551 AA327598 Hs 89633 ESTs 201
400810 NM.006560 Homo sapiens CUG triplet repea 200
407896 D76435 Hs 41154 Zic family member 1 (odd paired Drosophl 200
413129 AF292100 Hs 104613 RP42 homolog 200
427871 AW992405 Hs 59622 Homo sapiens, clone IMAGE 3507281, mRNA 200
444042 NM 004915 Hs 10237 ATP binding cassette, sub family G (WHIT 200
446770 AV660309 Hs 154986 ESTs, Weakly simllarto PLLP HUMAN PLASM 200
414390 BE281040 gb 601156234F1 NIH.MGC.21 Homo sapiens c 200
400074 Eos Control 200
451684 AF216751 Hs 26813 CDA14 200
451106 BE382701 Hs 25960 N MYC oncogene 200
419465 AW500239 Hs 21187 Homo sapiens cDNA FLJ23068 fis, clone L 200
409988 N27687 Hs 334334 transcriptoπ factor AP 2 alpha (actvat 200
458422 AI344782 DnaJ (Hsp40) homolog, subfamily C, embe 200
434636 AA083764 hypothetical protein MGC3178 200
442007 AA301116 Hs 142838 nucleolar phosphoproteln Nopp34 200
414569 AF109298 Hs 118258 prostate cancer associated protein 1 200 441991 AW844404 Hs 126901 Homo sapiens mRNA full length Insert cDN 200
410025 BE220489 Hs 113592 ESTs, Moderately similar to I54374 gene 200
436961 AW375974 Hs 156704 ESTs 200
411007 AA311529 Hs 67619 hypothetical protein My014 200
421808 AK000157 Hs 108502 hypothetical protein FLJ20150 200
450341 N90956 Hs 17230 hypothetical protein FLJ 22087 200
446565 D13757 Hs 311 phosphoribosyl pyrophosphate amidotransf 200
449636 AI656608 Hs 281328 ESTs, Weakly similar to T00378 KIAA0641 200
TABI F 11R
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT number Accession
429228 215430.1 BG676155 BM009591 AI479075 AI025794 A1017967 AA448270 BE466812 AA853422 AI392649 BG952034 AA513384 BF840124 BE714620
AW969605AI553633
451807 17758.2 BM479185 AL552795 AL577722 BF038888 BM127617 BF510346 AW450652 AA865478 AW449519 BM127314 AI806539 AW449522
AA993634AI827626 AA904788
421798 3042.4 BC017829 AW276646 AI984209 AA663933 AA634104 AA551528 AA634041 AA298038 BG483990 T89297 BF853958 H64685 T90329
T60644 T57747 BF852694 T92529 BG482852 BF883064 BF883066 N74880 AA829796 N90716
428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 AI928140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658
AA769094 BF446026 AW118719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704
AI356361 AI923640 AWO705O9 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311
AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 BI061872 BI059498 AA134476
AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166
400205 2538.1 NM.006265 D38551 X98294 BM477931 BM461566 AU123557 AU133303 AU134649 AW500421 BM172439 AW500587 AW503665
AW504355 AW503640 BM152454 AW505260 AI815984 AW504075 AW500716 AL597310 BC001229 BM474371 AA984202 AU135205
BE090841 AW163750 BF747730 BF898637 AI206506 AV660870 AV692110 AW386830 AV656831 N84710 AW993470 BF086802
BF758454 BG960772 BF757769 BI870853 BE018627 C75436 AW148744 BF757753 BG622067 BE909924 AA708208 BG530266 BF968015
AW992930 BF888862 BG536628 AA143164 AW748953 BG498922 BF885190 BF889005 BF754781 BF800003 BM476529 AI627668
AW028126 AL046011 BF590668 AI017447 AA579936 AI367597 AA699622 BE280597 AI124620 AI082548 AW274985 AA677870 AI056767
BE551689 AA287642 H94499 AI752427 AI652365 AW002374 AW062651 AA360834 N68B22 AU135442 AU125960 Z78334 BE545813
A1092115 BF312771 BF242859 BG533616 BG533761 BG164745 BG492433 BM473183 AA172043 AA172069 AU157092 AU151353
AU155318 BE302211 AI375022 AA085641 AU157923H88858 AA132730 AA115113 AA909781 AI475256 AA424206 AW572383 AW084296
AI184820 AI469178 AA782432 H92184 AA340562 BF195818 AA852821 AW576342 AA827107 AA173317 AW190014 AI918514 AA729372
AA729718 AI055958 AA331424 BE328601 AA515690 BI018896 AW628277 AA748368 AA626222 BG492636 AW380620 BF800058
AW370956 AA290909 R25857 BG952995 BF801437 AA172077 AU155890 AU149783 AI720904 AA902936 AA865727 AI470830 AV740677
AA142982 AA482485 AU145485 AW576399 AU156042 R63448 BF246427 BE928472 D25910 BF758439 BF968785 BE565238 AA355981
AI905607 BG291148 BG533096 BG532888 BF030886 BG613756 BE928471 BG574501 AA187596 AA361196 T95557 BG531446
BG527242 BG527513 BG611106 AA085995 BF847252 BG024608 BE540261 BG531236 AL579993 BG108733 BG483503 BG571032
BG492505
400291 1314911 1 AA927862 AA401369 AI873274
443695 20416.12 BE535598 AW204099 AW301249 AA609749 BF917914AA775742AV646137 AV646389AA314747
437834 294580.1 BG110129 AW749287 BE535498 AW749299 AW749293 AW749302 AW749298 AW749291 AW749294 AW749289 AW749288 AW749296
AA769294 AW749297 AW749295 AW749292 BE002573
433023 3970.8 BE999967 BF438599 AW864793 A1802B99 BE815132 AW468888 AI672189 AI052004 BF112024 AA772335 AW275054 AA573845
AI144148 AI968683 AA846676 AA927355 H80424 AW973295 R88209 F29868 BE928871
427365 1314911.1 AA927862 AA401369 AI873274
415989 10194.1 BC013389 BC017398 AI023543 AA191424 A1267700 AI469633 AW958465 AW953397 AA172056 BE940298 BF909208 BF909980
BF095153 BG285837 AI720344 BF541715 AA355086 AA172236
458098 23945.1 A1082245 BE467534 AI797130 BE467063 BE467767 BE218421 AI694996 BE327781 BE327407 BE833829 AA989054 AA459718 BE833855
BE550224 AA832519 AF086393 AV733386 BE465409 N29245 W07677 AA482971 BE503548 H18151 AA461301 W79223 W74510
AI090689 AL600773 AL600781 N46003 R28075 R34182 BE071550 AW885857 AI276145 AI276696 H97808 N20540 AI468553
412537 14066.1 AK025201 AA425472 A1694282 BG057305 AA907787 AI286170 AI684577 AJ420494 AI809865 BF058095 A1478773 AI160445 AL044114
AW665529 AI129239 AW297152 AI268215 AI469807 A1969353 BE552356 N66509 AA736741 AA382555 AW075811 AV759188 BI259364
BF445142 BG232065 A1141758 AI631202 AH 67566 AI208445 AA889823 BF982682 N90322 BI090882 BF208005 AW953918 AL044113
A1016793 AA382556AW235763 AA927051 AI862075 BE886691 BE619282
451752 10408.5 AB032997 AI141678 AW978722 BE467119 AI761408 BF727385 AW237035 A1934521 BF436248 A147966B Z40632 AA832081 AW295901
BF057835 BE465977 AI621269 BE465983 BF756369 N74056 A1817896 AA716567 AA934774 H62600 H09497 BF943762 BE395335
BE883333
444172 49300.2 BF526827 AA513594 AL515291 AV648373 AV648176 AA916789 BF002906 AW469960 BE466943 AI367749 AI559715 BF431260
AA937968 AI422252 AI288937 BF962778 AA909144 BF960004 BE671534 AI271719 BF925335 BE669504 BF433431 BF924838 A1218062
AW960577 AV722716 BI859067 BF944964 BE147740 BF938993
452279 11990.1 AF392454 AK023074 AI884890 AI814455 AW966220 BF736545 AA026021 AA286843 AA251918 BG197710 AA026294 AA337356
BC010422 AK023226 NM.022776 BM459496 AA769310 AI826460 AU153650 AU160375 AW166211 AW292992 BF433538 AI823888
AI684798 AI655985 AW770982 AI400454 AI276257 AA639510 AI689818 AW772604 AA807639 AU130298 AU132028 BF900889 BF904822
AY007102 AU143256 BG621460 AA829630 AI864665 AI084922 AA025234 AI360060 AA766554 AA026295 AA825817 AA251762
BE180751 BM464530 AV715833 AA779447 AI452519 AW418525 AA435643 D25894 AA435651 AA286844 N64369 AI702262 BG288063
BE170545 BM466232 BE299160 AA169573 AL567428 BF217285 BE967276
400277 170.1 Y00281 NM.002950 BC010839 BC007995 BG675232 BM468552 AL555484 BG831516 BF035300 BG677277 BF852972 BE314901
BF850656 AI371816 AA292474 AA375747 AA308414 BM454544 BI333370 BM049921 BI461428 BI465007 BI223401 BE856245 AW821164
BF914775 BF914761 AU125835 BI222678 B1091137 BF340536 BM462798 BI224452 BG707915 AL569160 AA443815 AW572867
AW363410 BF739268 BG010283 BI013120 BF818845 BF763468 AA305165 AI630370 AA039826 R24906 H02046 T96891 BF981330
AW936510 AA478169 H04587 BG166574 BI869342 BE562482 BE539637 AA165089 AL579118 AL553699 BE044054 AW117440 AI520674
BF435417 AW245648 AI952404 T29534 AU153459 AU152168 AW591591 AU146918 AI393187 AA478013 AU148143 AI224471 AI640728
AI871537 AW264752 N93787 AI189357 AV756134 AI471659 AU147466 AA779206 AU149419 AU149104 AU159135 AA312221 AW445119
AW021912 AI799771 F04407 AI285530 AI914643 AW068751 AA513325 AA164627 AA639285 AA569644 T96892 AI923594 BF439180
BI770936 BF032438 AU154884 AA682793 AW072992 AU158815 AI884444 AL048031 AU158922 AU152546 AI695187 AL048033 AI245650
AU148507 AW467451 BE536868 BF913001 BF062707 AL573082 AW067993 AA523354 BE886727 AI890705 AU159092 AI982693
AI817553 AA236729 AI687858 BG163767 AI524675 AI678155 AA127100 AI762661 AU159718 AI469720 AA483627 AW131696 R26868
AI199885 AW875614 AW938694 AW578974 BI763988 BG819168 BE874767 BG978292 BE162948 AL555483 AW189719 T56783 AI018819 AI476552 BI492837 AI824440 BG996262 AA932887 AI380726 R79530 AA622108 AI262575 T56782 R27437 BE784153 AW129549
AI675567 AI866759 BG987935
70312.1 AA151520 AI749635 AA149436 BE172702 AW317084 AA922501 AI302818 AI147563 AA789216 AI719336 AW612978 F34536 AI971386
AI246525 AI183312 R02554 AI360172 AA634282 AI022935 AA639461 AI086411 AI087086 AA633082 AI590029 AA856582 AW369734
AA150042 AA877171 AA456459 AI078529 R83333 AI161298 AA056987 AI350120 H88127 AA258759 AI673598 AA454566 AI342790
AI492606 AI159945 AI198009 AI198039 AI142751 AI141403 T81478 AW014110 AI197808 AI927796 AA534936 AA649735 AA649697
AI349452 AA719660 AW954285
418304 1093209.1 BE883520 BI057842 AA215702 AA215703 AA368006 BE006876 BE066555 438869 52134.1 AF075009 R63109 R63068 406685 0.0 M18728 443687 134710 H72674 BG925294 AA699932 BF061529 AI240821 AA676904 AI083582 AA766036 AA761066 AA761228 AV686983 AV646138 AV646121
AW961968 AA004250 AV658573 T08315 AA004669
453160 6028.5 BC009612 NM 003526 BI597616 AV761592 AV760377 AL601008 BI604131 BE645918 BG187760 BG181525 BG210634 BG192999
AI263307 AA344186 AW952966 AA033609 AA037562 AA722183 R79452 H70775 BF674991 BE769437 BG007856 AA037483 AW572535
AI143991 AA084581 AA033610 AV742510 AV735788 R08336
438118 1007899.1 AA778411 AW663081 AW753311 447349 1063443.1 BE743847 AW809603 BM469626 AI375546 438714 2576235.1 AA814859 AI582623 AA814857 454453 8582.4 BF313069 BE879305 AW752781 AW752727 AW752559 AW752578 AW752584 BF846118 AL545903 BF846115 AL525361 441128 20932.1 BC014072 BE328850 AI356567 AI148171 AI022165 BG149661 BF000671 AA233101 AA573721 AA447991 AW016855 AI005068 AA554071
BF478215 AA906902 AW014761 BE905651 BE512923 BM047129 AA243852 AA232991 AA127550 AA127551 AA570256 AI473237
BF033706 N90525 AW973623 AI359627 BG674574 BE903322
411605 10026.3 BG256892 H10532 N46614 R52610 AW977696 BM460488 W56819 BI042183 BG977498 BE767451 BF870009 BG477472 R61137 R14274
R20259 R09686 BI838226 BF034269 AA429173 BE741829 AW867495 AI123683 AW006831 BE831162 AW452753 AV742717 W86152
BF115102AI633815 BF921562 AA094230 BE092587 W86151 AA526153AI672156 BF914496 R12579 BF852352AA699780T57386
BF903022 09933AA678298
427521 513212.1 AW973352 BF222929 AW016853 BF059130 AI651829 BE551767 AA558414 AI339359 BF059601 AI961162 AI341422 AI206248 AI206165
AA548736 AA768578 AI539081 AW025957 AA736837 N79575 AW594357 AA480892 400247 2764.1 BC022339 BC009610 BC010537 X79805 NM.006713 U12979 BM467814 BM450743 AU132951 AU137129 BG493425 AV758819
BG708412 BG705885 BG702217 AV716638 BG777009 BI545689 BI552153 BM476712 BG770858 BG527656 BG528277 BG391388
AV716861 BI602926 BG290073 BI667399 BM451469 BI667173 BI602139 BG532171 BI669216 B1544727 BG721852 AV716503 AV701327
BM090738 BI492000 AI308856 BI544904 AL599813 AV715829 AV716505 AV714587 AV717902 BF668072 AV716385 BI461927 BM090954
AV717826 BG503676 AV647719 BG501392 BG428433 BE895629 BM313117 AW021050 BG435032 BM152910 AA313503 AA872377
BG574714 AV712054 AV732696 AA252476 AV712759 AL599643 BE790872 BG654930 W73337 AW675377 AV760376 AV725139
AV716379 AA887165 BE830003 AW023796 AL599291 A1902948 BG944042 F00781 AA352483 BG217897 N33888 AW581924 BG654730
D31410 AA353088 D31288 AA295029 H95170 BE935104 AU139980 BG772963 BG776470 BG532512 BG105449 BI545421 AV715456
AW386083 BG699714 AL535832 AL514940 BG190861 BG210593 AW999254 H95138 AA353863 BE764809 N50375 BE091363 BG701255
BI860846 BI832485 BG168150 BG028647 BE546301 BG900321 BI909737 BG702363 BG614141 BG611137 BG700121 BF031492 N85802
AV715940 N51590 BG993478 BE172016 AW893622
413413 26025.3 BG261240 BG231707 AI440201 BF540868 BF240794 BE779394 BG505096 AA129208 D82298 T10758 AU155599 BF857123 BF836348 429978 35194.2 BE738425 BE738323 BM126944 AW629678 AW265195 AI916735 A1394255 AI573090 AI354442 AW612857 AI339558 AI919424 AI377532
AI354441 AI308821 AA772275 AW055215 AI589705 AI336532 AA806547 AV682125 H93575 AW071172 AW769904 A1863985 AW265018
AW196655 D79662 BE042393 N75017 AW014741 C75509 BE748621 H92431 AW079261 AW901780 AA329482 AW960115 BI260621
AI767525 R31663 BI918664 AW963196 C06195 AI678018
410507 4450.2 AK027433 AF117064 NM.013319 BC004468 AI149901 AI150093 AI374696 AI566580 AA779898 BG696067 BG828923 BM051241
BM050350 AL580560 AL558826 BG182261 BG194259 BG194258 BF036155 AI026803 AI024570 AA702281 AI566953 AW662600
AA463546 F33147 AA357796 BE312357 AL516788 AW958856 BE730432 H85868 AA046292 BG478025 BG112231 BG763623 AA098922
BI093481 BE746381 AW962126 AI040821 BG026983 AA355288 BE392859 AA085571 BF875433 BF316280 BG740116 BG166624
441102 253699 AK054859 AA973905 AI299888 H63235 AA917019 AV722171 BE514107 BM051585 BE513744 BE295938 W32901 AA649212
439574 689966.1 BG532820 AW246001 AI469788 AI350090 AI446788 BE549330 W84862 AA837988
407242
450375 16559.3 BG570706 BG572749 AW606284 H04021 AA151166 AW954405 AA131254 BG056461 W46291 H01532 H04384 H03231 AA852876
H04410H59605 BE157601 AA113758
432908 452541.1 AF150424 AI861896 AA570057 AV738855 442643 2736.1 BC001588 BC007424 AF016369 NM.004697 B1756186 BE257019 BG500792 BI862776 AL121371 BG574833 AA703250 AA179511
AW052006 AI280150 AI914000 A1358319 AI081204 AI082594 AA992449 AI470821 AI655744 AW237529 AA678858 A1984430 BF433055
BE467594 BE467573 AA035630 AI289987 AI184802 AI681391 AW592416 AI138377 A1139266 AA961714 AI800163 AA418751 AW451928
AA668676 AI273444 AI494387 BE046912 AI276555 BF196021 AA700055 AA609305 AA772596 AI635758 AI635749 H95459 AW610290
BE464994 AA527136 BF374802 AI800175 AW195227 AI189676 BF802049 AL513632 AL554911 AL538845 BE297273 AA315321
BM451920 BE269268 BE292835 BE018128 BG755713 BM041095 BG677009 AL039691 BF995709 BE735586 BE296453 BG393609
BG824453 AL567522 AI745257 AW388641 AW301265 AI141144 AW029280 AU149362 AU152328 AA418960 AL121009 AI890398
AL528748 H13050 T47086 BI000575 BF334914 BF109661 R44450 H13259 T47087 AW388646 BF305834 AL577515 BM041600 BE889299
BF239768
419544 236329.1 BE787623 Al 909153 AW362351 AW362269 AW362245 AA526337 AA244193 BF876842 R79395 AI909154 455286 1149378.1 W27935 AW887403 AW887474 BE144384 BE144386 400240 27222.1 U04209 NM.005926AU121948 BI089933 BG425282 BG686931 AW821182 AU100079 BF700972AL565099 BG116731 BG200436
AL555789 AL047536 BF197395 BE504960 AI304957 AA932419 AW575886 AI916292 BI033772 BG995988 AL570315 BE348695 AA331214
AL514367 AA436797 AU134683 AL533163 BE818949 BE818946 BE818920 AU136916 AL047535 BG424079 BE294696 AU135607
BE207326 AL514368 AA318042 BF831066 BG106341 AW865170 BE937045 AI828674 BM083453 BE385535 AW865372 BF350485
AW382531 R01323AA092464
455290 1151240.1 U75810AW890252 449570 792531 AA001793 AA001871 448663 16112.4 BE966763 AA659765 AI961656 AI520918 AA761743 AA281477 N66431 BE463652 AA281329 AW272944 AA058687 BM145087 AA045516
AW341820 AA112515 AA258766 AI886639 AA714133 AA768245 AA035533 AI630459 T20165 AW971268 BE966269 AA522722
433009 2142268.1 AA761668 AA573621 R09670 R92814 447197 21768051 R36075 R36167 AI366546 432586 6633.1 BC022881 AU150944 BG750783 AW754175 AW857737 AI911659 AI050036 AA554053 AI826259 AA568548 449444 27351 U59185 NM.004696 AV734324 AI245349 AA369517 H88760 D79128 AA970406 H01059 H88761 H03446 BG620383 AU135008 AU136895
AU158158 AU155762 R73608 R65751 R23756 N74630 AW078687 BE439761 BE786351 R68994 BE785867 AW297502 AW297553
BG431545 AW814843 BF382644 BG429539 BE929862 BF811258
438578 2573130.1 AA811244 AI373188 AI240S09 441318 1989216.1 AA928233 AI078234 AI702558 H81727 442961 60316.2 BE966247 BE220885 BE467384 BE350135 BE672094 AI811582 AW665254 AA772731 AI283601 AA417067 AW197746 AI868357
AI792143 AA931120 AI758506 AA843761 BE737582 AW379586 N38812 BG567321 H13257
450251 40382.4 BE080483 AI689298 BE080416 422150 782.1 BI086421 BF059136 AW003898 BF446659 AI632891 AI628067 AI703179 AI961149 BF111022 AW614154 BE674215 AA687350 AA779426
BF591963 AW243344 AI356530 AI492508 AI694049 AI090422 AA465307 AI273387 BE674625 AW271971 AA969153 AW468593 AA984014
AI817491 AA970258 AI914450 AI018697 AW577591 AW577616 AA382101 AW954455 AI867266 AI707995 AI337384 BF208406 BF037100
BF223433 BF195517 BE673984 BF224124 BE813387 BG036579 BI553906 AA304995 AW361269 AW754160 AW361276 AW361271
AI867118 AW805555 AW361284 AW954458 AW958551 BG681507 H79011 AW205696 AW134957 AA747667 AW753296 BF939060
AW958549 BF910827 BG573750 BG168639
418330 36528.1 AK056357 BG704214 BG714527 BE409405 BE514455 BE408705 BM351826 BM049253 BM352137 AI659121 AW074357 AI674368
AW207841 BE646201 BM453984 BE674342 H19667 AI458175 AA279585 AW438632 AI687141 AA433999 AI245284 AA366782 AI948491
AW450917 AW450396 AI949813 BE217772 BE504863 AI628938 BF059575 AI564121 AI073854 AW510570 AI769861 AW235541
AW771224 AW236106 AW074675 AI919535 AA977064 AI364994 AI631614 W58249 AI034276 BE169956 AA743584 H19668 AI222131
AA883261 AI351534 F10472 AW466882 AA814964 W58250 BF036304 BF932025 BM474362 BG110744 AW964083 AW369992 F12868
BF842785 AA356665 BI091945 BG059147 W04844 R18398 BE925184 BI050068 BI825078 BE784883 AW175845 AA216130 BI257636
AA504328 AA713664 BF754840 AW235144 R38555 R42461 BG676504 T75135 R15365 BM012684
454645 1065291 AW811928 AW811887 AW811948 AW811847 455540 430605.1 AW993000 AV720038 AV720142 AW993293 BE080231 AW993284 424339 50559.1 NM 015720 AF219137 AL534420 AL524055 AL537346 AL538442 BG765888 AL530054 AL525377 BG474596 BG473144 BE251553
BG706099 AL538039 BG703131 BE255806 BF805256 F12128 AL566773 BI828686 BF761480 AI204971 BG818818 BI199246 AL534816
BF529941 AA324163 AL523285 BG914330 H07952 AL534815 BE769903 AI867802 BM310135 AL533702 BE254484 BF528852 BE867462
BE740130 AL134164 AL567115 AL533701 AL524054 AL515904 AL523284 AL568203 AL534419 BF981162 BE257148 AL561833
408839 234669.1 AI355222 BF378422 AA366587 BF874552 AW277084 R26970 D79194 R27662 414883 8371.2 AF274943 BG494894 AI719075 AA908783 AI935150 AI422691 AA910644 AA583187 BM272167 AI828996 AA527373 AW972459 AI831360
AA772418 AI033892 AA100926 AU154749 AI459432 AI423513 AI094597 AA740817 AI991988 AI090262 AI312104 BI256707 AA459522
AA416871 AI075239 AI339996 AA701623 AI139549 AI336880 AA633648 AI989380 AI362835 AA399239 AI146955 BF514270 N92892
AI348243 AI278887 AA459292 AI494230 BF507531 AI492600 AA962596 AW613002 AA293140 AA235549 BF108854 AA954344 N49682
AI457100 AW589407 AW300758 BE220715 BE220698 BE569091 BM009647 BF900351 AI537692 AI203723 AI857576 AA584410
AW371667 BM172363
453454 2736. BC001588 BC007424 AF016369 NM.004697 B1756186 BE257019 BG500792 BI862776 AL121371 BG574833 AA703250 AA179511
AW052006 AI280150 AI914000 AI358319 AI081204 AI082594 AA992449 AI470821 AI655744 AW237529 AA678858 AI984430 BF433055
BE467594 BE467573 AA035630 AI289987 AI184802 AI681391 AW592416 AI138377 AI139266 AA961714 AI800163 AA418751 AW451928
AA668676 AI273444 AI494387 BE046912 AI276555 BF196021 AA700055 AA609305 AA772596 AI635758 A1635749 H95459 AW610290
BE464994 AA527136 BF374802 AI800175 AW195227 AI189676 BF802049 AL513632 AL554911 AL538845 BE297273 AA315321
BM451920 BE269268 BE292835 BE018128 BG755713 BM041095 BG677009 AL039691 BF995709 BE735586 BE296453 BG393609
BG824453 AL567522 AI745257 AW388641 AW301265 AI141144 AW029280 AU149362 AU152328 AA418960 AL121009 AI890398
AL528748 H13050 T47086 BI000575 BF334914 BF109661 R44450 H13259 T47087 AW388646 BF305834 AL577515 BM041600 BE889299
BF239768
429588 1396089.1 AI092511 AI080271 AA455177 AI381859 AI381721
412452 71091.1 BE796667 BF330981 BE394193 Z45547 BG490525 F35734 AA130708 AA577072 AA446587 AA215665 AA978209 BG740729 BG746810
BE298184 AI356291 AI671975 AI818924 AV715722 AI078381 BI142391 AI201085 AI198283 AI077572 AI694848 AW016425 BM456416
AI277223 AW771476 F26140 AA102778 AW025780 R44726 AA761079 AI581346 AI991909 BM005939 BE537999 BG469717 AA114156
BF437200 BE774942
415889 12922.1 NM.052918 AF284756 BE019093 Z42986 BE328250 BE207835 R54516 R24563 H08127 BI522616 AA551620 H07879 AI174481 BF941262
BF222810 R54417 AW137766 AI638502 N22373 H08128 R44366 AW272405 AI675836 Z38786 N75618 F02463 AI654047 BI492031
AW021081
442092 227562 BM449821 BM069895 BM023170 AW025563 BG152606 BM023452 Al 862106 BG959957
459376 310101 BC002465 BE254864 BG472164 BE258770
410723 609025 AW070415 AA628250 AW204027 AI936167 AW054868 BF805308 AA100683 AA088786
429462 57612 BC008352 BM006782 AW245715 AI890356 BF445407 BE222242 AW139455 BE549685 AA987521 AA960934 AW245359 AA453285
AA976507 BG055359 BM007094
424399 2196. NM.058173 AF414087 W72837 BF742809 AW070916 BE092421 AI905687 AA340069 BE074512 AI905623 AI905633 BG202312 W72838
AI139456 BG218084 BE926938 BE186013 AW176044 AW291950 BG185269 BG197186 BG192597 BG183176 BG207535 AI127172
BE815819 AI905624 R75793 BG202313 AI905837 BE815853
440282 21425. NM.021188U90919 BM458077 BG214941 AL562127 BG197712 AW994207 AA043114 AW993474 AA631832 AI911529 BI001014
BE156322 BG319454 H27376 BG220618 BG189474 BG325006 AL519085 BM472894 AL520560 BG575806 AA319317 BG621802
BG912722 AV760869 AV760871 R13243 BE274097 BG327062 BI765172 BE614338 BG214923 B 153391 AU147675 N58119 AL043557
AL043558 AL043510 AA773474 AU148079 BF062869 AW189972 AW250398 AI028605 AI434688 AW149344 AI246783 AI961376 AI698209
AA251535 AU160747 AA579811 AI572570 AI656228 AA426093 AA127171 BF222487 AA725576 F21161 AI932217 BF222251 AI024660
AA780998 AI538862 AW140038 A1122909 AA493515 AA401920239789 F10942 F05081 AA814868 F10376 AA776314 AA993104 T94991
AW583990 AA128211 F03074 AL579261 AL519084 AA384895 BG196670 AW083526 BF220181 BE669988 BF907279 T23499 AL520559
AU149005 N38766 H96506 AA040865 AI263737 AA723350 AI168145 AA652386 AI374699 AA487377 AI927374 AI985531 AI352105
AI040092 AA486562 BM053020 Z41738 BE243710 AA601558 BM052743 AI445827 AA487260 AI982679 AW130546 AI743384 AI335647
AW978172 R40324 AV736436 BE966360 AI185467 AI367193 N75025 AW131068 BE940519 H43910 AA486659 BE614365 BF220261
BE181357 BG189473 BG210176 H 3958
412988 1342150.1 BE046680 BE046738 BE044958 435542 132718 1 AW975503 BE763276 H74234 AA687376 418647 243680 1 AA226513 AA383773 AA226198 424765 6857.1 AK021881 AU145974 AU145787 C16964 AA428211 AU119698 AA993264 BF999192 AW903017 AA346559 AU119446 AW581679
AA991677 AW898165 AW386878 AW890957 Z18340
439306 3941.3 BM013864 AI905414 AF086118 BE178507 AW161170 BE220199 BE221405 W01813 BG150053 N70760 N26062 H98499 AI290198
T80987 BE549149 BG106008 AW662681 AI590833 T71977
422405 17366.3 AW006867 AI373549 AA310278 400203 11774.1 NM.002794 D26599 BM469989 BF305151 BG821966 BI089030 AW007738 BI222910 BM049422 BG028749 AI189162 AI831230
AW131497 BM272215 BE791105 AW778828 AA479594 AA480133 AA131997 AA284572 AA453009 BF928258 AA152127 AA393918
BF765307 BE247542 BF934697 BF341798 BE253409 AA470620 AI828932 AW379902 AV762678 AV741784 AV760892 AI025755
AA878562 AA630630 AA761708 AA862518 AA865831 AA862947 N53065 AA131821 AA293499 N23342 N26856 AI147346 AW951549
AA772963 BE245986 BG208493 AI831666 BG474873 BI023168 AU149647 BG197069 BG191102 BF304178 BE536135 AA706900
AA443583 A1002710 AW276192 AU149842 BG214797 BG198193 AW197923 AW627799 T98663 BG194788 BG214656 BF345258
BG716363 AI066528 BI546220 AA393815 AA132004 AA353826 H97858 BG187823 BF841463 AI351714 AV735966 BG196439 BG216840
BG198438 BG400762
412700 18692.7 BG164322 BF510268 AI681542 BE222433 AI299965 BE220552 AA115728 BE896438
406740 00 AA577274 AA908437
442481 6787521 BG398943 N99828 AI110738 AF074645 BE969969 BE079873 BF185244
430677 117491 NM.001943 Z26317 BG750290 BM043721 AW361908 BG494570 AW996792 BF915903 AW753487 BI335109 BE018413 BE874074
BF333555 BI016581 BI014002 BI015917 BE731644 BE927177 BE697899 BF999996 BF929423 BG951608 AW858747 AW858755
AW858750 AW858749 AW858751 AW363742 D58979 BE003946 AW858999 BG951830 AW859003 BF738953 AW369461 AW363740
AW998641 BG978975 BG015802 AW991316 453331 16559.1 BG571303 AA410586 AA035018 BG572117 BG620022 AA147247 BG005785 BG014448 R31981 H02668 H12498 R36203 BF992089
R73999 T49904 R75732 BI057974 T53681 AA147933 N50695 R68588 R25671 R31935 R25110 R36105 AK055628 BE157467 AW663674
AA190993 H01642 BF510304 AA626915 AA746952 AI161014 AA099554 BG572534 AI803329 AI809932 AI808765 AA411449 AI378760
AA976929 AI378620 AA909684 R75632 AI360919 AI350463 AW069127 AA411621 AA742532 H12451 BE208298 H03612 H12839 N58781
R75957 BF996484 AI240665 BF989591 BI056086 BG001590 BF107035
409960 39576.1 BE644758 AI082238 BF940027 AI201079 AI436035 AW275966 AI085394 AI291655 AW070441 AI474134 AI268978 AI769279 AI567682
AA693941 BF477668 AW664149 AA283782 BF509538 AW296868 AI268977 AI168133 BM352065 AI262769 BF941976 AI056920
AA481861 BF763697 AL565888 BM352383 AA427768 AA385346 Al 186988 AA931831 AA134972 BF217480 BF111012 AA908246
AA319849 AA318136 AL514271 BF364291 AL515057 AV702312 AA377395 AL544217 AI34100O AW193583 AI350789 AA888338
BF945380 AW879092 AA130839 T91066 N92326 AI004389 AA078832 AL572370 W04622 BE314003 AW960808 BM360872 AA319160
AA130778AL514257
408673 13031.1 BG027435 BF746745 AF349017 NM.052963 AL553524 AL519055 AL525199 AL529016 BE208517 BI856042 BG480978 BE267120
AW815679 AL525198 AL561760 AA933030 AA634332 AA568280 AA927487 AW182340 AW592604 AW732157 AI680072 AI431328
AI357601 AI872335 AI032112 D25780 AL529015 AL576497 AA575842 BG223081 AA618007 BF310845 BF757605 BM012536 BI911537
BE964237
447128 11028.3 BG292064 AI452509 AI271898 BE048502 BI966153 X84721 AI858001 BM021943 AI553937 AI765259 F25787 AW015380 AA554539
AW059537 F35749 AA149853 AA961610 AI568815 AW973696 C00201 R77127 BG438065 AI244810 H00719
400249 993.1 BG260581 AI743827 AA182444 AA927609 NMJ01326 U15782 BC010533 AA779834 AI086366 AI452475 AW274511 BG056719
AW026350 AA808891 AW080007 AI763436 AU154714 AU155464 BF196839 AI934353 AI376072 BG232033 AI040445 AA700556
AW004704 BE047781 AA470756 AI091381 AI302228 AI400050 AI142702 AA614554 AI467907 AA282801 AI434140 AI357496 AA748501
AA430113 BF060907 AW207004 AI367341 AA873520 AA764823 AI077410 AA253061 AI052369 F08358 BM456285 B1518533 BI836074
AU133365 AU131081 AU127466 AA173834 AW999116 BG571523 AU100072 BG290403 AI743461 W90141 D58551 AA181551 AA094014
BG724183
439092 919640.1 AW978407 AA830149 M85983 AW503637 BF352096 407590 78212.1 BE293321 AA631602 AA281584 AA927393 AI831258 AA340072 BG009209 AW956385 AW838390 N94346 BF724763 AW082728
BE044419 AI417373 W69444 A1147614 AA632403 AI937606 AI864878 AI969211 AI081135 AA885000 AA926984 AA642586 AW079405
AA973001 AW628858 AI521070 BG912959 BI052498
424036 6226.1 NM 033445 BC001193 AI885781 BF794032 AA476620 AA810906 AA810905 AI291244 AI885097 AI359708 AI335629 H97396 AI344589
AA30U377 AA457566 AW771833 BE465621 AI364068 AI364452 AI648505 AI918342 AI928670 AA886580 AL531029 AA886344 AI186419
BG329096 BM045465 AL531028 BG437151 BE868021 AA179427
408756 MH1740.17 AA524743 BF515403 BM353526 AI803357 BF000688 AW665479 AI672715 AW150325 AW589318 AI693038 AI370572 AI167636
AA057236 AW439079 AI097376 AI382060 AI684871 AI684860 AA913419 AA806162 AI673426 BI324967 BM149631 BM145789 BM353796
AA913878 BM148707 N38884 BI761934 BM145978 BE243268 BE246569 N38883
449230 6182.6 BC006329 AK026224 BG105365 AI472084 AW074277 AI743908 BM309990 BI850432 AI094365 AI539568 AW779999 AI261365 AA988975
AI436272 AI559886 BI710742 AA988508 AA036678 AI867147 AW518513 AI620019 BE645777 AI801919 AW205320 AI457722 BF061996
BF061798 AA233854 AA232795 AA516294 AA830561 R74220 BG768337 AW392972 BE764979 BE257665
414390 2128.2 BC022204 AK027690 NM 032839 BI765386 BE903404 BG700172 BF701671 BG252600 W60255 AW301576 W01296 AV724003
BE999965 AI949788 BM040799 Z43693 BF082768 BF328302 H09192 BF332781 R34999 BG573394 N57281 BE009522 BE281040
458422 4340.3 NM.006260 BE048475 AW080036 AA287317 AA400028 AI204437 AI830642 AA644420 AW614662 AW261942 U28424 BG335330
AU148480 AI095508 BF727387 BG256497 AI521859 AW291686 AW007816 BG002833 AA853075 AA779079 BF082050 AI640393
AA522954 T55310 AW517649 AA127463 AA887984 AW206341 BE858004 AW772531 AA604169 H83777 BG290990 AI692188 AI223311
AI708839 D82262 AA600260 AI364786 AA471007
434636 15423.1 AJ420454 AF147430 AA910497 BF432963 AI701451 AI743089 AA429326 AI887812 AA315932 AI005464 AL043321 AI300993 AA425105
BE467230 BE669770 AA885637 BE503044 AW014324 AI809584 AW167510 AA921331 AA903224 W01644 AI762128 AA031404 BE550653
AI694045 BE043088 BE670430 AI630969 AI457315 BE644737 BE327316 AW295247 N92784 AI630807 BE328180 AI269949 AW245292
AA083765 AA256898 AI375535 AA430673 AI168735 AI589717 AA015942 AI693885 AW341205 AA931651 BF856764 BE468094 BF433393
BF445511 AA928976 AI817684 BF111008 AA428316 AA455858 N25716 AA568727 AI581817 AA427482 H40678 AA041483 N71630
H51826 BF969052 AA094470 AI560352 T98937 W52816 AA083764 TABLE 11C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers In this column are Genbank Identifier (GI) numbers 'Dunham I et al " refers to the publication entted ' The DNA sequence of human chromosome 22 " Dunham I et al , Nature (1999) 402489-495 Strand Indicates DNA strand from which exons were predicted
NLpositlon Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLpositlon
405770 2735037 Plus 61057-62075 404561 9795980 Minus 69039-70100 401451 6634068 Minus 119926-121272 401519 6649315 Plus 157315-157950 401866 8018106 Plus 73126-73623 403485 9966528 Plus 2888-3001,3198-3532,3655-4117 401464 6682291 Minus 170688-170834 404996 6007890 Plus 37999-38145,38652-38998,39727-39872,4055 402802 3287156 Minus 53242-53432 402408 9796239 Minus 110326-110491 401558 7139678 Plus 103510-104090 404632 9796668 Plus 45096-45229 404571 7249169 Minus 112450-112648 405558 1621110 Plus 4502-4644,5983-6083 406081 9123861 Minus 38115-38691 402496 9797769 Minus 8615-9103 403011 6693597 Minus 3468-3623 401203 9743387 Minus 172961-173056,173868-173928 404440 7528051 Plus 80430-81581 401435 8217934 Minus 54508-55233 406581 7711879 Minus 12694-12852 404607 7328770 Plus 28477-28591 401093 8516137 Minus 22335-23166 405366 2182280 Plus 22478-22632 404819 4678240 Plus 16223-16319,16427-16513,16736-16859,1694
9931121 Plus 29235-29336,36363-36580 401197 9719705 Plus 176341-176452
404580 6539738 Minus 240588-241589
402102 8117771 Minus 174566-174740
402812 6010110 Plus 25026-25091,25844-25920
402855 9662953 Minus 59763-59909
401405 7768126 Minus 69276-69452,69548-69958
404592 9943965 Minus 39067-39225
406203 7289992 Minus 82220-82639
404661 9797073 Plus 33374-33675,33769-34008
405411 3451356 Minus 17503-17778,18021-18290
400639 9887597 Plus 23150-23580
405705 4165009 Plus 120228-120800
403055 8748904 Minus 109532-110225
400884 9958187 Minus 57979-58189
404877 1519284 Plus 1095-2107
401160 6067118 Minus 8280-8945
403429 9719566 Minus 52789-52917
403154 7407986 Minus 14228-14736
401833 3063511 Minus 77974-78102,80090-80187,81695-81773,8717
402322 7630359 Minus 75078-75203
405204 7230116 Plus 126569-126754
403961 7596976 Minus 110393-110603
403969 8569909 Plus 31237-31375,32405-32506
401192 9719502 Minus 69559-70101
401832 3063511 Minus 53654-53793,57497-57647,60769-60981,6501
401797 6730720 Plus 6973-7118
404029 7671252 Plus 108716-111112
404831 6624702 Minus 16833-17020,20007-20120,21605-21799,2333
401463 6682291 Minus 163135-163262
403532 8076842 Minus 81750-81901
405264 7329374 Plus 28556-28684
400810 8567959 Minus 174204-174331,175062-175205
TABLE 1 A About 2867 genes upregulated In lunα and breast metastases to the brain relative to normal breast and lunα tissues
Pkey Unique Eos probeset Identifier number
ExAccn Exemplar Accession number, Genbank accession number
UniGenelD UniGene number
UniGene Title UniGene gene title
R1 90th percentile of breast and lung metastases to the brain Als divided by the 90th percentle of normal breast and lung Als, where the 15th percentile of all nomial body tissue Als was subtracted from the numerator and denominator
SEQ ID NO(s) SEQ ID number(s) for nucleic acid and protein sequences associated with table entry
Pkey ExAccn UniGenelD UniGene Title R1 SEQ ID NO(s)
406690 M29540 Hs 220529 carclnoembryonlc antgen related cell ad 4545 385
409103 AF251237 Hs 112208 XAGE 1 protein 2775 1389
412719 AW016610 Hs 816 ESTs 2770 18
417308 H60720 Hs 81892 KIAA0101 gene produd 21 61 25
419078 M93119 Hs 89584 Insulinoma associated 1 1940 2996
422963 M79141 Hs 13234 sphmgoslne 1 phosphate phosphohydrolase 1938 39
452838 U65011 Hs 30743 preferentially expressed antgen in mela 1585 79 121
428839 AI767756 Hs 82302 Homo sapiens cDNA FLJ14814 fis, clone NT 1575 52
433447 U29195 Hs 3281 neuronal pentraxln II 1570 60113
453857 AL080235 Hs 35861 Ras-lnduced senescence 1 (RIS1) 1519 81 122
425057 AA826434 Hs 1619 achaete scute complex (Drosophila) homol 1485
449722 BE280074 Hs 23960 cyclin B1 1455
426682 AV660038 Hs 2056 UDP glycosyltransferase 1 family, polype 1440
419875 AA853410 Hs 93557 proenkephalln 1402
455601 AI368680 Hs 816 SRY (sex determining region Y) box 2 1385
418738 AW388633 Hs 6682 solute earner family 7, (cationic ammo 1385
430130 AL137311 Hs 234074 Homo sapiens mRNA, cDNADKFZp761G02121 ( 1370
428342 AI739168 Homo sapiens cDNA FLJ13458 fis, clone PL 1370
422487 AJ010901 Hs 198267 mucin 4, tracheobronchial 1354
424001 W67883 Hs 137476 paternally expressed 10 1345
424922 BE386547 Hs 217112 hypothetical protein MGC10825 1325
412446 AI768015 ESTs 13 10
436217 T53925 Hs 107 fibnnogeπ like 1 1263
422440 NM 004812 Hs 116724 aldo keto reductase family 1, member B10 1260
412140 AA219691 Hs 73625 RAB6 interacting kinesin like (rabkines 1245
439897 NM 015310 Hs 6763 KIAA0942 protein 1236
427344 NM 000869 Hs 2142 5 hydroxytryptamine (serotonin) receptor 1225
435538 AB011540 Hs 4930 low density lipoproteln receptor-related 1200
425234 AW152225 Hs 165909 ESTs, Weakly slmilarto I38022 hypothet 1200
418329 AW247430 Hs 84152 cystathlonlne beta synthase 11 75
414219 W20010 Hs 75823 ALL1 fused gene from chromosome 1q 11 65
447329 BE090517 ESTs, Moderately similar to ALU8.HUMAN A 11 60
426514 BE616633 Hs 170195 bone morphogenetc protein 7 (osteogenic 11 55
413554 AA319146 Hs 75426 secretogranln II (chromogranin C) 11 40
414683 S78296 Hs 76888 hypothetical protein MGC12702 11 40
429922 Z97630 Hs 226117 H1 hlstone family, member 0 11 40
439926 AW014875 Hs 137007 ESTs 11 30
401451 NM.004496* Homo sapiens hepatocyte nude 11 30
436291 BE568452 Hs 344037 protein regulator of cytokinesis 1 11 30
442432 BE093589 Hs 38178 hypothetical protein FLJ23468 11 30
434001 AW950905 Hs 3697 aπgiotensinogen 11 21
432415 T16971 Hs 289014 ESTs, Weakly similar to A43932 mucin 2 p 1085
453439 AI572438 Hs 32976 guanine nucleotide binding protein 4 1073
410082 AA081594 Hs 158311 Musashi (Drosophila) homolog 1 1067
428450 NM 014791 Hs 184339 KIAA0175 gene product 1059
407137 T97307 gb ye53h05 s1 Soares fetal liver spleen 1055
457465 AW301344 Hs 122908 DNA replication factor 1025
457211 AW972565 Hs 32399 ESTs Weakly slmilarto S51797 vasodilat 1024
439963 AW247529 Hs 6793 platelet activating factor acetylhydrola 1022
422880 AF228704 Hs 193974 glutathlone reductase 10 15
422656 AI870435 Hs 1569 LIM homeobox protein 2 1015
409269 AA576953 Hs 22972 steroid 5 alpha reductase 2-lιke, H5AR g 1000
428931 AA994979 Hs 98967 ATPase, H() transporting, lysosomal non 985
446469 BE094848 Hs 15113 homogentsate 1,2-dloxygenase (homogenti 985
410442 X73424 Hs 63788 propionyl Coenzyme A carboxylase beta p 985
411305 BE241596 Hs 69547 myelln basic protein 984
407896 D76435 Hs 41154 Zlc family member 1 (odd paired Drosophl 975
446839 BE091926 Hs 16244 mitotc spindle coiled coll related prat 965
416602 NM 006159 Hs 79389 Protein kinase C-blndlng protein NELL2 945
432886 BE159028 Hs 279704 chromatn accessibility complex 1 930
453884 AA355925 Hs 36232 KIAA0186 gene product 930
407355 AA846203 Hs 193974 ESTs, Weakly simllarto ALU1 HUMAN ALU S 930
442547 AA306997 Hs 217484 ESTs, Weakly simllarto ALU1.HUMAN ALU S 925
443247 BE614387 Hs 333893 c-Myc target JP01 925
440274 R24595 Hs 7122 scraple responsive protein 1 923
409974 BE174106 Hs 225641 hypothetical protein FLJ13171 920
416655 AW968613 Hs 79428 BCL2/adenovlrus E1B 19kD Interacting pro 919
409041 AB033025 Hs 50081 Hypothetical protein, XP.051860 (KIAA119 915
456977 AK000252 Hs 169758 hypothetcal protein FLJ20245 913
410102 AW248508 Hs 279727 ESTs, homologue of PEM 3 [Ciona savlgnyi 909
437387 AI198874 Hs 28847 AD026 protein 908
411908 L27943 Hs 72924 cytdlne deamlnase 900 407168 R45175 Hs 117183 ESTs 890
433160 AW207002 Hs 134342 TASP for tests-specific adriamycln sens 888
446619 AU076643 Hs 313 secreted phosphoprotelπ 1 (osteopontln, 8 85
451807 W52854 hypothetical protein FLJ23293 slmilarto 875
452046 AB018345 Hs 27657 KIAA0802 protein 875
418836 AI655499 Hs 161712 BMP-R1B 871
416854 H40164 Hs 80296 Purkinje cell protein 4 8 65
454293 H49739 Hs 134013 ESTs, Moderately similar to HK61.HUMAN H 8 64
427528 AU077143 Hs 179565 mlnlchromosome maintenance deficient (S 863
431211 M86849 Hs 323733 gap Junction protein, beta 2, 26kD (conn 8 60
417576 AA339449 Hs 82285 phosphonbosylglycmamide formyltransfer 855
412519 AA196241 Hs 73980 troponlnTI, skeletal, slow 851
417333 AL157545 Hs 173179 bromodomain and PHD finger containing, 3 845
431726 NM 015361 Hs 268053 KIAA0029 protein 845
442355 AA456539 Hs 8262 lysosomal associated membrane protein 2 844
412482 AI499930 Hs 334885 mitochondnal GTP binding protein 840
429503 AA394183 Hs 204166 ESTs 840
429343 AK000785 Hs 199480 Homo sapiens, Slmilarto epsln 3, clone 839
427871 AW992405 Hs 59622 Homo sapiens, clone IMAGE 3507281, mRNA, 8 17
420234 AW404908 Hs 96038 Ric (Drosophila) like, expressed in many 8 15
447342 AI199268 Hs 19322 Homo sapiens, Simllarto RIKEN cDNA 2010 8 10
423472 AF041260 Hs 129057 breast carcinoma amplified sequence 1 8 08
414430 AI346201 Hs 76118 ublquitin carboxyl-termlnal esterase L1 805
443715 AI583187 Hs 9700 cyclin E1 805
447033 AI357412 Hs 157601 Predicted gene Eos cloned, secreted wΛ 805
407833 AW955632 Hs 66666 ESTs, Weakly slmilarto S19560 praline r 805
447343 AA256641 Hs 236894 ESTs, Highly similar to S02392 alpha 2 m 804
449349 AI825386 hypothetical protein FLJ21939 slmilarto 800
420039 NM 004605 Hs 94581 suifotraπsferase family, cytosolic, 2B, 797
429228 AI553633 hypothetical protein MGC33630 794
405770 NM.002362 Homo sapiens melanoma antigen, 785
411605 AW006831 ESTs 782
418203 X54942 Hs 83758 CDC28 protein kinase 2 780
442772 AW503680 Hs 5957 Homo sapiens clone 24416 mRNA sequence 780
444783 AK001468 Hs 62180 anillin (Drosophila Scraps homolog) act 775
431374 BE258532 Hs 251871 CTP synthase 770
414761 AU077228 Hs 77256 enhancer of zeste (Drosophila) homolog 2 770
451752 AB032997 KIAA1171 protein 770
443171 BE281128 Hs 9030 TONDU 768
444172 BE147740 ESTs, Moderately similar to I38022 hypot 765
445413 AA151342 Hs 12677 CGI-147 protein 765
440700 AW952281 Hs 296184 guanine nucleotide binding protein (G pr 765
407748 AL079409 Hs 38176 KIAA0606 protein, SCN Clrcadlan Oscillat 760
423242 AL039402 Hs 125783 DEME-6 protein 758
408633 AW963372 Hs 46677 PRO2000 protein 755
438461 AW075485 Hs 286049 phosphosenne amlnotransferase 755
424098 AF077374 Hs 139322 small praline πch protein 3 755
432467 T03667 Hs 239388 Human DNA sequence from clone RP1-304B14 754
427581 NM 014788 Hs 179703 KIAA0129 gene product 750
428648 AF052728 Hs 188021 potassium voltage-gated channel, subfami 750
425580 L11144 Hs 1907 galanin 740
400409 AF153341 Homo sapiens winged helix/forkhead trans 735
414706 AW340125 Hs 76989 KIAA0097 gene product 735
429276 AF056085 Hs 198612 G protein coupled receptor 51 725
449845 AW971183 Hs 6019 DnaJ (Hsp40) homolog, subfamily C, membe 723
410174 AA306007 Hs 59461 DKFZP434C245 protein 710
444670 H58373 Hs 332938 hypothetical protein MGC5370 710
418164 AI761820 Hs 41074 ESTs, Weakly slmilarto 139294 McLeod sy 705
429597 NM 003816 Hs 2442 a disintegnn and metalloprotelnase doma 700
429903 AL134197 Hs 93597 cyclln-dependeπt kinase 5, regulatory su 690
428966 AF059214 Hs 194687 cholesterol 25 hydroxylase 690
424834 AK001432 Hs 153408 Homo sapiens cDNA FLJ10570 fis, clone NT 690
430066 AI929659 Hs 237825 signal recognition particle 72kD 688
433212 BE218049 Hs 121820 ESTs 685
420309 AW043637 Hs 21766 ESTs, Weakly similar to ALU5 HUMAN ALU S I 685
409557 BE182896 Hs 3686 ESTs 685
430294 AI538226 Hs 32976 guanine nucleotide binding protein 4 683
415539 A1733881 Hs 72472 BMP-R1B (bone morphogenetc protein rec 680
400292 AA250737 Hs 72472 BMP-R1B (bone morphogenetc protein rec 675
449048 Z45051 Hs 22920 similar to S68401 (cattle) glucose indue 675
419743 AW408762 Hs 5957 Homo sapiens clone 24416 mRNA sequence 675
430937 X53463 Hs 2704 glutathione peroxidase 2 (gastrolntestln 675
442332 AI693251 Hs 8248 Target CAT 670
441020 W79283 Hs 35962 ESTs 666
428771 AB028992 Hs 193143 KIAA1069 protein 665
400205 NM.006265* Homo sapiens RAD21 (S pombe) 665
438321 AA576635 Hs 6153 CGI 48 protein 665
416208 AW291168 Hs 1295 ESTs, Weakly slmilarto MUC2.HUMAN MUCIN 665
421305 BE397354 Hs 324830 diptheria toxin resistance protein requl 665
448275 BE514434 Hs 20830 kinesin like 2 662
426283 NM 003937 Hs 169139 kynurenlnase (L-kynurenlne hydrolase) 661
452099 BE612992 Hs 27931 hypothetical protein FLJ10607 similar to 660
423134 AJ012582 Hs 124161 hyperpolaπzaton activated cyclic nucle 657
408524 D87942 Hs 46328 fucosyltransferase 2 (secretor status In 655
434094 AA305599 Hs 238205 hypothetical protein PRO2013 650
429183 AB014604 Hs 197955 KIAA0704 protein 650 426559 AB001914 Hs 170414 paired basic amino acid cleaving system 650
418327 U70370 Hs 84136 paired like homeodomaln transcπptlon fa 650
407999 AI126271 Hs 49433 ESTs, Weakly slmilarto YZ28 HUMAN HYPOT 648
458814 AI498957 Hs 170861 ESTs, Weakly similar to Z195.HUMAN ZINC 645
438209 AL120659 Hs 6111 aryl-hydrocarbon receptor nuclear transl 645
423634 AW959908 Hs 1690 hepaπn binding growth factor binding pr 645
430300 U60805 Hs 238648 oncostatln M receptor 640
426827 AW067805 Hs 172665 methylenetetrahydrofoiate dehydrogenase 639
401197 ENSP00000229263* HSPC213 639
408771 AW732573 Hs 47584 potassium voltage-gated channel, delayed 635
432731 R31178 Hs 287820 fibronectin 1 635
439979 AW600291 Hs 6823 hypothetical protein FLJ 10430 633
441362 BE614410 Hs 23044 RAD51 (S cerβvislae) homolog (E coli Re 631
413450 Z99716 Hs 75372 N acetylgaladosaminidase, alpha- 630
410762 AF226053 Hs 66170 HSKM B protein 630
434263 N34895 Hs 79187 ESTs 630
412715 NM 000947 Hs 74519 primase, polypeptde 2A (58kD) 629
433556 W56321 Hs 111460 calcium/calmodulin-dependent protein kin 625
419631 AW188117 popeye protein 3 625
407235 D20569 Hs 169407 SAC2 (suppressor of actin mutations 2, y 625
428484 AF104032 Hs 184601 solute camerfamlly 7 (catonlc ammo 623
408452 AA054683 Hs 192455 ESTs, Weakly slmilarto ALU7.HUMAN ALU S 622
412942 AL120344 Hs 75074 mitogen activated protein kinase actvat 621
447397 BE247676 Hs 18442 E-1 enzyme 620
400297 AI127076 Hs 306201 hypothetical protein DKFZp56401278 620
452259 AA317439 Hs 28707 signal sequence receptor, gamma (translo 620
446636 AC002563 Hs 15767 citron (rho interacting, seπne/threoπln 619
450800 BE395161 Hs 1390 proteasome (prosome macropain) subunlt 619
408527 AL135018 Hs 33074 Homo sapiens clone IMAGE 3606519, mRNA 6 17
416426 AA180256 Hs 210473 Homo sapiens cDNA FLJ14872 fis, clone PL 6 15
424544 M88700 Hs 150403 dopa decarboxylase (aromatic L amino acl 615
426471 M22440 Hs 170009 transforming growth fartor, alpha 615
428004 AA449563 Hs 151393 gluta ate cystelne ligase, catalytc sub 615
452240 AI591147 Hs 61232 ESTs 615
417933 X02308 Hs 82962 thymidylate synthetase 6 12
434826 AF155661 Hs 22265 pyruvate dehydrogenase phosphatase 611
423198 M81933 Hs 1634 cell division cycle 25A 610
416294 D86980 Hs 79170 KIAA0227 protein 610
429663 M68874 Hs 211587 phospholipase A2, group IVA (cytosolic, 608
407944 R34008 Hs 239727 desmocollin 2 608
422283 AW411307 Hs 114311 CDC45 (cell division cycle 45, S cerevis 607
451027 AW519204 Hs 40808 Homo sapiens, Similar to RIKEN cDNA 2810 606
401519 C15000476* gl|12737279|ref|XP_012163 1| 605
420281 AI623693 Hs 323494 Predicted cation efflux pump 605
408908 BE296227 Hs 250822 serine/threoπlne kinase 15 605
415138 C18356 Hs 295944 tissue factor pathway inhibitor 2 600
420153 N22120 Hs 75277 hypothetical protein FLJ13910 596
433437 U20536 Hs 3280 caspase 6, apoptosis related cystelne pr 596
408045 AW138959 Hs 245123 ESTs 595
433675 AW977653 Hs 75319 πbonucleotide reductase M2 polypeptide 595
446595 T57448 Hs 15467 hypothetical protein FLJ20725 595
408298 AI745325 Hs 271923 Homo sapiens cDNA FLJ22785 fis clone K 595
417454 NM 000202 Hs 172458 Iduronate 2 sulfatase (Hunter syndrome) 594
425071 NM 013989 Hs 154424 deiodlnase, iodotiyronme, type II 591
416933 BE561850 Hs 80506 small nuclear πbonucleoprotein polypept 590
457579 AB030816 Hs 36761 HRAS like suppressor 590
428987 NM.004751 Hs 194710 glucosamlnyl (N-acetyl) traπsferase 3, m 590
406399 NM.003122* Homo sapiens seπne protease 590
442739 NM 007274 Hs 8679 cytosolic acyl coenzyme A thloester hydr 587
420344 BE463721 Hs 97101 putative G protein coupled receptor 585
452092 BE245374 Hs 27842 hypothetical protein FLJ11210 585
429925 NM 000786 Hs 226213 cytochrome P450, 51 (lanosterol 14 alpha 585
453204 R10799 Hs 191990 ESTs 585
433345 AI681545 Hs 152982 hypothetical protein FLJ13117 585
431548 AI834273 Hs 9711 novel protein 585
429966 BE081342 Hs 283037 HSPC039 protein 580
414341 D80004 Hs 75909 KIAA0182 protein 580
449145 AI632122 Hs 198408 ESTs 580
447334 AA515032 Hs 91109 ESTs 580
423453 AW450737 Hs 128791 CGI 09 protein 580
410619 BE512730 Hs 65114 keratin 18 574
416990 AF124145 Hs 80731 autocrine motllty factor receptor 573
430454 AW469011 Hs 105635 ESTs 572
430569 AF241254 Hs 178098 anglotensin I converting enzyme (peptdy 572
419926 AW900992 Hs 93796 DKFZP586D2223 protein 570
443180 R15875 Hs 258576 claudln 12 570
428832 AA578229 Hs 324239 ESTs, Moderately similar to ZN91.HUMAN Z 570
433001 AF217513 Hs 279905 clone HQ0310 PRO0310p1 567
425397 J04088 Hs 156346 topolsomerase (DNA) II alpha (170kD) 567
443426 AF098158 Hs 9329 chromosome 20 open reading frame 1 565
409619 AK001015 Hs 55220 BCL2 associated athanogene 2 565
416815 U41514 Hs 80120 UDP N acetyl-alpha D-galactosamlne polyp 565
407378 AA299264 Hs 57776 ESTs, Moderately similar to I38022 hypot 565
427658 H61387 Hs 30868 nogo receptor 565
445903 AI347487 Hs 132781 class I cytokine receptor 565
401866 Target Exon 565 439680 AW245741 Hs 58461 ESTs, Weakly slmilarto A35659 krueppel 565
415752 BE314524 Hs 78776 putative transmembrane protein 564
440351 AF030933 Hs 7179 RAD1 (S pombe) homolog 560
434834 AF156774 Hs 324020 1 acylglycerol 3 phosphate 0 acyltransfe 560
452461 N78223 Hs 108106 transcπpton factor 560
424140 Z48051 Hs 141308 myelin ollgodendrocyte glycoprotein 560
409439 AW390511 Hs 288862 Homo sapiens cDNA FLJ21260 fis, clone C 559
442315 AA173992 Hs 7956 ESTs, Moderately similar to ZN91 HUMAN Z 558
437389 AL359587 Hs 271586 hypothetical protein DKFZp762M115 555
400277 Eos Control 552
442313 BE388898 Hs 8215 hypothetical protein FLJ11307 550
449444 AW818436 solute earner family 16 (monocarboxylic 550
420734 AW972872 Hs 293736 ESTs 550
422756 AA441787 Hs 119689 glycoprotein hormones, alpha polypeptde 545
442961 BE614474 F box only protein 22 545
439580 AF086401 Hs 293847 ESTs, Moderately similar to S65657 alpha 545
439772 AL365406 Hs 10268 Homo sapiens mRNA full length Insert cDN 545
443695 AW204099 ESTs, Weakly simllarto AF1267801 retln 545
409757 NM 001898 Hs 123114 cystatn SN 543
422150 AI867118 calpastatn 542
450325 AI935962 Hs 91973 ESTs 541
444758 AL044878 Hs 11899 3 hydroxy-3 methylglutaryl Coenzyme A re 540
445266 BE222118 Hs 12479 associated molecule with the SH3 domain 540
457001 J03258 Hs 2062 vitamin D (1,25- dihydroxyvitamlπ D3) re 540
422938 NM 001809 Hs 1594 centromere protein A (17kD) 540
446342 BE298665 Hs 14846 solute earner family 7 (catonlo amino 540
425994 AK000207 Hs 165803 hypothetical protein FLJ20200 537
409799 D11928 Hs 76845 phosphosenne phosphatase like 535
437834 AA769294 gb nz36g03 s1 NCI.CGAP.GCBI Homo sapiens 535
407244 M10014 fibπnogen, gamma polypeptide 535
437762 T78028 Hs 154679 synaptotagmln 1 533
441633 AW958544 Hs 112242 normal mucosa of esophagus specific ! 532
452223 AA425467 Hs 8035 hypothetical protein MGC2827 531
450256 AA286887 Hs 24724 MFH amplified sequences with leuclne πc 531
430335 D80007 Hs 239499 KIAA0185 protein 530
430287 AW182459 Hs 125759 ESTs, Weakly similar to LEU5.HUMAN LEUKE 530
433485 AI493076 Hs 306098 aldo keto reductase family 1, member C2 530
423739 AA398155 Hs 97600 ESTs 530
458621 AI221741 Hs 117777 ESTs 530
413585 Al 133452 Hs 75431 fibπnogen, gamma polypeptide 530
427719 AI393122 Hs 134726 ESTs 529
452721 AJ269529 Hs 301871 solute carnerfamily 37 (glycerol 3 pho 527
445139 AB037848 Hs 12365 synaptotagmln XIII 527
422095 AI868872 Hs 282804 hypothetical protein FLJ22704 526
438915 AA280174 Hs 285681 Williams Beuren syndrome chromosome regi 525
425322 U63630 Hs 155637 protein kinase, DNA activated, catalytic 524
437915 AI637993 Hs 202312 Homo sapiens clone N11 NTera2D1 teratoca 520
444735 BE019923 Hs 243122 hypothetical protein FLJ13057 simllarto 520
439574 AI469788 ESTs 520
408411 C15118 Hs 322482 hypothetical protein DKFZp566J2046 520
421077 AK000061 Hs 101590 hypothetical protein 520
437659 AB007944 Hs 5737 KIAA0475 gene product 515
433023 AW864793 thrombospondln 1 515
417059 AL037672 Hs 81071 extracellular matπx protein 1 5 14
434061 AW024973 Hs 283675 NPD009 protein 5 12
431448 AL137517 Hs 306201 hypothetical protein DKFZp56401278 510
404568 NM 022071* Homo sapiens hypothetical pro 5 10
420942 H03514 Hs 15589 ESTs 510
410340 AW182833 Hs 112188 hypothetical protein FLJ13149 510
441031 AI110684 Hs 7645 flbnnogen, B beta polypeptide 510
433862 D86960 Hs 3610 KIAA0205 gene product 510
439108 AW163034 Hs 6467 synaptogynn 3 507
435664 AI032087 Hs 269819 ESTs 505
422486 BE514492 Hs 117487 gene near HD on 4p163 with homology to 505
431789 H19500 Hs 269222 mltogen activated protein kinase 4 505
424905 NM 002497 Hs 153704 NIMA (never in mitosis gene a)-related k 505
442053 R35343 Hs 24968 Human DNA sequence from clone RP1-233G16 505
415691 AW963979 Hs 24723 ESTs 500
408705 AA312135 Hs 46967 HSPC034 protein 500
424179 F30712 Hs 334573 Homo sapiens, clone IMAGE 4285740, mRNA 500
426318 AA375125 Hs 147112 Homo sapiens cDNA FLJ22322 fis, clone H 500
427675 AW138190 Hs 180248 zinc linger protein 124 (HZF 16) 500
407198 H91679 gb yv04a07 s1 Soares fetal liver spleen 500
412935 BE267045 Hs 75064 tubulln specific chaperone c 497
432378 AI493046 Hs 146133 ESTs 495
428728 NM 016625 Hs 191381 hypothetical protein 495
416111 AA033813 Hs 79018 chromatn assembly factor 1, subunlt A ( 495
441224 AU076964 Hs 7753 calumenin 495
415339 NM 015156 Hs 78398 KIAA0071 protein 495
450353 AI244661 Hs 103296 ESTs, Weakly slmilarto S65657 alpha-1C- 495
441377 BE218239 Hs 202656 ESTs 495
422765 AW409701 Hs 1578 baculoviral IAP repeat containing 5 (sur 495
431566 AF176012 Hs 260720 J domain containing protein 1 494
429788 U87791 Hs 221040 HBS1 (S cerevlslae) like 494
404561 trichorhiπophalaπgeal syndrome I gene (T 493
437739 AW579216 Hs 264610 ESTs, Moderately similar to Ibd1 [H sapi 493 438549 BE386801 Hs 21858 tπnucleotde repeat containing 3 492
424308 AW975531 Hs 154443 mlnlchromosome maintenance deficient (S 491
403485 C3001813* gi|12737279|ref|XP_0121631| k 490
433929 AI375499 Hs 27379 ESTs 490
416000 R82342 Hs 79856 ESTs, Weakly slmilarto S65657 alpha-1C- 490
424381 AA285249 Hs 146329 protein kinase Chk2 (CHEK2) 490
409420 Z15008 Hs 54451 lamlnln, gamma 2 (nicein (100kD), kallπl 489
426006 R49031 Hs 22627 ESTs 486
447349 AI375546 gb tc23d04 x1 Soaresjotal_fetus_Nb2HF8_ 486
415786 AW419196 Hs 257924 hypothetical protein FLJ13782 485
450149 AW969781 Hs 132863 Zic family member 2 (odd paired Drosophi 4 85
423551 AA327598 Hs 89633 ESTs 4 83
417348 AI940507 Hs 318526 hypothetical protein FLJ12661 481
422616 BE300330 Hs 118725 selenophosphate synthetase 2 480
427209 H06509 Hs 92423 KIAA1566 protein 480
423554 M90516 Hs 1674 glutamine fructose-6 phosphate transamln 480
419586 AI088485 Hs 144759 ESTs, Weakly slmilarto I38022 hypothet 480
437435 AA249439 Hs 27027 hypothetical protein DKFZp762H1311 480
424602 AK002055 Hs 151046 hypothetical protein FLJ11193 480
442760 BE075297 Hs 6614 ESTs, Weakly similar to A43932 mucin 2 p 480
458098 BE550224 metallothloneln 1E (functional) 480
418322 AA284166 Hs 84113 cyclin-dependent kinase Inhibitor 3 (CDK 477
420956 AA351584 Hs 100543 Homo sapiens clone 24505 mRNA sequence 476
408296 AL117452 Hs 44155 DKFZP586G1517 protein 475
414343 AL036166 Hs 75914 coated vesicle membrane protein 475
438613 C05569 Hs 243122 hypothetical protein FLJ13057 simllarto 475
458809 AW972512 Hs 20985 sιn3 associated polypeptide, 30kD 475
430935 AW072916 zinc finger protein 131 (clone pHZ-10) 475
441285 NM.002374 Hs 167 microtubule associated protein 2 475
433201 AB040896 Hs 21104 KIAA1463 protein 475
441553 AA281219 Hs 121296 ESTs 474
402812 NM.004930* Homo sapiens capping protein 473
434203 BE262677 Hs 283558 hypothetical protein PR01855 472
431899 AA521381 Hs 187726 ESTs 471
401464 hlstone deacetylase 5 470
413431 AW246428 Hs 75355 ublquitin conjugating enzyme E2N (homolo 470
453496 AA442103 Hs 33084 solute earner family 2 (facilitated glu 470
447276 AL049795 Hs 17987 hypothetical protein MGC1203 470
415927 AL120168 Hs 78919 Kell blood group precursor (McLeod pheno 470
418250 U29926 Hs 83918 adenoslne monophosphate deammase (isofo 470
428654 NM 012091 Hs 188661 adenosiπe deamlnase, tRNA specific 1 470
412537 AL031778 nuclear tranεcπption factor Y, alpha 470
421898 AA259011 Hs 109268 hypothetical protein FLJ12552 470
425523 AB007948 Hs 158244 KIAA0479 protein 470
451061 AW291487 Hs 213659 ESTs Weakly slmilarto KIAA1357 protein 470
424378 W28020 Hs 167988 neural cell adhesion molecule 1 468
426997 BE620738 Hs 173125 peptidylprolyl Isomerase F (cyclophilm 467
441024 AW081530 Hs 268231 ESTs 465
424085 NM 002914 Hs 139226 replication factor C (activator 1) 2 (40 465
432840 AK001403 Hs 279521 hypothetical protein FLJ20530 465
428829 R14050 Hs 194051 Homo sapiens mRNA cDNA DKFZp566B213 (fr 465
438898 AI819863 Hs 106243 ESTs 465
426784 U03749 Hs 172216 chromogranln A (parathyroid secretory pr 465
435937 AA830893 Hs 119769 ESTs 465
419551 AW582256 Hs 91011 anteπor gradient 2 (Xeπepus laevis) hom 463
431512 BE270734 Hs 2795 lactate dehydrogenase A 462
452834 AI638627 Hs 105685 KIAA1688 protein 460
444858 AI199738 Hs 208275 ESTs, Weakly slmilarto ALUA HUMAN llll 460
447519 U46258 Hs 339665 ESTs 460
408089 H59799 Hs 42644 thloredoxln like 460
413597 AW302885 Hs 117183 ESTs 460
449543 AF070632 Hs 23729 Homo sapiens clone 24405 mRNA sequence 460
418803 U50079 Hs 88556 hlstone deacetylase 1 459
408363 NM 003389 Hs 44396 coronln actln-binding protein, 2A 458
432441 AW292425 Hs 163484 Intron of hepatocyte nuclear factor 3 al 455
414770 BE257224 Homo sapiens, clone IMAGE 3873720 mRNA 455
433561 BE540937 Hs 20104 hypothetical protein FLJ00052 455
412970 AB026436 Hs 177534 dual specificity phosphatase 10 455
421928 AF013758 Hs 109643 polyadenylate binding protein Interactn 455
413476 U25849 Hs 75393 add phosphatase 1, soluble 454
426158 NM.001982 Hs 199067 v erb b2 avlan erythroblastc leukemia v 453
406181 Target Exon 452
449644 AW960707 Hs 148324 ESTs 452
438714 AA814859 ESTs 450
438880 AF075022 Hs 101480 ESTs 450
431452 AI073641 Hs 152372 ESTs, Weakly slmilarto 2109260A B cell 450
442108 AW452649 Hs 166314 ESTs 450
416072 AL110370 Hs 79000 growth associated protein 43 449
414320 U13616 Hs 75893 ankynn 3, node of Ranvler (ankyππ G) 449
446572 AV659151 Hs 282961 ESTs 448
420005 AW271106 Hs 133294 ESTs 447
423979 AF229181 Hs 136644 CS box containing WD protein 445
425849 AJ000512 Hs 296323 serum/glucocorticoid regulated kinase 445
443257 AI334040 Hs 11614 HSPC065 protein 445
421227 R78581 Hs 266308 mosaic serine protease 445
432339 AW411259 ESTs 445 426699 AA383337 Hs 121269 ESTs 445
418661 NM 001949 HS 1189 E2F transcription factor 3 445
439609 AW971945 Hs 293236 ESTs 445
438869 AFO750O9 gb Homo sapiens full length insert cDNA 445
424163 NM 007071 Hs 142245 HERV-H LTR associating 3 443
452459 AI356895 Hs 49359 hypothetcal protein DKFZp547E052 443
408548 AA055449 Hs 63187 ESTs, Weakly similar to ALUC.HUMAN llll 440
419594 AA013051 Hs 91417 topolsomerase (DNA) II binding protein 440
431912 AI660552 ESTs, Weakly similar to A56154 Abl subst 440
407930 AA045847 Hs 188361 Homo sapiens cDNA FLJ12807 fis, clone NT 440
416902 AA375634 Hs 288974 hypothetical protein FLJ12528 440
423673 BE003054 Hs 1695 matrix metalloprotelnase 12 (macrophage 440
429687 AI675749 Hs 211608 nucleoporin 153kD 440
404996 Target Exon 440
415156 X84908 Hs 78060 phosphorylase kinase, beta 439
445871 AI702901 Hs 145582 ESTs, Weakly similar to FOR4 MOUSE FORMI 438
420522 AW957137 Hs 98541 hypothetical protein 438
418816 T29621 Hs 88778 carbonyl reductase 1 437
457650 AA649162 Hs 236456 ESTs 436
422809 AK001379 Hs 121028 hypothetical protein FLJ10549 435
421437 AW821252 Hs 104336 hypothetical protein 435
450251 BE080483 gb QV1 BT0630 280200 086 a05 BT0630 Homo 435
436869 NM.014867 Hs 5333 KIAA0711 gene product 435
448552 AW973653 Hs 20104 hypothetical protein FLJ00052 435
427083 NM.006363 Hs 173497 Sec23 (S cerevisiae) homolog B 432
445160 AI299144 Hs 101937 sine oculis homeobox (Drosophila) homolo 432
423681 AB023215 Hs 131525 Homo sapiens mRNA cDNA DKFZp434E199 (fr 431
412452 AA215731 suppression of tumongeπicity 5 431
433020 AI375726 Hs 279918 hypothetical protein 430
434815 AF155582 Hs 46744 corel UDP-galactose N acetylgalactosamln 430
402802 NM.001397 Homo sapiens endothelln conver 430
402408 NM_030920*Homo sapiens hypothetical pro 430
445867 AF272663 Hs 13405 gephyπn 430
448920 AW408009 Hs 225B0 alkylglycerone phosphate synthase 430
446006 NM 004403 Hs 13530 deafness, autosomal dominant 5 428
430589 AJ002744 Hs 246315 UDP N acetyl alpha D-galactosamlne polyp 427
407807 AL031427 Hs 40094 Human DNA sequence from clone 167A19 on 427
417615 BE548641 Hs 82314 hypoxanthine phosphoπbosyltransferase 1 427
425843 BE313280 Hs 159627 death associated protein 3 426
443837 AI984625 Hs 9884 spindle pole body protein 426
425387 AB037864 Hs 156051 KIAA1443 protein 426
432978 AF126743 Hs 279884 DNAJ domain containing 426
431797 BE169641 Hs 270134 hypothetical protein FLJ20280 426
410366 AI267589 Hs 302689 hypothetical protein 426
432350 NM 005865 Hs 274407 protease seπne, 16 (thymus) 425
433002 AF048730 Hs 279906 cyclin T1 425
422168 AA586894 Hs 112408 S100 calcium binding protein A7 (psoπas 425
453005 AW055308 Hs 31803 ESTs, Weakly similar to N WASP [H sapien 423
421875 AA299607 Hs 98969 ESTs 421
432140 AK000404 Hs 272688 hypothetical protein FLJ20397 420
402053 C11001722*gι|11436283|ref|XP_0069591| 420
440426 AI159800 Hs 7181 Homo sapiens cDNA FLJ13663 fis, clone PL 420
428479 Y00272 Hs 334562 cell division cycle 2, G1 to S and G2 to 420
418259 AA215404 ESTs 420
413582 AW295647 Hs 71331 hypothetical protein MGC5350 420
436679 AI127483 Hs 120451 ESTs, Weakly simllarto unnamed protein 420
446880 AI811807 Hs 108646 Homo sapiens cDNA FLJ14934 fis, clone PL 419
449976 H06350 Hs 135056 Human DNA sequence from clone RP5 850E9 19
433409 AI278802 Hs 25661 ESTs 419
451380 H09280 Hs 13234 ESTs 416
434540 NM 016045 Hs 3945 CGI-107 protein 416
456844 AI264155 Hs 152981 CDP diacylglycerol synthase (phosphatlda 416
409445 AW341217 Hs 14139 ESTs, Weakly similar to JC5314 CDC28/cdc 415
448999 AF179274 Hs 22791 transmembrane protein with EGF like and 415
452110 T47667 Hs 28005 Homo sapiens cDNA FLJ 11309 fis, clone PL 415
437682 AA476652 Hs 94952 Homo sapiens cDNA FLJ23371 fis, clone H 415
437250 BE257342 Hs 94576 hypothetical protein MGC3062 415
452279 AA286844 hypothetical protein FLJ13164 415
425242 D13635 Hs 155287 KIAA0010 gene product 415
433388 AI432672 Hs 288539 hypothetical protein FLJ22191 415
448072 AI459306 Hs 24908 ESTs 415
423073 BE252922 Hs 123119 MAD (mothers against decapentapleglc, Dr 415
444371 BE540274 Hs 239 forkhead boxMI 14
453951 AI676235 Hs 32163 ESTs 410
422576 BE548555 Hs 118554 CGI 83 protein 410
401558 ENSP00000220478' SECRETOGRANIN 111 410
414962 AF273304 Hs 235376 XPMC2 protein 410
431585 BE242803 Hs 262823 hypothetical protein FLJ10326 410
455505 AW970640 Hs 309071 ESTs 410
449230 BE613348 melanoma cell adhesion molecule 409
434474 AL042936 Hs 211571 holocytochrome c synthase (cytochrome c 408
453902 BE502341 Hs 3402 ESTs 408
430387 AW372884 Hs 240770 nuclear cap binding protein subunlt 2, 2 408
431183 NM.006855 Hs 250696 KDEL (Lys Asp Glu Leu) endoplasmlc retlc 407
424130 AL050136 Hs 140945 Homo sapiens mRNA, cDNA DKFZp586L141 (fr 407
433029 NM 014322 Hs 279926 opsin 3 (encephalopsln) 406 443683 BE241717 Hs 9676 uncharactenzed hypothalamus protein HTO 406
415701 NM 003878 Hs 78619 gamma-glutamyl hydrolase (conjugase, fol 406
412205 N33818 Hs 20274 ESTs, Weakly similar to unnamed protein 405
450193 AI916071 Hs 15607 Homo sapiens Fanconi anemia complementat 405
422072 AB018255 Hs 111138 KIAA0712 gene product 405
433077 AA314262 Hs 289008 YDD19 protein 405
413333 M74028 Hs 75297 fibroblast growth factor 1 (acidic) 405
417720 AA205625 Hs 208067 ESTs 404
456508 AA502764 Hs 123469 ESTs, Weakly simllarto AF2088551 BM 01 403
437967 BE277414 Hs 5947 mel transforming oπcogene (deπved from 403
428471 X57348 Hs 184510 stratifin 402
409518 BE384836 Hs 3454 KIAA1821 protein 402
451468 AW503398 Hs 293663 ESTs, Moderately similar to I38022 hypot 400
421977 W94197 Hs 110165 rtbosomal protein L26 homolog 400
413413 D82520 zlno finger protein 36 (KOX 18) 400
420851 AA281062 Hs 29493 hypothetical protein FLJ20142 400
446873 AI554439 ESTs 400
402496 Target Exon 398
408784 AW971350 Hs 63386 ESTs 397
418004 U37519 Hs 87539 aldehyde dehydrogenase 3 family, member 396
447514 AI809314 Hs 208501 ESTs, Weakly similar to B34087 hypotheti 396
430178 AW449612 Hs 152475 3'UTR of achaete scute complex (Drosoph 396
449810 AB008681 Hs 23994 activin A receptor, type IIB 396
422309 U79745 Hs 114924 solute earner family 16 (monocarboxylic 396
437763 AA469369 Hs 5831 tissue Inhibitor of metalloprotelnase 1 396
430791 AA486293 Hs 272068 ESTs, Weakly simllarto ALU3.HUMAN ALU S 396
408761 AA057264 Hs 238936 ESTs Weakly similar to (defline notava 395
419713 AW968058 Hs 92381 nudix (nucleoside dlphosphate linked mol 395
426227 U67058 Hs 154299 Human proteinase activated receptor-2 R 395
448595 AB014544 Hs 21572 KIAA0644 gene product 395
423175 W27595 Hs 347310 hypothetical protein FLJ14627 395
425649 U30930 Hs 158540 UDP glycosyltransferase 8 (UDP-galactose 395
411678 AI907114 Hs 71465 squalene epoxidase 394
435854 AJ278120 Hs 4996 putative ankyrin repeat containing prate 393
424954 NM 000546 Hs 1846 tumor protein p53 (Li Fraumem syndrome) 392
442767 AI017208 Hs 131149 ESTs 392
407634 AW016569 Hs 136414 UDP-GlcNAc betaGal beta 1,3 N acetylgluc 391
457819 AA057484 Hs 35406 FLJ20522 Hypothetcal protein FLJ20522 391
410418 D31382 Hs 63325 transmembrane protease, seπne 4 390
404704 NM.001539* Homo sapiens heat shock prate 390
403127 polymerase (DNA directed), delta 1, cata 390
436643 AA757626 Hs 10941 ESTs Weakly similar to IPP1.HUMAN PROTE 390
416498 U33632 Hs 79351 potassium channel subfamily K member 1 390
413281 AA861271 Hs 222024 transcπpton factor BMAL2 390
446999 AA151520 hypothetical protein MGC4485 390
429610 AB024937 Hs 211092 LUNX protein, PLUNC (palate lung and nas 389
446356 AI816736 Hs 14896 DHHC1 protein 388
458997 AW937420 ESTs 388
440074 AA863045 Hs 10669 ESTs Weakly simllarto T00050 hypothet 388
436087 BE300296 Hs 5054 CGI-133 protein 387
4486,90 AK001304 Hs 21771 Wolf Hlrschhom syndrome candidate 2 387
446269 AW263155 Hs 14559 hypothetical protein FLJ 10540 386
449696 AW779666 Hs 266854 ESTs 386
444864 AW965446 Hs 81907 ESTs, Weakly slmilarto T26501 hypothet 385
424921 AA348491 Hs 322456 hypothetical protein DKFZp761D0211 385
412123 BE251328 Hs 73291 hypothetical protein FLJ10881 385
434725 AK000796 Hs 4104 hypothetical protein 385
408670 AF160967 Hs 46784 potassium large conductance calcium act 385
409151 AA306105 Hs 50785 SEC22, vesicle trafficking protein (S c 385
422956 BE545072 Hs 122579 ECT2 protein (Epithelial cell transforml 385
421662 NM 014141 Hs 106552 cell recognition molecule Caspr2 384
427674 NM 003528 Hs 2178 H2B histone family, member Q 384
441680 AW444598 HS 7940 RAP1, GTP GDP dissociation stimulator 1 383
440325 NM 003812 HS 7164 a dislntegrin and metalloprotelnase doma 383
434423 NM 006769 Hs 3844 LIM domain only 4 383
416586 D44643 Hs 14144 secreted modular calcium binding protein 382
413551 BE242639 Hs 75425 ubiquitn associated protein 381
425007 AA456483 Hs 172081 phosphodlesterase 4D, cAMP specific (dun 381
430399 AI916284 Hs 199671 ESTs 381
429345 R11141 Hs 199695 hypothetical protein 381
426722 U53823 Hs 171952 occludin 381
428227 AA321649 Hs 2248 small Inducible cytokine subfamily B (Cy 380
404632 NM.022490 Homo sapiens hypothetcal prot 380
432169 Y00971 Hs 2910 phosphoπbosyl pyrophosphate synthetase 380
420805 L10333 Hs 99947 retculon 1 380
411704 AI499220 Hs 71573 hypothetical protein FLJ10074 380
453891 AB037751 Hs 36353 Homo sapiens mRNA full length Insert cDN 380
435513 AW404075 Hs 42785 DC11 protein 380
445165 AV652831 Hs 234058 gb AV652831 GLC Homo sapiens cDNA clone 380
404571 NM.015902* Homo sapiens progestln Induce 380
455019 AW850818 gb IL3 CT0220 091199 026 A03 CT0220 Homo 379
426501 AW043782 Hs 293616 ESTs 379
407777 AA161071 Hs 71465 squalene epoxidase 379
442064 AI422867 Hs 88594 ESTs 379
440590 AI863446 Hs 266308 mosaic serine protease 378
441128 AA570256 ESTs, Weakly simllarto T23273 hypothet 375 407300 AA102616 Hs 120769 gb zn43e07 s1 Stratagene HeLa cell s393 375
419682 H13139 Hs 92282 paired like homeodomaln traπscπpton fa 375
411598 BE336654 Hs 70937 H3 hlstone family, member A 375
453900 AW003582 Hs 226414 ESTs, Weakly slmilarto ALU8.HUMAN ALU S 375
421202 AF193339 Hs 102506 eukaryotic translation initiation fador 375
423645 AI215632 Hs 147487 ESTs 375
455459 AW947654 gb RC0 MT0003 140300 031-b06 MT0003 Homo 375
411450 H49619 Hs 127301 ESTs 375
425842 AI587490 Hs 159623 NK-2 (Drosophila) homolog B 375
410935 BE067395 Hs 66881 dyneln, cytoplasmlc, Intermediate polype 374
447735 AA775268 Hs 6127 Homo sapiens cDNA FLJ23020 fis, clone L 374
454417 A1244459 Hs 110826 tπnucleotide repeat containing 9 374
408349 BE546947 Hs 44276 homeo box C10 373
439778 AL109729 Hs 99364 putative transmembrane protein 373
452012 AA307703 Hs 279766 kinesin family member 4A 370
400102 Eos Control 370
415621 AI648602 Hs 55468 ESTs 370
437866 AA156781 metallothloneln 1E (functional) 370
443687 F13040 KIAA1228 protein 370
428690 AI948490 Hs 98765 ESTs 370
450447 AF212223 Hs 25010 hypothetical protein P15 2 370
444946 AW139205 Hs 156457 hypothetical protein FLJ22408 370
427779 AA906997 Hs 180780 TERA protein 369
437929 T09353 Hs 106642 ESTs, Weakly slmilarto T09052 hypothet 368
439588 AA838166 Hs 174644 hypothetical protein FLJ21669 368
430044 AA464510 Hs 152812 ESTs 368
427982 NM 016156 Hs 181326 KIAA1073 protein 367
421180 BE410992 Hs 258730 heme regulated Initiation factor 2-alpha 365
434063 AA018893 Hs 3727 unr interacting protein 365
433701 AW445023 Hs 15155 ESTs 365
422390 AW450893 Hs 121830 ESTs, Weakly simllarto T42682 hypothet 365
451407 AA131376 Hs 343809 fibroblast growth factor 12B 365
421991 NM 014918 Hs 110488 KIAA0990 protein 365
429656 X05608 Hs 211584 neurofilament, light polypeptide (68kD) 365
415068 Z19448 Hs 131887 ESTs, Weakly simllarto T24396 hypothet 365
416198 H27332 Hs 99598 hypothetical protein MGC5338 365
425782 U66468 Hs 159525 cell growth regulatory with EF hand doma 365
452512 AW363486 Hs 337635 ESTs 365
446162 AI631319 Hs 63841 hypothetical protein DKFZp434E2318 365
402114 Target Exon 365
437204 AL110216 ESTs, Weakly similar to 155214 salivary 365
419354 M62839 Hs 1252 apolipoprotein H (beta 2 glycoprotein I) 365
448105 AW591433 Hs 298241 Transmembrane protease, serine 3 364
405204 NM.002086* Homo sapiens growth factor re 364
412314 AA825247 G protein coupled receptor 27 (GPR27) (S 364
427398 AW390020 Hs 20415 chromosome 21 open reading frame 11 364
418941 AA452970 Hs 239527 E1B 55kDa associated protein 5 364
433730 AK002135 Hs 3542 hypothetical protein FLJ11273 364
456439 AA251242 Hs 103238 ESTs 363
446783 AW138343 Hs 141867 ESTs 363
439211 AI890347 Hs 271923 Homo sapiens cDNA FLJ22785 fis, clone K 363
450516 AA902656 Hs 21943 NIF3 (Ngg1 interacting factor 3, S pombe 362
431933 AI187057 Hs 132554 ESTs 362
429084 AJ001443 Hs 195614 splicing factor 3b, subunlt 3 130kD 362
432284 AA532807 Hs 105822 ESTs 361
452833 BE559681 Hs 30736 KIAA0124 protein 361
447702 AI420256 Hs 161271 ESTs 360
449571 AW016812 Hs 200266 ESTs 360
414747 U30872 Hs 7204 centromere protein F (350/400kD, mitosln 360
431542 H63010 Hs 5740 ESTs 360
426788 U66615 Hs 172280 SWI/SNF related, matnx associated, act 360
415791 H09366 Hs 78853 uracll DNA glycosylase 360
440492 R39127 Hs 26966 hypothetical protein DKFZp547J036 359
457670 AF119666 Hs 23449 Insulin receptor tyrosine kinase substra 358
409262 AK000631 Hs 52256 hypothetical protein FLJ20624 357
446872 X97058 Hs 16362 pyπmldlnergic receptor P2Y, G protein c 3 57
414696 AF002020 Hs 76918 Nlemann Pick disease, type C1 357
436134 AK000618 Hs 123784 ESTs 357
427853 AI569798 Hs 98260 ESTs 357
414222 AL135173 Hs 878 sorbitol dehydrogenase 356
411285 AI733766 Hs 69429 Homo sapiens IMAGE 512024 clone, mRNA 355
453160 AI263307 H2B hlstone family, member L 355
422094 AF129535 Hs 272027 F box only protein 5 3 55
438118 AW753311 ESTs 355
429048 AI372949 Hs 44241 Homo sapiens cDNA FLJ21447 fis, clone C 355
432329 NM 002962 Hs 2960 S100 calcium binding protein A5 355
449318 AW236021 Hs 78531 Homo sapiens, Similar to RIKEN cDNA 5730 355
444151 AW972917 Hs 128749 alpha methylacyl CoA racemase 355
443450 N66045 Hs 133529 ESTs 355
453507 AF083217 Hs 33085 WD repeat domain 3 354
432540 AI821517 Hs 105866 ESTs 354
448664 AI879317 Hs 334691 splicing factor 3a, subunlt 1 , 120kD 354
402855 NM.001839* Homo sapiens calponlπ 3, add 354
453751 R36762 Hs 101282 Homo sapiens cDNA FLJ21238 fis, clone C 353
403817 NM.015271 Homo sapiens tπpartite motif 353
427471 AA403131 Hs 266782 KIAA1826 protein 352 431387 AI878854 Hs 252229 v-maf musculoaponeurotc fibrosarcoma (a 352
415947 U04045 Hs 78934 utS (E coli) homolog 2 (colon cancer, 352
438523 H66220 Hs 278177 ESTs 351
452874 AK001061 Hs 30925 hypothetcal protein FLJ10199 351
453033 AA325869 Hs 31463 KIAA0281 gene product 350
439605 AF086431 Hs 22380 ESTs 350
453785 AI368236 Hs 283732 ESTs, Moderately similar to ALU1 HUMAN A 350
434970 AW272262 Hs 225767 ESTs 350
406081 Target Exon 350
430712 AW044647 ESTs 350
420912 AW853156 Hs 90787 ESTs 350
411096 U80034 Hs 68583 mltochondrial intermediate peptidase 350
418338 NM 002522 Hs 84154 neuronal pentraxin I 350
409902 AI337658 Hs 156351 ESTs 350
406685 M18728 gb Human nonspecific crossreactng antlg 349
442045 C05768 Hs 8078 Homo sapiens clone FBD3 Cπ du chat cnt 349
440773 AA352702 Hs 37747 Homo sapiens, Similar to RIKEN cDNA 2700 349
408393 AW015318 Hs 23165 ESTs 349
446825 BE266822 Hs 344097 filamin A, alpha (actiπ-blnding protein 348
450937 R49131 Hs 26267 ATP dependant Interferon response protei 348
421948 L42583 Hs 334309 keratin 6A 347
448296 BE622756 Hs 10949 Homo sapiens cDNA FLJ14162 fis, clone NT 347
459709 AA653774 Hs 212084 ESTs 347
412507 L36645 Hs 73964 EphA4 346
442426 AI373062 Hs 332938 hypothetical protein MGC5370 346
438956 W00847 Hs 135056 Human DNA sequence from clone RP5 850E9 346
435092 AL137310 Hs 4749 Homo sapiens mRNA, cDNA DKFZp761E13121 ( 345
443347 AI052543 Hs 133244 melanoma denved leucine zipper, extra n 345
411261 AW834655 gb MR2-TT0014-291199 017-g11 TT0014 Homo 345
416658 U03272 Hs 79432 fibnllln 2 (congenital contractural ara 345
453941 U39817 Hs 36820 Bloom syndrome 345
442353 BE379594 Hs 49136 ESTs, Moderately similar to ALU7.HU AN A 345
410206 NM 003826 Hs 60415 N θthylmaleimlde sensitive factor attach 345
441865 AA384726 Hs 5722 hypothetical protein FLJ23316 345
414602 AW630088 Hs 76550 Homo sapiens mRNA, cDNA DKFZp564B1264 (f 344
432229 AW290976 Hs 143587 ESTs 343
434808 AF155108 Hs 256150 NY REN 41 antigen 343
415632 U67085 Hs 78524 TcD37 homolog 343
441790 AW294909 Hs 132208 ESTs 342
438697 AA814439 ESTs 342
452827 AI571835 Hs 55468 ESTs 342
441805 AA285136 Hs 301914 neuronal specific transcnpton factor D 342
433149 BE257672 Hs 42949 hypothetical protein HES6 342
438832 AA827023 Hs 270981 hypothetical protein FLJ14397 341
425548 AA890023 Hs 1906 prolactn receptor 341
406304 transcriptional adaptor 3 (ADA3, yeast h 340
434844 AF157116 Hs 22350 hypothetical protein LOC56757 340
447669 AL049985 Hs 19180 Homo sapiens mRNA, cDNA DKFZp564E122 (fr 340
400884 Target Exon 340
411683 W01167 Hs 50426 ESTs 340
445242 BE156478 Hs 21108 ESTs Weakly similartoALUI HUMAN ALU S 340
424796 AW298244 Hs 266195 ESTs 340
422358 AL133030 Hs 115429 Homo sapiens mRNA for KIAA1666 protein, 340
404995 ENSP00000251890* Monocytc leukemia zinc 340
438525 AW368528 Hs 100855 ESTs 340
415263 AA948033 Hs 130853 ESTs 340
428753 AW939252 Hs 192927 hypothetical protein FLJ20251 340
449343 AI151418 protein phosphatase 3 (formerly 2B), cat 340
412863 AA121673 Hs 59757 zinc finger protein 281 340
424036 AA770688 H2A hlstone family, member L 340
452823 AB012124 Hs 30696 transcnpton factor-like 5 (basic helix 340
408437 AW957744 Hs 278469 lacπmal praline πch protein 339
415402 AA164687 Hs 177576 mannosyl (alpha 1,3 ) glycoprotein beta- 339
412722 AI343300 Hs 15091 ESTs 338
426793 X89887 Hs 172350 HIR (hlstone cell cycle regulaton defec 338
417366 BE185289 Hs 1076 small praline nch protein 1B (comifin) 338
422611 AA158177 Hs 118722 fucosyltransferase 8 (alpha (1 ,6) fucosy 338
452598 AI831594 ESTs, Weakly similar to ALU7.HUMAN ALU S 338
406981 S71129 acetylchollnesterase (YT blood group) 338
414844 AA296874 Hs 77494 deoxyguaπoslne kinase 337
409235 AA188827 Hs 7988 ESTs, Weakly similar to I38022 hypothet 337
436608 AA628980 Hs 192371 down syndrome cntcal region protein DS 336
415474 NM 014252 Hs 78457 solute carrierfamlly 25 (mltochondrial 336
447850 AB018298 Hs 19822 SEC24 (S cerevlslae) related gene famil 336
400583 Target Exon 336
419138 U48508 Hs 89631 ryanodlne receptor 1 (skeletal) 336
430188 AL049242 Hs 234794 Homo sapiens mRNA, cDNA DKFZp564B083 (fr 335
452323 W44356 Hs 292812 ESTs, Weakly similar to T33468 hypothet 335
437534 AA814471 Hs 23510 ESTs 335
441420 AA932872 gb oo57d07 s1 NCI_CGAP_LU5 Homo sapiens 335
420337 AW295840 Hs 14555 Homo sapiens cDNA FLJ21513 fis, clone C 335
408101 AW968504 Hs 123073 CDC2-related protein kinase 7 335
425769 U72513 Hs 159486 Human RPL13-2 pseudogene mRNA, complete 335
451806 NM 003729 Hs 27076 RNA 3'-termlnal phosphate cyclase 335
409673 AK000611 Hs 55781 hypothetical protein FLJ20604 335
410166 AK001376 Hs 59346 hypothetical protein FLJ10514 335 412673 AL042957 Hs 31845 ESTs 335
442326 H92962 Hs 124813 hypothetical protein MGC14817 335
410660 AI061118 Hs 65328 Fanconl anemia, complementation group F 335
442660 AW138174 Hs 130651 ESTs 335
442573 H93366 Hs 7567 branched chain amlnotransferase 1, cytos 335
447644 AW861622 Hs 108646 Homo sapiens cDNA FLJ14934 fis, clone PL 335
448752 AA593867 Hs 300842 KIAA1608 protein 334
402537 C1003560* gι|10435919|dbj|BAB14704 1| (A 333
432834 F06459 Hs 289113 cytochrome b5 reductase 1 (B5R 1) 333
418721 NM 002731 Hs 87773 protein kinase, cAMP dependent, catalyti 333
425424 NM.004954 Hs 157199 ELKL motif kinase 333
434340 AI193043 Hs 128685 ESTs, Weakly simllarto T17226 hypothet 332
443209 AI040125 Hs 150521 ESTs 332
401560 heparan sulfate (glucosamlne) 3-O-sulfot 331
447832 A1433357 ESTs 331
453469 AB014533 Hs 33010 KIAA0633 protein 331
426600 NM 003378 Hs 171014 VGF nerve growth factor inducible 330
435770 AA699991 Hs 348162 gb zi69a09 s1 Soares.fetaUiver.spleeπ. 330
410491 AA465131 Hs 64001 Homo sapiens done 25218 mRNA sequence 330
444070 NM 015367 Hs 10267 MIL1 protein 330
424332 AA338919 Hs 101615 ESTs 330
421768 AI923934 Hs 108112 hlstone fold protein CHRAC17, DNA polyme 330
425018 BE245277 Hs 154196 E4F transcπpton factor 1 330
430187 AI799909 Hs 158989 ESTs 330
452234 AW084176 Hs 223296 ESTs, Weakly slmilarto I38022 hypothet 330
440138 AB033023 Hs 318127 hypothetical protein FLJ10201 330
444743 AA045648 Hs 301957 nudlx (nucleoside diphosphate linked mol 330
411019 AW993097 Hs 48617 Homo sapiens cDNA FLJ12540 fis clone NT 330
438378 AW970529 Hs 86434 hypothetical protein FLJ21816 330
407204 R41933 Hs 140237 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 329
440704 M69241 Hs 162 Insulin like growth factor binding prate 329
441622 AW450957 Hs 224864 ESTs 329
425840 AW978731 Hs 301824 hypothetical protein PR01331 329
440006 AK000517 Hs 6844 NALP2 protein, PYRIN Containing APAF1 II 329
450291 AW015549 Hs 269199 ESTs 328
440282 BE262386 clones 23667 and 23775 zinc finger prate 327
440675 AW005054 Hs 279788 ESTs, Weakly slmilarto KCC1.HUMAN CALCI 327
424259 AK001776 Hs 143954 hypothetical protein FLJ10914 326
431130 NM 006103 Hs 2719 HE4, epldldymls-specific, whey-addic pr 326
436557 W15573 Hs 5027 ESTs, Weakly slmilarto A47582 B-cell gr 326
448045 AJ297436 Hs 20166 prostate stem cell antgen 326
409406 H83092 Hs 49605 ESTs 325
416677 T83470 Hs 334840 ESTs, Moderately similar to I78885 senn 325
422771 NM 012318 Hs 120165 leuclne zlpper-EF-hand containing transm 325
435005 U80743 Hs 306094 tπnucleotide repeat containing 12 325
422134 AW179019 Hs 112110 mltochondrial πbosomal protein L42 325
442152 R39246 Hs 239666 Homo sapiens cDNA FLJ13495 fis, clone PL 325
434804 AA649530 gb ns44f05 s1 NCI_CGAP_Alv1 Homo sapiens 325
422744 AW268803 Hs 119640 hBKLF for basic kruppel like factor 325
422420 U03398 Hs 1524 tumor necrosis factor (ligand) superfaml 325
435532 AW291488 Hs 117305 Homo sapiens, clone IMAGE 3682908, mRNA 325
429413 NM.014058 Hs 201877 DESC1 protein 325
404148 NM.002944* Homo sapiens v ros avian UR2 325
433183 AF231338 Hs 222024 transcπpton factor BMAL2 325
414523 AU076633 Hs 76353 seπne (or cystelne) protelnase inhibito 325
451418 BE387790 Hs 26369 hypothetical protein FLJ20287 325
427521 AW973352 ESTs 325
411945 AL033527 Hs 92137 L-myc 2 protein (MYCL2) 325
447155 AA100605 Hs 121557 ESTs, Weakly slmilarto DP1 HUMAN POLYPO 324
452737 AK001680 Hs 30488 DKFZP434F091 protein 324
411263 BE297802 Hs 69360 kinesin like 6 (mltotlc centromere-asεoc 324
435369 BE385785 Hs 323715 methionine adenosyltransferase I, alpha 324
410741 Z11695 Hs 324473 mltogen activated protein kinase 1 323
415192 D17793 Hs 78183 aldo keto reductase family 1, member C3 323
455416 AW937143 gb PM1-DT0041-281299 001-f01 DT0041 Homo 323
458187 D56919 Hs 265848 myomegalln 323
413129 AF292100 Hs 104613 RP42 homolog 323
415992 C05837 Hs 145807 hypothetical protein FLJ13593 323
416883 AW140128 Hs 184902 ESTs 323
414013 AA766605 Hs 47099 hypothetical protein FLJ21212 323
453454 AW052006 PRP4/STK/WD splicing factor 323
426181 AA371422 Hs 334371 hypothetical protein MGC13096 322
436995 Al 160015 Hs 125489 ESTs 322
428878 AA436884 Hs 48926 ESTs 322
411248 AA551538 Hs 69321 Homo sapiens cDNA FLJ14408 fis, clone HE 321
419381 AB023420 Hs 90093 heat shock 70kD protein 4 321
427490 Z95152 Hs 178695 mltogen activated protein kinase 13 321
417601 NM 014735 Hs 82292 KIAA0215 gene product 321
440273 AI805392 Hs 325335 Homo sapiens cDNA FLJ23523 fis, clone L 321
404891 Target Exon 320
438989 AW979100 gb EST391210 MAGE resequences, MAGP Homo 320
403416 KIAA0564 protein 320
454731 BE067650 gb MR4-BT0358-090300 003 e01 BT0358 Homo 320
414888 AL039185 Hs 77558 thyroid hormone receptor interactor 7 320
420650 AA455706 Hs 44581 heat shock protein hsp70 related protein 320
448686 AA158659 Hs 334712 hypothetical protein FLJ14744 320 450728 AW162923 Hs 25363 presenilln 2 (Alzheimer disease 4) 320
426581 AB040956 Hs 135890 KIAA1523 protein 320
442179 AA983842 Hs 333555 chromosome 2 open reading frame 2 320
422536 AA311915 Hs 187726 gb EST182621 Jurkat T-cells VI Homo sapi 320
447492 AI381619 Hs 20188 ESTs 320
457292 AI921270 Hs 281462 hypothetical protein FLJ14251 320
449704 AK000733 Hs 23900 GTPase activating protein 320
442577 AA292998 Hs 163900 ESTs 320
423942 AF209704 Hs 169407 glycolipid transfer protein 320
439696 W95298 Hs 171882 ESTs 319
409142 AL136877 Hs 50758 SMC4 (structural maintenance of chromoso 319
446639 AI016826 Hs 342148 ESTs 319
452144 AA032197 Hs 102558 Homo sapiens, clone MGC 5352, mRNA, comp 318
446054 AB014537 Hs 13604 KIAA0637 gene product 318
452126 AI859947 Hs 314158 ESTs, Weakly simllarto I38022 hypothet 318
426108 AA622037 Hs 166468 programmed cell death 5 318
451621 AI879148 Hs 26770 fatty add binding protein 7, brain 317
433913 AI694106 Hs 72325 ESTs, Weakly simllarto I38022 hypothet 317
427254 AL121523 Hs 97774 ESTs 316
430361 AI033965 Hs 239926 sterol-C4-methyl oxidase-like 316
450065 AL050107 Hs 24341 transcπptonal co activator with PDZ-bi 316
420090 AA220238 Hs 94986 πbonuclease P (38kD) 316
436481 AA379597 HS 5199 HSPC150 protein simllarto ubiquitln-con 316
435652 N32388 Hs 334370 uncharacteπzed hypothalamus protein HBE 315
453905 NM 002314 Hs 36566 LIM domain kinase 1 315
454425 AW300927 Hs 27192 hypothetical protein dJ1057B202 315
425419 AJ002078 Hs 157144 syntaxin 6 315
414271 AK000275 Hs 75871 protein kinase C binding protein 1 315
455751 BE075281 gb PM1-BT0585-290200-005-d07 BT0585 Homo 315
408673 BE208517 πbosomal protein L37a 315
405031 solute earner family 22 (organic caton 315
401216 C12000969 gι|7662320|ref|NP_055628 1| Kl 315
409463 AI458165 Hs 17296 hypothetical protein MGC2376 315
418506 AA084248 Hs 85339 Unknown protein for MGC 29643 (formerly 315
414396 BE548266 Hs 76057 galactose-4-epimerase, UDP- 314
418113 AI272141 Hs 83484 SRY (sex determining region Y)-box 4 314
433257 AA613437 Hs 302743 hypothetical protein FLJ 12543 314
442445 AA082665 Hs 209561 KIAA1715 protein 313
428375 T65153 Hs 104613 ESTs 313
430713 AA351647 Hs 2642 eukaryotic translation elongation factor 313
421116 T19132 Hs 101850 retnol-blnding protein 1, cellular 313
434573 AW372340 Hs 14337 ESTs 313
448102 AI750793 Hs 20295 CHK1 (checkpoint, S pombe) homolog 313
425159 NM.004341 Hs 154868 carbamoyl-phosphate synthetase 2, aspart 312
451336 AI264643 Hs 3610 ESTs 312
423613 AF036035 Hs 129910 hyaluronoglucosaminldase 3 312
430317 AB020645 Hs 239189 glutaminase 312
423541 AA296922 Hs 129778 seπne protease Inhibitor, Kazal type 4 312
403851 C5002154* gι|7299015|gb|AAF54217 1| (AE0 312
418422 AW440068 Hs 59425 hypothetical protein FLJ23323 311
427709 AI631811 Hs 180403 STRIN protein 310
440546 AI491994 gb to07g09 x1 NCI_CGAP_Ut2 Homo sapiens 310
437605 AW452716 Hs 13328 hypothetical protein FLJ20421 310
442543 AI869950 Hs 216039 ESTs 310
434438 AI654867 hemoglobin, beta 310
410627 AA181339 Hs 929 myosln, heavy polypeptide 7, cardiac mus 310
449505 AI653006 Hs 195374 ESTs 310
455510 AA422029 Hs 143640 ESTs, Weakly similar to hypeφolaπzatio 310
446715 AI337735 Hs 173919 ESTs, Moderately similar to ZN91.HUMAN Z 310
424539 L02911 Hs 150402 Activin A receptor, type 1 (ACVR1) (ALK 310
414040 N58513 Hs 32171 ESTs 310
443054 AI745185 Hs 84520 yβs-assoclated protein 65 kDa 310
425641 D79758 Hs 14355 Homo sapiens cDNA FLJ13207 fis, clone NT 310
423642 AW452650 Hs 157148 hypothetical protein MGC13204 310
459647 R34107 Hs 321450 pregnancy specific beta-1 -glycoprotein 1 310
422005 BE266556 Hs 110702 Homo sapiens mRNA, cDNA DKFZp761E212 (fr 310
431868 BE246400 Hs 285176 acetyl-Coenzyme A transporter 310
442530 AI580830 Hs 176508 Homo sapiens cDNA FLJ14712 fis, clone NT 310
433819 AW511097 Hs 112765 ESTs 310
453377 AI679149 Hs 167186 ESTs 310
449000 U69560 Hs 3826 kelch-llke protein C3IP1 310
411943 BE502436 Hs 7962 ESTs, Weakly simllarto S44608 C02F56 p 310
421610 AA393168 Hs 90034 hypothetical protein FLJ21916 310
422947 AA306782 Hs 122552 G-2 and S-phase expressed 1 310
434669 AF151534 Hs 92023 core hlstone macroH2A22 309
437108 AA434054 Hs 80624 hypothetical protein MGC2560 309
445033 AV652402 Hs 72901 cycliπ-depeπdent kinase Inhibitor 2B (p1 309
445138 H99085 gb yx18c06 s1 Soares melanocyte 2NbHM Ho 309
429901 AK000502 Hs 56237 hypothetical protein FLJ20495 309
420028 AB014680 Hs 8786 carbohydrate (N-acetylglucosamlne 6-0) s 309
436440 AI471862 Hs 196008 Homo sapiens cDNA FLJ11723 fis, clone HE 309
442366 AA115629 Hs 118531 ESTs 309
422684 BE561617 Hs 119192 H2A hlstone family, member Z 309
412122 AW852707 G-πch RNA sequence binding factor 1 309
440967 AK002092 HS 7570 hypothetical protein FLJ 11230 308
410211 NM 014347 Hs 296365 zinc finger protein 308 447245 AK001713 Hs 17860 hypothetical protein FLJ10851 308
422385 BE549407 Hs 115823 ribonuclease P, 40kD subunlt 308
437158 AW090198 KIAA1150 protein 307
424395 AA165082 Hs 146388 microtubule-associated protein 7 307
418478 U38945 Hs 1174 cyclin-dependent kinase Inhibitor 2A (me 307
428423 AU076517 Hs 184276 solute carπerfamily 9 (sodium/hydrogen 307
429504 X99133 Hs 204238 lipocalin 2 (oncogene 24p3) (NGAL) 307
444700 NM 003645 Hs 11729 fatty acid Coenzyme A ligase, very long- 306
442092 AW578669 hypothetical protein FLJ12439 306
432201 AI538613 Hs 298241 Transmembrane protease, seπne 3 306
446390 AA233393 Hs 14992 hypothetical protein FLJ11151 305
430396 D49742 Hs 241363 hyaluroπan-binding protein 2 305
446440 AV658411 Hs 42656 KIAA1681 protein 305
429873 AW268693 Hs 105713 ESTs 305
401203 Target Exon 305
458059 AW015588 Hs 137232 ESTs, Weakly simllarto S65657 alpha 1C- 305
417975 AA641836 Hs 30085 hypothetical protein FLJ23186 305
459672 Z18867 Hs 326843 gb HSDHEGC03 Stratagene cDNA library Hum 305
451365 AI791783 Hs 16063 ESTs, Weakly simllarto ALU8.HUMAN ALU S 305
450687 AA495800 gb zw05b07 s1 Soares.NhHMPu.S1 Homo sapl 305
410976 R36207 Hs 25092 hypothetical protein MGC10744 305
441318 AI078234 ESTs 305
433553 AA825523 ESTs, Weakly slmilarto I38022 hypothet 305
447437 U07225 Hs 339 puππergic receptor P2Y, G protein coupl 305
454442 AW816134 Hs 132967 gb MR3 ST0220-290100 016 e04 ST0220 Homo 305
407876 NM 004519 Hs 40866 potassium voltage-gated channel, KQT lik 305
410507 AA355288 transitional eplthella response protein 305
404440 NM.021048 Homo sapiens melanoma antigen, 305
419865 NM 007020 Hs 93502 U1-snRNP binding protein homolog (70kD) 305
410561 BE540255 Hs 6994 Homo sapiens cDNA FLJ22044 fis, clone H 305
418248 NM 005000 Hs 83916 NM 005000* Homo sapiens NADH dehydrogena 305
450824 R09055 Hs 22011 ESTs Weakly similar to I38022 hypothet 305
426216 N77630 Hs 13895 Homo sapiens cDNA FLJ 11654 fis, clone HE 305
443098 AI247833 Hs 139265 ESTs, Moderate)yslmllartoALU1 HUMAN A 304
414388 BE281412 gb 601154911F1 NIH_MGC_21 Homo sapιeπsc 304
427308 D26067 Hs 174905 KIAA0033 protein 304
451035 AU076785 Hs 430 plastn 1 (I isoform) 304
440726 AL050333 Hs 306425 DKFZP564B116 protein 304
441991 AW844404 Hs 126901 Homo sapiens mRNA full length Insert cDN 304
433090 AI720050 Immortalizaton upregulated protein 304
407792 AI077715 Hs 39384 putative secreted ligand homologous to f 304
435641 AI147545 Hs 114172 ESTs 303
417542 J04129 Hs 82269 progestagen associated endometrial prate 303
425997 AK000086 Hs 165948 hypothetical protein FLJ20079 303
439924 AI985897 Hs 125293 ESTs 303
453968 AA847843 Hs 62711 High mobility group (nonhistone chromoso 303
415015 NM.002109 Hs 77798 histdyl tRNA synthetase 302
400183 Eos Control 302
448826 AI580252 Hs 293246 ESTs, Weakly slmilarto putative p150 [H 301
420085 AI741909 Hs 44680 hypothetical protein FLJ20979 301
429248 U96759 Hs 198307 von Hlppel Llndau binding protein 1 301
409892 AW956113 Hs 7149 gb EST368183 MAGE resequences, MAGD Homo 300
405942 Target Exon 300
455286 BE144384 gb MR0-HT0166-191199 004-c11 HT0166 Homo 300
420301 AA767526 Hs 22030 paired box gene 5 (B cell lineage specif 300
407382 AA503620 gb ne49b08 s1 NCI_CGAP_Co3 Homo sapiens 300
403011 ENSP00000215330* Probable senne/threonl 300
445076 AI206888 Hs 154131 ESTs 300
418857 D10216 Hs 89394 POU domain, class 1 , transcription facto 300
426572 AB037783 Hs 170623 hypothetical protein FLJ11 83 300
411506 T75366 Hs 146286 kinesin family member 13A 300
434301 AF124512 Hs 221660 blood vessel eplcardial substance 300
412530 AA766268 Hs 266273 hypothetical protein FLJ13346 300
403882 Target Exon 300
458918 H56499 Hs 252692 ESTs, Weakly slmilarto 138022 hypothet 300
445704 AI493742 Hs 167700 ESTs, Moderately similar to 138022 hypot 300
438703 AI803373 Hs 31599 ESTs 300
451378 BE153447 gb PM2-HT0338 131299 001-b01 HT0338 Homo 300
444165 AL137443 Hs 10441 hypothetical protein FLJ11236 300
403532 NM.024638 Homo sapiens hypothetcal prot 300
453468 W00712 Hs 32990 DKFZP566F084 protein 300
440278 BE560870 Hs 9052 ESTs, Weakly simllarto 2004399A chromos 300
456251 R13326 Hs 326475 ESTs 300
425673 R70318 Hs 339730 ESTs 300
442619 AA447492 Hs 20183 ESTs Weakly similar to AF164793 1 prote 300
459119 AW844498 Hs 306121 CDC20 (cell division cycle 20, S cerevi 300
455440 AW946022 gb QVO-ET0001-050500-229 b08 ET0001 Homo 300
413832 AI913647 Hs 131886 Homo sapiens cDNA FLJ22113 fis, clone H 300
421515 Y11339 Hs 105352 GalNAc alpha-2, 6-sialyltransferase I, I 300
437994 U92012 Hs 251659 ESTs, Weakly similar to mariner transpos 300
418827 BE327311 Hs 47166 HT021 300
420610 AI683183 Hs 99348 distal-less homeo box 5 300
401435 C14000397* gll7499898|pir||T33295 hypoth 300
447072 D61594 Hs 17279 tyrosylproteln sulfotransferase 1 300
411975 AI916058 Hs 144583 3 UTR of dead πnger (Drosophila) like 299
400965 C11002190" gl|12737279|ref|XP_012163 1| 299 430594 AK000790 Hs 246885 hypothetical protein FLJ20783 298
436469 AK001455 HS 5198 Down syndrome cπtlcal region gene 2 298
421433 AI829192 Hs 22380 ESTs 298
407756 AA116021 Hs 38260 ublquitm specific protease 18 298
433658 L03678 Hs 156110 immunoglobulin kappa constant 298
449969 AW295142 Hs 180187 Homo sapiens cDNA FLJ14337 fis, clone PL 298
441962 AW972542 Hs 289008 Homo sapiens cDNA FLJ21814 fis, clone H 297
432241 AI937060 Hs 6298 KIAA1151 protein 297
412560 R24601 CCR4-N0T transcπptlon complex, subunlt 297
433323 AA805132 Hs 159142 ESTs 297
447444 AK000318 Hs 18616 hypothetical protein FLJ20311 297
425465 L18964 Hs 1904 protein kinase C, iota 297
410337 M83822 Hs 62354 cell division cycle 4 like 297
424800 AL035588 Hs 153203 MyoD family Inhibitor 297
406709 AI355761 Hs 242463 keratin 8 296
411412 AJ001388 Hs 69997 zinc finger protein 238 296
426761 AI015709 Hs 172089 PORIMIN Pro oncosls receptor Inducing me 296
456564 AW747802 gb QV1-BN0003061299 040 b09 BN0003 Homo 296
437273 AL137451 Hs 120873 ESTs, Highly similar to T46266 hypothet 296
426820 U73328 Hs 172648 distal less homeobox 4 296
449209 BE616830 Hs 294145 ESTs 296
402025 NM.021624 Homo sapiens histamine H4 rece 295
416178 AI808527 Hs 192822 seroiogically defined breast cancer ant 295
446719 W39500 Hs 301872 hypothetical protein MGC4840 295
428500 AI815395 Hs 184641 fatty acid desaturase 2 295
417879 R22128 gb yh25h08 r1 Soares placenta Nb2HP Homo 295
404173 Target Exon 295
404819 NM.002688* Homo sapiens peanut (Drosophi 295
448718 AA220235 Hs 153959 hypothetical protein MGC15436 295
402270 Target Exon 295
420362 U79734 Hs 97206 huntngtin interacting protein 1 295
451815 AW974911 Hs 184793 Homo sapiens cDNA FLJ21880 fis, clone H 295
445921 AW015211 Hs 146181 ESTs 295
429412 NM 006235 Hs 2407 POU domain, class 2, associating factor 295
442875 BE623003 Hs 23625 Homo sapiens clone TCCCTA00142 mRNA sequ 295
407804 AF228603 Hs 39957 pleckstππ 2 (mouse) homolog 295
420569 AA278362 Hs 289062 Homo sapiens cDNA FLJ12334 fis, clone MA 295
436389 AI811706 Hs 42733 CHMP1 5 protein 295
424581 M62062 Hs 150917 catenin (cadhenn associated protein), a 295
406749 AW193917 Hs 217493 aπnexiπ A2 295
418295 AW970043 Hs 238039 hypothetical protein FLJ11090 295
431310 AW327889 Hs 252433 Homo sapiens cDNA FLJ13794 fis, clone TH 295
434698 BE044674 gb hm46f02 x1 NCI.CGAP.RDF1 Homo sapiens 295
430316 NM 000875 Hs 239176 insulin like growth factor 1 receptor 295
439210 AA641928 Hs 194071 ESTs, Weakly slmilarto unnamed protein 295
414052 AW578849 Hs 283552 ESTs, Weakly simllarto unnamed protein 295
418304 AA215702 gb zr97g10 rl NCI CGAP GCB1 Homo sapiens 295
440327 R12581 Hs 191146 ESTs 294
431707 R21326 Hs 267905 hypothetical protein FLJ 10422 294
458898 AW295097 Hs 200260 ESTs 293
408471 NM 012317 Hs 45231 leuclne zipper, down-regulated In cancer 293
418526 BE019020 Hs 85838 solute earner family 16 (monocarboxylic 293
446111 W56338 Hs 13880 CG1 143 protein 293
410444 W73484 Hs 132554 gb zd54e04 s1 Soares_fetal_heart_NbHH19W 293
439396 BE562958 Hs 74346 hypothetical protein MGC14353 292
433627 AF078866 Hs 284296 Homo sapiens cDNA FLJ22993 fis, clone K 292
425683 AB037813 Hs 159200 hypothetical protein DKFZp762K222 292
452480 AI903526 gb RC BT031 090199 063 BT031 Homo sapien 291
458247 R14439 Hs 209194 ESTs 291
410682 H07103 Hs 286014 Homo sapiens, clone IMAGE 3867243, mRNA 291
445733 BE295568 Hs 13225 UDP-Gal betaGlcNAc beta 1 ,4- galactosylt 291
429986 AF092047 Hs 227277 sine oculis homeobox (Drosophila) homolo 291
419638 N46504 Hs 91747 profllin 2 291
414983 L17128 Hs 77719 gamma-glutamyl carboxylase 291
442643 U82756 PRP4/STK/WD splicing factor 290
416361 AW204907 Hs 6872 ESTs, Weakly similar to CA13.HUMAN COLLA 290
437575 AW954355 Hs 36529 hypothetical protein MGC11242 290
431214 AA294921 Hs 348024 v-ral simian leukemia viral oncogene hom 290
414064 BE245289 Hs 16165 expressed In activated T/LAK lymphocytes 290
446258 AI283476 Hs 263478 ESTs 290
404607 Target Exon 290
414094 H15088 Hs 31433 ESTs 290
443833 AI654108 Hs 135125 ESTs 290
442712 BE465168 Hs 131011 ESTs 290
411887 AW182924 Hs 128790 ESTs 290
405366 NM.003371* Homo sapiens vav 2 oncogene ( 290
404624 karyopheπn (Importln) beta 3 290
411387 AW842339 Hs 130815 hypothetical protein FLJ21870 290
408990 AL022395 Hs 49526 f-box and leucine rich repeat protein 4 290
417288 AI984792 Hs 108812 hypothetical protein FLJ22004 290
419465 AW500239 Hs 21187 Homo sapiens cDNA FLJ23068 fis, clone L 290
459010 AA331438 gb EST35269 Embryo, 8 week I Homo sapien 290
445008 AW373754 gb QV4 BT0536291299-065 e01 BT0536 Homo 290
412170 D16532 Hs 73729 very low density lipoproteln receptor 2 90
419752 AA249573 Hs 152618 ESTs, Moderately slmilarto ZN91.HUMAN Z 290
419497 NM 006410 Hs 90753 Tat-lntera iπg protein (30kD) 290 423849 AL157425 Hs 133315 Homo sapiens mRNA, cDNA DKFZp761 J1324 (f 290
452909 NM 015368 Hs 30985 pannexin 1 290
428560 AI243209 Hs 98669 ESTs, Weakly slmilarto B47411 ADPπbosy 290
413429 BE139117 Hs 278881 ESTs 290
426126 AL118747 Hs 26691 AY046419 Homo sapiens glucose transport 289
409693 AA010233 Hs 55921 glutamyl-prolyl-tRNA synthetase 289
407242 M18728 gb Human nonspecific crossreacting antig 289
412174 C04144 Hs 172753 ESTs 289
447541 AK000288 Hs 18800 hypothetical protein FLJ20281 288
409264 NM 014937 Hs 52463 KIAA0966 protein 288
453063 W47196 Hs 166172 aryl hydrocarbon receptor nuclear transl 288
431865 AA521106 Hs 136375 ESTs, Weakly similar to S65824 reverse t 288
409231 AA446644 Hs 692 GA733-2 antigen, epithelial glycoprotein 288
424364 AW383226 Hs 163834 ESTs, Weakly slmilarto G01763 atrophin- 287
408713 NM 001248 Hs 47042 ectonucleoside tπphosphate diphosphohyd 287
406972 M32053 gb Human H19 RNA gene, complete eds 287
404901 NM 025213 Homo sapiens spectnn, beta, n 287
422939 AW394055 Hs 98427 ESTs, Weakly slmilarto I38022 hypothet 287
449824 AI962552 Hs 226765 ESTs 287
409728 AW883968 Hs 321190 ESTs 287
418867 D31771 Hs 89404 msh (Drosophila) homeo box homolog 2 287
429492 W21183 Hs 13205 ESTs 287
429023 NM 000312 Hs 2351 protein C (inactlvator of coagulaton fa 286
416612 H70565 gb yr97c04 Soares fetal liver spleen 286
440457 BE387593 Hs 21321 Homo sapiens clone FLB9213 PR02474 mRNA, 286
446620 AA128808 Hs 179902 transporter-like protein 286
413517 N76712 Hs 44829 ESTs, Weakly slmilarto I38022 hypothet 286
448475 BE613134 Hs 247474 hypothetical protein FLJ21032 286
433167 AB037682 Hs 195715 hypothetical protein MGC4827 286
406137 NM.000179* Homo sapiens mutS (E coll) h 285
457094 AI360119 Hs 181013 phosphoglycerate mutase 1 (brain) 285
428792 BE535955 Hs 193602 chromosome condensation protein G 285
410305 AF030409 Hs 62185 solute earner family 9 (sodium/hydragen 285
408253 AW807476 Hs 21051 Homo sapiens mRNA for FLJ00012 protein, 285
430355 NM 006219 Hs 239818 phosphoιπositιde-3 kinase, catalytc, be 285
436854 AA749167 Hs 173911 ESTs 285
412783 BE276738 Hs 74578 DEAD/H (Asp-Glu-Ala-Asp/His) box polypep 285
406303 C16000922 gι|7499103|plr||T20903 hypothe 285
432917 NM 014125 Hs 241517 PR00327 protein 285
430452 A1888450 Hs 174644 hypothetical protein FLJ21669 285
422805 AA436989 Hs 121017 H2A hlstone family, member A 285
441642 H85686 Hs 7922 HSPC154 protein 285
443614 AV655386 Hs 7645 flbrinogen, B beta polypeptide 285
419270 NM 005232 Hs 89839 EphA1 285
448807 A1571940 Hs 7549 ESTs 285
413838 AV661185 Hs 75574 mltochondrial πbosomal protein L19 285
412831 AA121352 Hs 143314 ESTs 285
429370 C19097 Hs 89709 glutamate-cysteine ligase, modifier subu 285
438895 AW007021 Hs 82894 ESTs 285
440516 S42303 Hs 161 cadheπn 2, type 1, N cadheπn (neuronal 284
451721 NM 006946 Hs 26915 spectrin, beta, non-erythrocytc 2 284
407813 AL120247 Hs 40109 KIAA0872 protein 284
417386 AL037228 Hs 82043 D123 gene product 284
441021 AW578716 Hs 7644 H1 hlstone family, member 2 284
444184 T87841 Hs 282990 Human DNA sequence from clone RP1-28H20 284
416946 NM 012324 mltogen-activated protein kinase 8 inter 284
432734 AA837396 Hs 263925 LlS1-interacting protein NUDE1, rat homo 284
426779 AA384577 Hs 93714 ESTs, Weakly similar to T00365 hypothet 284
437679 NM 014214 Hs 5753 inosltol(myo)-1 (or 4)-monophosphatase 2 284
427722 AK000123 Hs 180479 hypothetical protein FLJ20116 284
423692 BE621056 Hs 131731 hypothetical protein FLJ11099 283
445654 X91247 Hs 13046 thloredoxln reductase 1 283
415276 U88666 Hs 78353 SFRS protein kinase 2 283
429038 AL023513 Hs 194766 seizure related gene 6 (mouse)-lιke 283
432375 BE536069 Hs 2962 S100 calcium binding protein P 282
424481 R19453 Hs 1787 proteollpld protein 1 (Pelizaeus-Merzbac 282
418027 AB037807 Hs 83293 hypothetical protein 282
429978 AA249027 ribosomal protein S6 282
421486 AW408800 Hs 104859 hypothetical protein DKFZp762E1312 282
436972 AA284679 Hs 25640 claudin 3 282
437786 BE142681 Hs 155573 polymerase (DNA directed), eta 281
438881 AA827691 Hs 129967 ESTs, Weakly similar to ALU1.HUMAN ALU S 281
408901 AK001330 Hs 48855 hypothetical protein FLJ10468 281
416984 H38765 Hs 80706 dlaphorase (NADH/NADPH) (cytochrome b-5 281
422559 AW247696 Hs 155839 hypothetcal protein MGC12934 281
422259 AA307584 gb EST178498 Colon carcinoma (HCC) cell 281
448789 BE539108 Hs 22051 hypothetical protein MGC15548 281
453164 F33692 Hs 32018 SNARE associated protein snapln 281
414670 BE409525 Hs 902 neurolibromln 2 (bilateral acoustic neur 281
424971 AA479005 Hs 154036 tumor suppressing subtransferable candid 281
417381 AF164142 Hs 82042 solute earner family 23 (nucleobase tra 280
408681 AW953853 Hs 281462 ESTs, Weakly slmilarto I38022 hypothet 280
459208 BE261314 Hs 250469 ESTs, Weakly simllarto I38022 hypothet 280
445133 AW157646 Hs 198689 ESTs 280
455236 AW875972 gb CM3-PT0014 071299-051-b05 PT0014 Homo 280
426647 AA243464 Hs 294101 pre-B-cell leukemia transcription factor 280 411954 AA652523 Hs 269496 ESTs, Weakly similar to I38022 hypothet 280
426925 NM 001196 Hs 315689 Homo sapiens cDNA FLJ22373 fis, clone H 280
425128 BE561929 Hs 154718 tumor protein D52-like 2 280
432642 BE297635 Hs 3069 heat shock 70kD protein 9B (mortalin-2) 280
416128 AA173632 CDC14 (cell division cycle 14, S cerevi 280
427342 AL110150 Hs 176680 Homo sapiens mRNA, cDNA DKFZp586D0724 (f 280
419544 AI909154 gb QV-BT200-010499-007 BT200 Homo sapien 280
450214 BE439763 Hs 227571 regulator of G protein signalling 4 280
403848 arylsulfatase E (chondrodysplasia puncta 280
448002 Y15227 Hs 20149 deleted in lymphocyte leukemia, 1 280
431999 AL133573 Hs 272312 Homo sapiens mRNA, cDNA DKFZp434J2235 (f 280
402261 C19001033* gi|6754398|ref|NP_036071 1| J 280
415660 AI909007 Hs 78563 ublquitπ conjugating enzyme E2G 1 (homo 280
428134 AA421773 Hs 161008 ESTs 280
437147 AL049964 hypothetical protein FLJ20366 280
442562 BE379584 dollchyl dlphosphooligosacchaπde-protei 280
423441 R68649 Hs 278359 absent In melanoma 1 like 280
436211 AK001581 Hs 334828 hypothetical protein FLJ10719, KIAA1794 280
437341 AA749062 ESTs, Weakly similar to I54374 gene NF2 280
454453 AW752781 hypothetical protein FLJ12614 slmilarto 280
434723 W17044 Hs 327337 ESTs 279
442553 H87867 Hs 40065 hypothetical protein MGC4825 279
432728 NM.006979 Hs 278721 HLA class II region expressed gene KE4 279
409132 AJ224538 Hs 50732 protein kinase, AMP-adivated, beta 2 no 279
453863 X02544 Hs 572 orosomucoid 1 279
447604 AW089933 Hs 301342 hypothetical protein MGC4342 279
432195 AJ243669 Hs 8127 KIAA0144 gene product 279
448850 AB018286 Hs 247837 neurexln 3 279
445800 AA126419 Hs 32944 Inositol polyphosphate 4 phosphatase, ty 279
449019 AI949095 Hs 67776 ESTs, Weakly similar to T22341 hypothet 278
452747 BE153855 Hs 61460 Ig superfamily receptor LNIR 278
409190 AU076536 Hs 50984 sarcoma amplified sequence 278
446080 AI221741 Hs 117777 ESTs 278
442476 AF069475 gb AF069475 Homo sapiens astracytoma lib 278
414907 X90725 Hs 77597 polo (Drosophia) like kinase 278
451150 AI888124 Hs 285280 Homo sapiens cDNA FLJ22096 fis, clone H 278
438182 AW342140 Hs 182545 ESTs, Weakly similarto ALU1 HUMAN ALU S 278
420164 AW339037 Hs 24908 ESTs 278
422404 AL133571 Hs 336189 Homo sapiens mRNA, cDNA DKFZp434F1135 (f 277
451958 AW207328 ESTs 277
444895 AI674383 Hs 22891 solute carπerfamily 7 (catoπic amino 276
421260 N46574 Hs 43838 ESTs 276
443507 AI769289 Hs 22383 hypothetical protein FLJ11336 276
446383 T05816 Hs 92511 ESTs 276
424118 BE269041 Hs 140452 cargo selection protein (mannose 6 phosp 276
407699 AA825974 Hs 32646 hypothetical protein FLJ21901 276
422170 AI791949 Hs 112432 ant Mulleπan hormone 276
400294 N95796 Hs 278695 Homo sapiens prostein mRNA, complete eds 276
441181 AA416925 peptidylprolyl isomerase (cyclophilm) 1 276
415889 R24563 VPS10 domain receptor protein 275
400821 Target Exon 275
416814 AW192307 Hs 80042 dollchyl P-Glc Man9GlcNAc2-PP-dollchylgl 275
400857 ENSP00000228038* PUTATIVE SERINE7THREONI 275
411666 AF106564 Hs 71346 neurofilament 3 (150kD medium) 275
444185 AW298350 Hs 113602 ESTs 275
443385 AI792839 Hs 133113 ESTs 275
445873 AA250970 Hs 251946 po!y(A) binding protein, cytoplasmic 1-1 275
441102 AA973905 intermediate filament protein syncollin 275
411630 U42349 Hs 71119 Putatvβ prostate cancer tumor suppresso 275
456193 H43437 Hs 80305 hypothetical protein MGC14258 275
421342 AA504749 gb aa63f08 r1 NCI CGAP GCB1 Homo sapiens 275
419507 AW170425 Hs 87680 ESTs 275
439602 W79114 Hs 58558 ESTs 275
453775 NM 002916 Hs 35120 replication factor C (activator 1) 4 (37 275
438054 AA776626 Hs 169309 ESTs 275
423598 BE247600 Hs 155538 ESTs 275
407771 AL138272 Hs 1600 ESTs 275
423492 AF020761 Hs 129683 ublqultn-conjugatng enzyme E2D 1 (homo 275
422336 AI761322 Hs 115285 dlhydrolipoamide S acetyltransferase (E2 275
409717 AW452871 Hs 56043 CGI-115 protein 275
447818 W79940 Hs 21906 Homo sapiens clone 24670 mRNA sequence 275
414361 AI086138 Hs 204044 ESTs 275
424840 D79987 Hs 153479 extra spindle poles, S cerevlslae, homo 275
442711 AF151073 Hs 8645 hypothetical protein 275
436561 BE560135 Hs 5232 HSPC125 protein 275
408576 NM 003542 Hs 46423 H4 hlstone family, member G 274
443724 AA446783 Hs 288932 hypothetical protein FLJ13194 274
441057 AL043897 ESTs 274
450983 AA305384 Hs 25740 ER01 (S cerevlslae) like 273
420230 AL034344 Hs 284186 forkhead boxd 273
424873 AB018294 Hs 153610 KIAA0751 gene product 273
452960 AK001335 Hs 31137 protein tyrosine phosphatase, receptor t 273
442861 AA243837 Hs 57787 ESTs 273
416801 X98834 Hs 79971 sal (Drosophila)-llke 2 273
423250 BE061916 Hs 125849 chromosome 8 open reading frame 2 273
416959 D28459 Hs 80612 ublquitn-conjugating enzyme E2A (RAD6 h 273 413719 BE439580 Hs 75498 small Inducible cytokine subfamily A (Cy 273
446100 AW967109 Hs 13804 hypothetical protein dJ4620232 273
442404 A1733500 Hs 124370 ESTs 273
412988 BE046680 gb hn42h03 x1 NCLCGAP.RDF2 Homo sapiens 272
421582 AI910275 trefoil factor 1 (breast cancer, estroge 272
434288 AW189075 Hs 116265 flbπlllrfl 272
418461 BE242781 Hs 102971 hypothetical protein FLJ14751 272
454462 AW754153 Hs 155976 cullin 4B 272
451089 AA903705 Hs 4190 Homo sapiens cDNA FLJ23269 fis, clone C 272
441436 AW137772 Hs 185980 ESTs 271
430227 AI924441 Hs 236218 TAT-INTERACTIVE PROTEIN, 72 KD 271
417089 H52280 Hs 18612 Homo sapiens cDNA FLJ21909 fis, clone H 271
403671 C4001270* gl|7509005|pir||T26190 hypothe 271
436895 AF037335 Hs 5338 carbonic anhydrase XII 271
435474 W92102 Hs 117269 ESTs 271
408405 AK001332 Hs 44672 hypothetical protein FLJ10470 271
420319 AW406289 Hs 96593 hypothetical protein 270
419329 AY007220 Hs 288998 S100 type calcium binding protein A14 270
402280 C19002023 gl|12741355|ref|XP_012768 1| z 270
415208 F01020 Hs 172004 in 270
400240 Eos Control 270
405976 Target Exon 270
400074 Eos Control 270
432093 H28383 gb yl52c03 r1 Soares breast 3NbHBst Homo 270
435579 AI332373 Hs 156924 ESTs 270
443323 BE560621 Hs 9222 estrogen receptor binding site associate 270
412505 AA974491 Hs 21734 ESTs 270
451311 D61040 gb HUM149E10B Clontech human fetal brain 270
437025 AW296618 Hs 120637 ESTs 270
414429 R51494 Hs 71818 ESTs 270
432188 AI362952 Hs 2928 solute carrierfamlly 7 (catonic ammo 270
457873 AA736920 Hs 288518 ESTs 270
455290 U75810 gb HSU75810 Human Homo sapiens cDNA cloπ 270
447678 BE385257 Hs 63908 Homo sapiens dopamlne receptor Interact 270
429782 NM.005754 Hs 220689 Ras GTPase activating protein SH3 domain 270
406203 Target Exon 270
419030 T79957 Hs 188466 ESTs 270
444911 U06117 Hs 250 xanthene dehydrogenase 270
456759 BE259150 Hs 127792 delta (Drosophila) like 3 270
445564 AB028957 Hs 12896 KIAA1034 protein 270
428816 AA004986 Hs 193852 ATP binding cassette sub family C (CFTR 270
416800 H89652 gb yu81f05 r1 Soares fetal liver spleen 270
418104 T05726 Hs 177130 ESTs 270
409435 AI810721 Hs 95424 ESTs 270
412926 AI879076 Hs 75061 macrophage mynstoylated alanine πch C 270
436876 AI124756 Hs 5337 isocitrate dehydrogenase 2 (NADP) mitoc 270
447400 AK000322 Hs 18457 hypothetical protein FLJ 20315 269
452436 BE077546 Hs 31447 ESTs, Moderately similar to A46010 X lln 269
409775 AW499605 gb Ul HF BPOp ain c-050 Ul r1 NIH.MGC.5 269
450222 U75308 Hs 24644 TATA box binding protein (TBP) associate 269
414416 AW409985 Hs 76084 hypothetical protein MGC2721 269
452567 D87120 Hs 29882 predicted osteoblast protein 269
421485 AA243499 Hs 104800 hypothetical protein FLJ10134 269
402609 KIAA1209 protein 269
419741 NM 007019 Hs 93002 ublquitn earner protein E2 C 268
417715 AW969587 Hs 86366 ESTs 268
411669 BE612676 Hs 303116 stromai cell-denved factor 2 like 1 268
439424 AI478667 Hs 118183 hypothetical protein FLJ 22833 268
409590 AW997069 Hs 99010 hypothetical protein FLJ22263 simllarto 268
402927 ENSP00000243914* DJ579F202 (simllarto 268
409529 AB007884 Hs 54697 Cdc42 guanine exchange factor (GEF) 9 268
450816 BE271927 Hs 87385 ESTs 268
416221 BE513171 Hs 79086 mitochondπal πbosomal protein L3 267
427505 AA361562 Hs 178761 26S proteasome associated padl homolog 267
424629 M90656 Hs 151393 glutamate cystelne llgase, catalytc sub 267
428844 AW972635 Hs 301904 hypothetical protein FLJ12671 267
453464 AI884911 Hs 32989 receptor (caldtonln) activity modifying 267
422424 AI186431 Hs 296638 prostate differentiation factor 267
410703 AW798089 gb CM0 UM0045 030300-262 c05 UM0045 Homo 267
418385 AW590613 Hs 301040 Homo sapiens clone IMAGE 3357127, mRNA 267
430301 AI902657 Hs 188662 KIAA1702 protein 267
403324 C2000428*gI|7705383|ref|NP_057536 1| GC 267
430532 D61216 Hs 18672 ESTs 267
426153 AF057169 Hs 182771 vltelliform macular dystrophy (Best dlse 267
435602 AF217515 Hs 283532 uncharacteπzed bone marrow protein BM03 267
450669 AL138077 Hs 16157 hypothetical protein FLJ12707 267
450587 AI828854 Hs 258538 stnatn, calmodulln binding protein 267
452256 AK000933 Hs 28661 Homo sapiens cDNA FLJ10071 fis, clone HE 267
446525 AW967069 Hs 211556 hypothetical protein MGC5487 267
450273 AW296454 Hs 24743 hypothetical protein FLJ20171 266
409361 NM 005982 Hs 54416 sine oculls homeobox (Drosophila) homolo 266
452826 BE245286 Hs 301636 peroxlsomal biogenesis factor 6 266
429500 X78565 Hs 289114 hexabrachloπ (tenascin C, cytotactn) 266
444476 AF020038 Hs 11223 isocitrate dehydrogenase 1 (NADP), solub 266
400528 NM.020975* Homo sapiens ret proto-oncoge 266
423445 NM.014324 Hs 128749 alpha methylacyl CoA racemase 266 419704 AA429104 Hs 45057 ESTs 266
442923 AW248322 Hs 95835 ESTs, Weakly simllarto unnamed protein 266
445786 AW629819 Hs 144502 hypothetical protein FLJ22055 266
445707 AI248720 Hs 114390 ESTs 266
410575 BE207480 Hs 6994 Homo sapiens cDNA FLJ22044 fis, clone H 265
435327 BE301871 Hs 4867 mannosyl (alpha-1,3-)-glycoproteln beta- 265
428788 AF082283 Hs 193516 B-cell CLL/lymphoma 10 265
447776 AI525625 Hs 130181 UDP-N-acetyl-alpha-D-galactosamlne polyp 265
442604 BE263710 gb 601192150F1 NIH MGC.7 Homo sapiens cD 265
445572 AI243445 Hs 189654 ESTs 265
436581 AA725726 Hs 180213 ESTs 265
450671 Al 356967 Hs 43086 ESTs, Weakly similar to A46010 X-linked 265
424238 AA337401 Hs 137635 ESTs 265
404478 NM.015435 Homo sapiens double ππg-finge 265
402265 Target Exon 265
414872 U82010 Hs 77513 COX10 (yeast) homolog, cytochrome c oxld 265
450927 AI807804 Hs 134342 TASP for tests-specific adriamycln sens 265
447673 AI823987 Hs 182285 ESTs 265
424686 AA345504 gb EST51529 Gall bladder II Homo sapiens 265
420210 AI557257 Hs 44811 ESTs 265
452451 AA311250 Hs 5621 ESTs, Weakly simllarto A46010 X-liπked 265
449570 AA001793 gb zh86c06 r1 Soares.fetaljlver.spleen. 265
410252 AW821182 Hs 61418 mlcrofibπllar-associated protein 1 265
428186 AW504300 Hs 295605 mannosldase, alpha, class 2A, member 2 265
453878 AW964440 Hs 19025 DC32 265
435274 AA887547 Hs 150905 ESTs 265
430001 AI580056 Hs 98992 ESTs 265
401796 NM.021213* Homo sapiens phosphatldylchol 265
401783 NM.003771* Homo sapiens keratin, hair, a 265
419362 N64116 Hs 24624 hypothetical protein FLJ21945 265
455737 BE072246 gb QV4-BT0536-271299 059 b12 BT0536Homo 265
408161 AW952912 Hs 300383 hypothetical protein MGC3032 265
436488 BE620909 Hs 261023 hypothetical protein FLJ20958 265
424736 AF230877 Hs 152701 mlcrotubule-interactiπg protein that ass 265
444656 AI277924 Hs 145199 ESTs 265
422516 BE258862 Hs 117950 multfunctonal polypeptide similar to S 265
431070 AW408164 Hs 249184 transcnpton factor 19 (SC1) 265
418166 AI754416 Cdc42 effector protein 3 265
402553 C1001756* gl|2143875|pir||l73636 neurona 265
447587 AW292139 Hs 115789 ESTs 264
424339 BE257148 endoglycan 264
424723 BE409813 Hs 152337 protein arglnme N methyltransferase 3(h 264
431842 NM.005764 Hs 271473 epithelial protein up-regulated In card 264
445101 T75202 Hs 12314 Homo sapiens mRNA, cDNA DKFZp586C1019 (f 264
419234 AI565714 Hs 101660 ESTs 264
429617 X89984 Hs 211563 B-cell CLL/lymphoma 7A 264
458513 AI138322 Hs 154894 ESTs 263
422872 BE326786 Hs 187646 ESTs 263
433980 AA137152 Hs 286049 phosphoseπne amlnotransferase 263
458692 BE549905 Hs 231754 ESTs 263
435607 W73428 Hs 8750 uncharacteπzed bone marrow protein BM04 263
412141 AI183838 Hs 48938 hypothetical protein FLJ21802 263
448857 BE264467 Hs 117929 ESTs 263
441616 BE569122 RNA binding protein (autoantlgenic) 263
438472 AW974907 Hs 86228 TRIAD3 protein 262
415214 AI445236 Hs 125124 EphB2 262
421810 AK001718 Hs 108530 hypothetical protein FLJ10856 262
434811 AW971205 Hs 114280 ESTs 262
423081 AF262992 Hs 123159 sperm associated antigen 4 262
418655 AA226354 Hs 111240 ESTs 262
412760 AW379030 Hs 41324 ESTs 262
417848 AA206581 Hs 116586 ESTs, Weakly slmilarto JC5314 CDC28/cdc 262
405558 Target Exon 261
423450 AJ290445 Hs 128759 KIAA0524 protein 261
420071 AB028985 Hs 94806 ATP-binding cassette, sub family A (ABC1 261
430654 AW970081 Hs 325603 ESTs 261
412756 N27422 ESTs, Moderately similar toZ195_HUMAN Z 261
429045 AA443751 Hs 191819 ESTs, Weakly similar to I38022 hypothet 260
453392 U23752 Hs 32964 SRY (sex determining region Y)-box 11 260
404576 Target Exon 260
426028 NM 001110 Hs 172028 a dlsintegπn and metalloprotelnase doma 260
451862 H09260 Hs 32333 ESTs 260
416505 H66470 Hs 16004 ESTs 260
417807 R17806 Hs 269452 gb yg09b06 r1 Soares infant brain 1NIB H 260
418105 AW937488 Hs 246381 ESTs, Weakly similar to FV1 MOUSE FRIEND 260
401924 ENSP00000246632* CDNAFLJ20261 fis, clon 260
436027 AI864053 Hs 39972 GM2 ganglloslde activator protein (GM2A) 260
451446 AI826288 Hs 171637 hypothetical protein MGC2628 260
406389 C5001408* gi|12621134|ref|NP_0752441| M 260
433906 AI167816 Hs 43355 ESTs 260
404156 C6002456 gil6755268|reflNP_036008 1| RAS 260
418771 AA807881 Hs 172792 ESTs 260
420270 AA257990 Hs 137427 ESTs 260
445371 AI221645 Hs 147800 ESTs 260
439453 BE264974 Hs 6566 thyroid hormone receptor Interactor 13 260
415857 AA866115 Hs 127797 Homo sapiens cDNA FLJ11381 fis, clone HE 260 445326 AI220072 ESTs 260
416921 N20177 Hs 205024 ESTs, Highly similar to B34087 hypotheti 260
432723 D29677 Hs 3085 KIAA0054 gene product, Hellcase 260
408031 AA081395 Hs 42173 Homo sapiens cDNA FLJ 10366 fis, clone NT 260
431567 N51357 Hs 260855 Homo sapiens cDNA FLJ21410 fis, clone C 260
417183 R52089 Hs 172717 ESTs 260
448663 BE614599 hypothetical protein MGC14797 260
430393 BE185030 Hs 241305 estrogen-responsive B box protein 260
407325 AA291180 Hs 328476 ESTs, Weakly slmilarto alternatively sp 260
430408 AA478540 Hs 108336 ESTs, Weakly simllarto ALUE.HUMAN llll 259
418838 AW385224 Hs 35198 ectonucleotde pyrophosphatase/phosphodi 259
409937 AI804584 Hs 57672 leuclne πch repeat (in FLU) interactin 259
446937 AA977190 ESTs 259
439343 AF086161 Hs 114611 hypothetical protein FLJ 11808 259
434449 AW953484 Hs 3849 hypothetical protein FLJ22041 slmilarto 259
456161 BE264645 Hs 282093 hypothetical protein FLJ21918 259
429294 AA095971 Hs 198793 Homo sapiens cDNA FLJ22463 fis clone H 259
423357 AI285124 ESTs 259
410359 R38624 Hs 106313 ESTs 259
426357 AW753757 Hs 12396 gb RC3 CT0283 271099 021 a08 CT0283 Homo 259
450378 AW249181 Hs 198899 ESTs, Weakly slmilarto T19873 hypothet 258
409710 C04706 Hs 42733 CHMP1 5 protein 258
452526 W38537 Hs 280740 hypothetical protein MGC3040 258
414774 X02419 Hs 77274 plasmlnogen activator, uroklnase 258
432435 BE218886 Hs 282070 ESTs 258
448069 U76248 Hs 20191 seven in absentia (Drosophila) homolog 2 258
423279 AW959861 Hs 290943 ESTs 258
428708 NM 014897 Hs 190386 KIAA0924 protein 258
432026 AA524545 Hs 224630 ESTs 257
447333 BE090580 Hs 70704 hypothetical protein dJ616B83 257
426272 AW450671 Hs 189284 ESTs 257
447380 AA743756 Hs 116695 ESTs, Weakly slmilarto I38022 hypothet 257
407881 AW072003 Hs 40968 heparan sulfate (glucosamlne) 3 O-sulfot 257
456906 AF117646 Hs 156637 Cas Br M (murine) ectropic retroviral tr 257
416065 BE267931 Hs 78996 proliferating cell nuclear antigen 257
407590 AI831258 ESTs 257
429170 NM 001394 Hs 2359 dual specificity phosphatase 4 257
408246 N55669 Hs 333823 mltochondπal nbosomal protein L13 257
440660 AI300101 Hs 131886 Homo sapiens cDNA FLJ22113 fis, clone H 256
422630 AA313606 Hs 13809 hypothetical protein FLJ10648 256
410913 AL050367 Hs 66762 Homo sapiens mRNA, cDNA DKFZp564A026 (fr 256
456940 H46986 Hs 31861 ESTs 256
429588 AI080271 ESTs 256
427227 AF103803 Hs 283690 hypothetical protein 256
447347 AA570056 Hs 122730 ESTs, Moderately similar to KIAA1215 pro 256
411423 AW845987 Hs 68864 ESTs, Weakly similar to phosphatidylseπ 256
437175 AW968078 Hs 87773 protein kinase, cAMP dependent, catalyti 256
445652 AL117473 Hs 13036 DKFZP727A071 protein 256
422421 AA325138 Hs 235873 hypothetical protein FLJ22672 256
440115 R41808 Hs 144924 ESTs, Weakly simllarto B Chain B, Solut 255
421508 NM 004833 Hs 105115 absent in melanoma 2 255
447532 AK000614 Hs 18791 hypothetical protein FLJ20607 255
404580 tπchorhinophalangeal syndrome I gene (T 255
444454 BE018316 Hs 11183 sorting nexin 2 255
421557 AA292875 Hs 97333 ESTs 255
456370 AA234938 Hs 87384 ESTs 255
444161 N52543 Hs 142940 ESTs 255
419647 AA348947 Hs 91816 hypothetical protein 255
437231 BE303000 Hs 288929 hypothetical protein FLJ13258 slmilarto 255
456210 N49729 Hs 129819 ESTs 255
435410 AL135067 Hs 117182 ESTs 255
411136 AW845266 gb IL2 CT0031-160999 003 B08 CT0031 Homo 255
444461 R53734 Hs 25978 ESTs, Weakly similar to 2109260A B cell 255
446035 NM 006558 Hs 13565 Sam68 like phosphotyrosine protein, T-ST 255
426901 AA827922 ESTs 255
437919 AA772006 Hs 121630 ESTs 255
428264 AA424839 Hs 98484 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 255
413374 NM 001034 Hs 75319 πbonucleotide reductase M2 polypeptide 255
431917 D16181 Hs 2868 peripheral myelin protein 2 255
412115 AK001763 Hs 73239 hypothetical protein FLJ10901 255
439708 AI761369 Hs 59584 hypothetical protein FLJ21144 255
428782 X12830 Hs 193400 interleukin 6 receptor 255
444091 AV647924 Hs 282376 ESTs 255
434490 AF143870 Hs 15246 ESTs 255
427677 NM 007045 Hs 180296 FGFR1 oncogene partner 255
422296 AA360231 Hs 114416 Homo sapiens, Simllarto traπsducln (bet 255
407788 BE514982 Hs 38991 S100 calcium binding protein A2 254
430375 AW371048 Hs 93758 H4 hlstone family, member H 254
456249 AI206144 Hs 82508 HRIHFB2206 protein 254
458981 AW968318 Hs 285996 hypothetical protein FLJ23375 254
445075 AI651827 ESTs 254
442795 AW027935 Hs 251351 ESTs, Moderately similar to ALU8 HUMAN A 254
451945 BE504055 Hs 211420 ESTs 254
405418 Target Exon 254
432878 BE386490 Hs 279663 Plπn 254
434011 AW953437 Hs 5486 clone FLB5214 253 432942 AF083955 Hs 279852 G protein-coupled receptor 253
403291 Target Exon 253
425139 AW630488 Hs 25338 protease, serine, 23 253
448209 AW160489 Hs 20709 tetraspan 5 253
434629 AA789081 Hs 4029 glioma amplified sequence 41 253
447973 AB011169 Hs 20141 simllarto S cerevlslae SSM4 253
454294 AB000734 Hs 50640 JAK binding protein 252
446982 AW500221 Hs 43616 gb Ul HF BN0 akd c 03 0-UI r1 NIH.MGC.50 252
419735 AW750056 Hs 169577 Homo sapiens cDNA FLJ 14743 fis, clone NT 252
431657 AI345227 Hs 105448 ESTs, Weakly simllarto B34087 hypotheti 252
447898 AW969638 Hs 112318 62 kd protein 252
457370 AW970998 gb EST383083 MAGE resequences, MAGK Homo 252
442276 AI253193 Hs 129185 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 252
439465 AF086285 Hs 336620 Homo sapiens, Similar to RIKEN cDNA 4930 252
450074 AI367213 Hs 14070 hypothetical protein FLJ14166 252
424441 X14850 Hs 147097 H2A hlstone family, member X 252
427295 AW291212 Hs 293943 hypothetical protein MGC11266 252
424006 AF054815 Hs 137548 CD84 antigen (leukocyte antgen) 252
413326 H88621 Hs 19762 ESTs, Weakly slmilarto KIAA1140 protein 252
443790 NM.003500 Hs 9795 acyl Coenzyme A oxldase 2, branched chal 252
400995 C11000295* gi|12737279|ref|XP_012163 1| 252
419767 W73306 Hs 306668 Homo sapiens cDNA FLJ14089 fis, clone MA 251
405357 NM.003371* Homo sapiens vav 2 oncogene ( 251
424720 M89907 Hs 152292 SWI/SNF related, matπx associated, act 251
408839 AW277084 gb xp61h09 1 NCI CGAP Ov39 Homo sapiens 251
414591 AI888490 Hs 55902 ESTs, Weakly similar to ALU8 HUMAN ALU S 251
403055 C2002219* gι|12737280|ref|XP_0066822| k 251
437810 BE246399 hypothetical protein 251
413599 AJ006239 Hs 75438 quinoid dihydropteπdine reductase 251
451259 NM 006052 Hs 26146 Down syndrome cπtical region gene 3 251
410817 AI262789 Hs 93659 protein disulfide isomerase related prat 251
439943 AW083789 Hs 124620 ESTs 251
409889 AW630041 Hs 56937 suppression of tumoπgenlcity 14 (colon 251
430168 AW968343 Hs 145582 DKFZP434I1735 protein 251
428144 BE269243 Hs 182625 VAMP (vesicle associated membrane protei 250
402102 Target Exon 250
401759 Target Exon 250
453899 AW134536 Hs 243994 ESTs 250,
405510 ENSP00000233779* Hypothetical 680 kDa p 250
442186 AA984083 Hs 269746 ESTs, Weakly slmilarto T03306 PSD 95/SA 250
423748 AI149048 Hs 30211 hypothetical protein FLJ22313 250
434378 AA631739 Hs 335440 EST 250
420390 AA330047 Hs 191187 ESTs 250
400272 Eos Control 250
427161 AI024595 Hs 97508 a disiπtegπn and metalloprotelnase doma 250
446251 AW867156 Hs 282589 ESTs, Weakly simllarto I38022 hypothet 250
413472 BE242870 Hs 75379 solute earner family 1 (glial high affi 250
410386 W26187 Hs 3327 Homo sapiens cDNA FLJ22219 fis, clone H 260
447698 AI420156 Hs 326733 ESTs 250
456946 T29678 Hs 166068 villin 1 250
431328 AA502999 Hs 291591 ESTs 250
456583 AF179897 Hs 104105 Mels (mouse) homolog 2 250
433636 AA603041 Hs 296370 ESTs 250
420325 AA676544 Hs 171545 HIV-1 Rev binding protein 250
422637 AA399024 Hs 118836 myoglobm 250
446586 N58790 Hs 268820 ESTs 250
420520 AK001978 Hs 98510 similar to rabl 1-binding protein 250
438280 AW015534 Hs 217493 annexin A2 250
448822 BE149845 Hs 289038 hypothetical protein MGC4126 250
456497 AW967956 Hs 123648 ESTs, Weakly slmilarto AF1084601 ubinu 250
400298 AA032279 Hs 61635 six transmembrane epithelial antigen of 250
450277 AI690071 Hs 283552 ESTs, Weakly simllarto unnamed protein 250
431719 AW191608 Hs 77719 ESTs, Moderately similar to I38022 hypot 250
409706 BE158773 Hs 213207 ESTs 250
420807 AA280627 Hs 57846 ESTs 250
451722 H86374 Hs 40861 ESTs 250
450341 N90956 Hs 17230 hypothetical protein FLJ22087 250
438552 AJ245820 HS 6314 type I transmembrane receptor (seizure r 250
430289 AK001952 Hs 238039 hypothetical protein FLJ11090 250
416224 NM 002902 Hs 79088 retculocalbln 2, EF-hand calcium blndin 250
418372 AA311833 Hs 84318 replication protein A1 (70kD) 249
442229 AI885776 HS 8164 Mullbrey nanism 249
409175 Y15057 Hs 50905 serlne/threonine kinase 9 249
420676 AI434780 Hs 4248 vav 2 oncogene 249
433078 AW015188 Hs 121575 Homo sapiens cDNA FLJ12231 fis, clone MA 249
432788 AA521091 Hs 178499 Homo sapiens cDNA FLJ23117 fis, clone L 249
425811 AL039104 Hs 159557 karyopherin alpha 2 (RAG cohort 1 , Impor 249
448256 BE614149 Hs 20814 CGI-27 protein 249
402842 ENSP00000241325* DJ947L8 1 3 (novel CUB 248
422799 AI933199 Hs 120911 neurexophllin 4 248
419517 AF052107 Hs 90797 Homo sapiens clone 23620 mRNA sequence 248
451253 H48299 Hs 26126 claudin 10 248
453155 AF052126 Hs 552 steroid 5 alpha reductase, alpha polypep 248
429282 N27596 Hs 21342 ESTs 248
440334 BE276112 Hs 7165 zinc finger protein 259 248
437852 BE001836 Hs 256897 putative GPCR 247 433339 AF019226 Hs 8036 glloblastoma overexpressed 247
425145 BE242802 Hs 154797 KIAA0090 protein 247
401696 Target Exon 247
421877 AW250380 Hs 109059 mitochondπal πbosomal protein L12 247
427351 AW402593 Hs 123253 hypothetical protein FLJ22009 247
413835 AI272727 Hs 249163 fatty acid hydroxylase 247
407863 AA317089 Hs 597 glutamlc oxaloacetc transamiπase 1, sol 247
441960 R84940 Hs 17118 hypothetical protein FLJ11730 247
410099 AA081630 KIAA0036 gene produd 247
405484 C3002124* gi|12737280|ref|XP_0066822| k 247
430105 X70297 Hs 2540 cholinerglc receptor, nicotinlc, alpha p 246
436823 AW749865 Hs 117077 ESTs, Weakly slmilarto I38022 hypothet 246
412754 AW166375 Hs 74565 amyloid beta (A4) precursor-like protein 246
412646 NM 006825 Hs 74368 transmembrane protein (63kD), endoplasmi 246
436865 AW880358 Hs 339808 hypothetical protein FLJ10120 246
451653 W18193 ESTs, Moderately similar to HERC2 [H sap 246
416097 BE387371 Hs 118964 hypothetical protein FLJ20085 246
448474 AI792014 Hs 13809 hypothetical protein FLJ10648 246
410686 AI733735 Hs 114905 IRE1, S cerevlslae, homolog of 245
40B872 AI476139 Hs 13291 ESTs 245
407843 BE155223 gb PM1 HT0350 070100006 b01 HT0350 Homo 245
413010 AA393273 Hs 75133 transcnpton factor 6 like 1 (mitochond 245
453070 AK001465 Hs 31575 SEC63, endoplasmlc retculum translocon 245
427944 AA417878 Hs 48401 ESTs, Moderately similar to ALU8.HUMAN A 245
428169 AI928984 Hs 182793 golgl phosphoproteln 2 245
410855 X97795 Hs 66718 RAD54 (S cerevisiae) like 245
434530 AU077027 Hs 3887 proteasome (prosome macropaln) 26S subu 245
459071 Al 992083 Hs 346566 ESTs 245
425516 BE000707 Hs 29567 ESTs 245
413230 R72391 Hs 16512 hypothetical protein FLJ21079 245
405010 Target Exon 245
438578 AA811244 ESTs 245
405704 NM 001844* Homo sapiens collagen, type I 245
408629 N58905 Hs 119206 ESTs 245
415069 AA159831 Hs 29286 ESTs, Weakly simllarto 149636 DNA bindi 245
437748 AF234882 Hs 5814 suppression of tumongenlclty 7 245
411402 BE297855 Hs 69855 NRAS related gene 245
406671 AA129547 Hs 285754 met proto oncogene (hepatocyte growth fa 245
407321 AA156538 Hs 22546 gb zo34c06 s1 Stratagene colon (937204) 245
408418 AW963897 Hs 44743 KIAA1435 protein 245
443230 T80789 Hs 132973 ESTs 245
442329 AA991795 Hs 129289 ESTs 245
446782 AI653048 Hs 144006 solute earner family 6 (neurotransmitte 245
410062 AW974756 Hs 46476 ESTs 245
425170 AU077315 Hs 154970 transcπpton factor CP2 245
445571 AI378000 Hs 158489 ESTs, Weakly slmilarto Z184.HUMAN ZINC 245
450684 AA872605 Hs 25333 Interleukin 1 receptor, type II 245
420608 BE548277 Hs 103104 ESTs 245
418882 NM 004996 Hs 89433 ATP binding cassette, sub family C (CFTR 245
424081 NM 006413 Hs 139120 πbonuclease P (30kD) 245
431242 AA987742 Hs 347534 KIAA1201 protein 245
439492 AF086310 Hs 103159 ESTs 245
434360 AW015415 Hs 127780 ESTs 245
420747 BE294407 Hs 99910 phosphofructokinase, platelet 245
403167 Target Exon 245
429227 AI961456 Hs 21275 hypothetical protein FLJ11011 245
435800 AI248285 Hs 118348 ESTs 244
409935 AW511413 Hs 278025 ESTs 244
407712 X66893 Hs 37953 Faπconl anemia complementation group C 244
449112 BE564123 Hs 23060 DKFZP564F0522 protein 244
420460 AA262331 Hs 48376 Homo sapiens clone HB 2 mRNA sequence 244
431044 U93850 Hs 259855 elongation factor 2 kinase 244
416817 AA398045 Hs 104679 ESTs 244
429604 AK001B51 Hs 210778 hypothetical protein FLJ10989 244
410717 AW817608 Hs 130849 peptide deformylase like protein 244
428028 U52112 Hs 182018 Interleukin 1 receptor associated kinase 244
424572 M19650 Hs 179600 2 ,3' cyclic nucleotide 3' phosphodleste 244
448100 AV655272 Hs 20252 novel Ras family protein 244
435468 AW362803 Hs 166271 ESTs 244
448112 AW245919 Hs 34969 hypothetical protein DKFZp566N034 243
428242 H55709 Hs 2250 leukemia Inhibitory factor (cholinerglc 243
400247 Eos Control 243
439955 AW203959 Hs 149532 ESTs 243
424135 AW994455 Hs 140978 Homo sapiens mRNA, cDNA DKFZp762H106 (fr 243
417534 NM.004998 Hs 82251 myosln IE 243
405276 NM.019854 Homo sapiens HMT1 (hnRNP methy 243
403349 ephrlπ-B3 243
443281 AI042304 Hs 4635 dihydrolipoamlde dehydrogenase (E3 compo 243
411358 R47479 Hs 94761 KIAA1691 protein 243
423493 AI815965 Hs 129683 ublqultn conjugatng enzyme E2D 1 (homo 243
432586 AA568548 ESTs 243
423393 R37772 Hs 21420 p21 actvated protein kinase 6 242
407907 AI752235 Hs 41270 procollagen lysine, 2-oxoglutarate 5-dlo 242
418699 BE539639 Hs 173030 ESTs, Weakly similar to ALU8.HUMAN ALU S 242
432828 AB042326 Hs 287402 chondroltn 4-sulfotransferase 242
447388 AW630534 Hs 76277 Homo sapiens, clone MGC 9381, mRNA, comp 242 432623 AA557351 Hs 152448 ESTs, Moderately similar to S 14147 mult 242
442452 AI479592 Hs 324342 ESTs 242
446777 AW138243 ESTs 242
405451 Homo sapiens glutamlnyl peptde cyclotra 242
428166 AA423849 Hs 79530 M5 14 protein 241
419705 AW368634 Hs 154331 ESTs 241
403961 Target Exon 241
422243 AW803733 Hs 23585 hypothetical protein MGC12250 241
441941 AI953261 Hs 169813 hypothetical protein FLJ 23040 241
457332 AA961694 Hs 105187 kinesin protein 9 gene 241
424511 BE300512 Hs 193557 ESTs, Moderately similar to ALU7.HUMAN A 241
431563 AI027643 Hs 120912 ESTs 241
447501 AI954692 Hs 159400 ESTs 241
418650 BE386750 Hs 86978 prolyl endopeptidase 241
415558 AA885143 Hs 125719 ESTs 241
450791 R84948 Hs 60473 RFamide related peptde precursor 241
427673 AI989709 gb s35101 x1 NCI_CGAP_GC6 Homo sapiens 241
437576 BE514383 prothymosin, alpha (gene sequence 28) 240
417831 H16423 Hs 82685 CD47 antigen (Rh related antigen, integr 240
421778 AA428000 Hs 283072 actn related protein 2/3 complex, subun 240
449082 BE387561 Hs 22981 DKFZP586M1523 protein 240
410219 T98226 Hs 171952 occludln 240
431583 AL042613 Hs 262476 S adenosylmethlonine decarboxylase 1 240
446173 BE565849 Hs 14158 copine III 240
409929 R38772 Hs 172619 myelin transcnpton factor 1 like 240
405863 Target Exon 240
417587 AI911492 Hs 12489 ESTs 240
434159 AW135214 Hs 191828 ESTs 240
448964 N63996 Hs 289083 ESTs 240
425216 U81504 Hs 155172 adaptor-related protein complex 3, beta 240
430448 AI633553 Hs 13303 Homo sapiens cDNA FLJ21784 fis, clone H 240
414754 AW938668 gb PM1-DT0063 160200 003 C07 DT0063 Homo 240
443073 AI032321 ESTs 240
450904 R07118 Hs 189924 ESTs 240
425908 BE281602 Hs 161751 zinc finger protein 256 240
412846 AW961245 Hs 55896 Homo sapiens PAC clone RP5 978E18 from 7 240
415641 Z44481 gb HSC21E071 normalized infant brain cDN 240
405258 Target Exon 240
445866 H20899 Hs 13399 Homo sapiens clone 25032 mRNA sequence 240
402412 Target Exon 240
447842 AW160804 Hs 247302 twisted gastrulaton 240
434405 AF171055 Hs 20030 Homo sapiens thloredoxln reductase 3 (TR 240
428328 AA426080 Hs 292812 ESTs Weakly similar to I38022 hypothet 240
400567 Target Exon 240
453374 AI990091 Hs 75893 ankynn 3, node of Ranvler (ankyπn G) 240
429250 H56585 Hs 198308 tryptophan πch basic protein 240
426996 AW968934 Hs 173108 Homo sapiens cDNA FLJ21897 fis, clone H 240
442607 AA507576 Hs 288361 Homo sapiens cDNA FLJ22696 fis, clone H 240
440534 BE561168 gb 601344888F1 NIH.MGC 8 Homo sapiens cD 240
420968 AW968775 ESTs 240
443829 AI087954 Hs 23348 S phase kinase associated protein 2 (p45 240
417581 R26968 Hs 24104 ESTs, Weakly simllarto ALU7.HUMAN ALU S 240
442072 AI740832 Hs 12311 Homo sapiens clone 23570 mRNA sequence 240
443197 Z43613 gb HSC1GD091 normalized Infant brain cDN 240
412193 AI684467 Hs 144057 ESTs 240
408826 AF216077 Hs 48376 Homo sapiens clone HB 2 mRNA sequence 240
422321 AA906427 Hs 181035 hypothetical protein MGC11296 240
447769 AW873704 Hs 320831 Homo sapiens cDNA FLJ14597 fis, clone NT 240
422631 BE218919 Hs 118793 hypothetical protein FLJ10688 240
447958 AW796524 Hs 68644 Homo sapiens mlcrosomal signal peptdase 240
423430 AF112481 Hs 128501 RAD54, S cerevlslae, homolog of, B 240
422981 AF026445 Hs 122752 TATA box binding protein (TBP) associate 240
418330 BE409405 ESTs 240
434627 AI221894 Hs 39311 ESTs 240
445098 AL050272 Hs 12305 DKFZP566B183 protein 240
446711 AF169692 Hs 12450 protocadheπn 9 240
447495 AW401864 Hs 18720 programmed cell death 8 (apoptosis indue 240
450825 AC005954 Hs 25527 tight juncton protein 3 (zona occludens 240
421526 AL080121 Hs 105460 DKFZP564O0823 protein 240
431605 AW972407 Hs 124370 gb EST384498 MAGE resequences, MAGL Homo 239
429612 AF062649 Hs 252587 pituitary tumor transforming 1 239
419170 BE002798 Hs 287850 integral membrane protein 1 239
437271 AL137445 Hs 28846 Homo sapiens mRNA, cDNA DKFZp5660134 (fr 239
458097 AW341135 Hs 58104 ESTs 239
426105 AW962732 gb EST374805 MAGE resequences, MAGG Homo 239
414075 U11862 Hs 75741 amiloride binding protein 1 (amine oxlda 239
445994 NM 004724 Hs 13512 ZW10 (Drosophila) homolog, centromere/ki 239
420186 NM.015925 Hs 95697 liver-specific bHLH Zip transcription fa 239
404109 C6000844* gl|7497891|pir||T20194 hypothe 239
431341 AA307211 Hs 251531 proteasome (prosome, macropaln) subunlt 239
409703 NM 006187 Hs 56009 2'-5'-ollgoadenylate synthetase 3 (100 k 239
445834 AI913290 Hs 145532 ESTs, Weakly simllarto FV1 MOUSE FRIEND 238
449636 AI656608 Hs 281328 ESTs, Weakly similar to T00378 KIAA0641 238
425081 X74794 Hs 154443 minlcnromosome maintenance deficient (S 238
414368 W70171 Hs 75939 undine monophosphate kinase 238
431698 AI492369 ESTs 238 431549 AA507036 Hs 170673 ESTs 238
418731 AI264688 Hs 1197 heat shock 10kD protein 1 (chaperoπm 10 238
414111 BE047679 Hs 152982 hypothetical protein FLJ13117 238
431356 AW499632 Hs 288512 Homo sapiens cDNA FLJ11632 fis, clone HE 238
443048 AW013982 Hs 250114 ESTs 238
431049 AA846576 Hs 103267 hypothetical protein FLJ22548 simllarto 238
409129 AW296699 Hs 103521 seπne arglnlne-πch pre-mRNA splicing f 238
453323 AF034102 Hs 32951 solute earner family 29 (nucleoside tra 237
449022 NM 016331 Hs 22879 zinc finger protein ANC.2H01 237
418068 AW971155 Hs 293902 ESTs, Weakly simllarto ISHUSS protein d 237
431317 AA502682 gb ng23d01 s1 NCI_CGAP_Ov2 Homo sapiens 237
430315 NM 004293 Hs 239147 guanine deamlnase 237
443162 T49951 Hs 9029 DKFZP434G032 protein 237
418583 AA604379 Hs 86211 hypothetical protein 237
417008 AA191708 Hs 325825 Homo sapiens cDNA FLJ20848 fis, clone AD 237
459057 AW005512 ESTs, Weakly simllarto A61262 collagen 237
447120 AI380413 Hs 233297 ESTs 237
427712 A1368024 Hs 283696 ESTs 237
435099 AC004770 Hs 4756 flap structure-specific endoπuciease 1 237
421878 AA299652 Hs 111496 Homo sapiens cDNA FLJ11643 fis, clone HE 237
434614 AI249502 Hs 29669 ESTs 237
413437 BE313164 Hs 75361 gene from NF2/mentngIoma region of 22q12 237
428821 H91282 Hs 286232 Homo sapiens cDNA FLJ23190 fis, clone L 236
419897 X90826 Hs 93649 upstream transcnpton factor 2, c fos I 236
437016 AU076916 Hs 5398 guanine monphosphate synthetase 236
421011 BE300408 Hs 119699 hypothetical protein FLJ 12969 236
409407 AW967370 Hs 342655 Homo sapiens cDNA FLJ13289 fis, clone OV 236
415204 T27434 gb hbc2294 Human pancreatic Islet Homo s 236
449162 AI632740 Hs 10476 ESTs 236
429238 NM 002849 Hs 198288 protein tyrosine phosphatase, receptor t 236
449955 AI676010 Hs 224043 ESTs 236
449791 AI248740 Hs 133323 ESTs 236
422515 AW500470 Hs 117950 multifunctional polypeptide similar to S 236
419102 AA234098 Hs 42424 ESTs, Weakly simllarto 2004399A chromos 236
411734 AW374954 Hs 71779 Homo sapiens DNAfrom chromosome 19, cos 236
405723 Target Exon 236
456623 AI084125 Hs 108106 transcnpton factor 236
442013 AA506476 Hs 82689 Human DNA sequence from clone RP11-353C1 236
429770 AI766047 Hs 99736 ESTs 236
407317 AI204033 Hs 30792 ESTs, Weakly slmilarto I38022 hypothet 235
421910 NM.014586 Hs 109437 hormonally upregulated neu tumor-associa 235
404120 C5000537* gi|3298595|gb|AAC41376 1| (AF0 235
452483 AI903731 Hs 106357 valosin containing protein 235
435755 AA805263 Hs 123176 ESTs 235
428550 AW297880 Hs 98661 ESTs 235
449158 AI990849 ESTs 235
449256 AA059050 Hs 59847 ESTs 235
442617 AW340093 Hs 130538 ESTs 235
459557 N58315 gb yv68g06 s1 Soares fetal liver spleen 235
425363 BE161577 Hs 10119 hypothetical protein FLJ 14957 235
448030 N30714 Hs 325960 membrane spanning 4-domaιπs, subfamily A 235
437159 AL050072 Hs 306313 Homo sapiens mRNA, cDNA DKFZp566E1346 (f 235
440462 T71629 Hs 100554 ESTs 235
458375 A1885827 Hs 7149 ESTs, Weakly slmilarto T13963 formin re 235
454645 AW811928 gb RC2 ST0168 240300 017 b02 ST0168 Homo 235
435126 AI393666 Hs 42315 p10 binding protein 235
411226 AW833022 gb RC3 TT0005 191099-012 d04 TT0005 Homo 235
402285 sclerostin 235
423805 AA331242 Hs 197030 gb EST35320 Embryo, 8 week I Homo sapien 235
446338 AI289121 Hs 206978 ESTs 235
400817 Target Exon 235
459507 AW298279 Hs 255756 ESTs 235
425368 AB014595 Hs 155976 cullln 4B 235
425212 AW962253 Hs 171618 ESTs 235
426098 NM 014906 Hs 166351 KIAA1072 protein 235
457653 AI820719 Hs 76853 DnaJ (Hsp40) homolog, subfamily A membe 235
432281 AK001239 Hs 274263 hypothetical protein FLJ10377 235
418592 X99226 Hs 284153 Fanconl anemia complementation group A 235
402505 C1003830 gi|3983382|gb|AAD13319 1| (AF10 235
410415 BE241626 Hs 285833 Homo sapiens cDNA FLJ22135 fis, clone H 235
418216 AA662240 Hs 283099 AF15q14 protein 235
459200 Y09306 Hs 30148 homeodomaln Interacting protein kinase 3 235
413320 NM.005191 Hs 838 CD80 antigen (CD28 antgen ligand 1, B7- 235
430084 AA748878 Hs 281764 ESTs 235
412043 BE156622 Hs 333371 Homo sapiens clone TA40 untranslated mRN 235
446651 AA393907 Hs 97179 ESTs 235
431696 AA259068 Hs 267819 protein phosphatase 1, regulatory (Inhlb 235
451065 AW295132 Hs 222231 ESTs, Weakly simllarto granule cell mar 235
451232 AI769922 Hs 20023 ESTs 235
416018 AW138239 Hs 78977 proproteiπ convertase subtilisin/kexln t 235
448762 H19006 Hs 184780 ESTs 235
432226 AW182766 Hs 273558 phosphate cytdylyltransterase 1, cholln 235
435062 BE501995 Hs 282228 ESTs 235
417239 AA854504 Hs 85956 ESTs Weakly similar to B28096 llπe-1 pr 235
450724 R55428 gb yj79b05 r1 Soares breast 2NbHBst Homo 235
425048 H05468 Hs 164502 ESTs 235 453455 AA063553 Hs.221931 ESTs, Weakly similar to JC1087 RNA hellc 2.35
434874 N62448 Hs.293970 methylmalonate-semialdehyde dehydrogenas 2.35
409187 AF154830 Hs.50966 carbamoyl-phosphate synthetase 1, mitoch 2.35
444261 AA298958 Hs.10724 MDS023 protein 2.35
414205 BE382438 Homo sapiens, clone IMAGE:3690478, mRNA, 2.35
428862 NM 000346 Hs.2316 SRY (sex determining region Y)-box 9 (ca 2.35
448633 AA311426 Hs.21635 tubulin, gamma 1 2.35
418758 AW959311 Hs.172012 hypothetical protein DKFZp434J037 2.35
420783 AI659838 Hs.99923 lectin, galactoslde-binding, soluble, 7 2.35
439866 AA280717 Hs.6727 Ras-GTPase activating protein SH3 domain 2.35
454003 AA058944 Hs.116602 Homo sapiens, clone IMAGE:4154008, mRNA, 2.34
458B66 BE616694 Hs.288042 hypothetical protein FLJ14299 2.34
425532 AB007915 Hs.158286 KIAA0446 gene product 2.34
436420 AA443966 Hs.31595 ESTs 2.34
420542 NM.000505 Hs.1321 coagulation factor XII (Hageman factor) 2.34
417389 BE260964 Hs.82045 midkine (πeurite growth-promoting factor 2.34
407704 BE315072 Hs.78768 malignant cell expression-enhanced gene/ 2.34
421649 AA721217 Hs.106415 peroxlsome proliferatve activated recep 2.34
424042 Y10601 Hs.137674 ankyrin-like with transmembrane domains 2.34
414883 AA926960 CDC28 protein kinase 1 2.34
414270 L20852 Hs.347527 solute carrierfamlly 20 (phosphate tran 2.34
428698 AA852773 Hs.334838 KIAA1866 protein 2.34
410170 AI700481 Hs.299629 peroxlsomal long-chain acyl-coA thloeste 2.34
422567 AF111178 Hs.118407 glypican 6 2.34
418418 R61527 Hs.237517 ESTs 2.34
407661 AW063497 Hs.279821 ESTs 2.33
450088 AW292933 Hs.254110 ESTs 2.33
427279 AW971391 Hs.28113 ESTs, Weakly slmilarto KIAA0349 [H.sapl 2.33
417133 N49848 Hs.104091 ESTs 2.33
419457 AA243146 Hs.209334 ESTs, Moderately similar to S23A.HUMAN P 2.33
405215 Target Exon 2.33
449186 AW291876 Hs.196986 ESTs 2.33
445929 AI089660 Hs.323401 dpy-30-like protein 2.33
425265 BE245297 gb:TCBAP1E2482 Pediatric pre-B cell acut 2.33
402008 Target Exon 2.33
449207 AL044222 Hs.23255 nucleoporin 155kD 2.33
432842 AW674093 Hs.334822 hypothetical protein MGC4485 2.33
420089 AW003785 Hs.170267 ESTs 2.33
447966 AA340605 Hs.105887 ESTs, Weakly similar to Homolog of rat Z 2.33
418951 F07809 Hs.89506 paired box gene 6 (aniridia, keratits) 2.33
405387 NM_022170*:Homo sapiens Williams-Beuren 2.33
412124 H43378 Homo sapiens cDNA: FLJ23156 fis, clone L 2.33
417018 M16038 Hs.80887 v-yes-1 Yamaguchl sarcoma viral related 2.33
405573 Target Exon 2.32
422253 W81526 Hs.118329 ESTs, Moderately similar to GAD.HUMAN GA 2.32
422363 T55979 Hs.115474 replication factor C (activator 1) 3 (38 2.32
413952 AA806187 Hs.289101 glucose regulated protein, 58kD 2.32
407649 BE066724 Hs.37427 erythrocyte membrane protein band 4.1 (e 2.32
413492 D87470 Hs.75400 KIAA0280 protein 2.32
413753 U17760 Hs.75517 laminln, beta 3 (nlceln (125kD), kalinin 2.32
446506 AI123118 Hs.15159 chemokine-like factor, alternatively spl 2.32
444734 NM 001360 Hs.11806 7-dehydrocholesterol reductase 2.32
437210 AA3~H443 Hs.293563 Homo sapiens mRNA; cDNA DKFZp586E2317 (f 2.32
407027 U63312 gb:Human cosmld LL12NC01-242E1, ETV6 gen 2.31
407252 AA659037 Hs.163780 ESTs 2.31
408075 AA382881 Hs.42409 CGI-146 protein 2.31
452767 AW014195 Hs.61472 ESTs, Weakly slmilarto YAE6.YEAST HYPOT 2.31
426516 BE262660 Hs.170197 glutamic-oxaloacetc transamlnase 2, mit 2.31
423864 BE275607 Hs.1708 chaperonln containing TCP1, subunlt 3 (g 2.31
402663 C1002133:gi|12697931|dbj|BAB21784.1| (AB 2.31
452482 BE155356 gb:PM1-HT0350-160300-009-d06 HT0350 Homo 2.31
419535 AW139550 Hs.115173 ESTs 2.31
446335 BE174202 Hs.156067 Homo sapiens cDNA: FLJ21061 fis, clone C 2.31
420552 AK000492 Hs.98806 hypothetical protein 2.31
457461 AL122087 Hs.272304 Homo sapiens mRNA; cDNA DKFZp564C0371 (f 2.31
401917 RAN binding protein 3 2.31
427678 BE267756 Hs.180312 mltochondrial ribosomal protein S16 2.31
429857 AF089897 Hs.294030 topolsomerase-related function protein 4 2.30
437613 R19892 Hs.10267 MIL1 protein 2.30
429162 AK001250 Hs.197642 hypothetical protein FLJ10388 2.30
427051 BE178110 Hs.173374 Homo sapiens cDNA FLJ10500 fis, clone NT 2.30
432407 AA221036 Hs.13273 gb;zr03f12.r1 Stratagene NT2 neuronal pr 2.30
415099 AI492170 Hs.77917 ublqultln carboxyl-termlnal esterase L3 2.30
432543 AA552690 Hs.152423 Homo sapiens cDNA: FLJ21274 fis, clone C 2.30
446237 AW270515 Hs.149596 Homo sapiens, Simllarto RIKEN cDNA 2310 2.30
436668 AA831857 Hs.209071 ESTs 2.30
452146 AW135654 p47 2.30
404494 C8001441*;gl|8923061|ref|NP_060114.1| hy 2.30
426262 AI792141 Hs.196270 folate transporter/carrier 2.30
439019 AF085902 Hs.271737 ESTs 2.30
400639 C10000999*:gl|2143593|plri|S55277 annexl 2.30
454204 AW816498 gb:QV0-ST0236-171299-075-b02 ST0236 Homo 2.30
424194 BE245833 Hs.169854 gb;TCBAP1E1908 Pediatric pre-B cell acut 2.30
421093 AA906434 Hs.3776 zinc finger protein 216 2.30
435276 AI022399 Hs.186934 ESTs 2.30
451084 N30113 Hs.299014 ESTs 2.30 409078 AW327515 ESTs 230
412661 N32860 Hs 24611 ESTs, Weakly similar to I54374 gene NF2 230
418150 AA973762 Hs 22222 hypothetical protein MGC10854 230
411688 AW953440 gb EST365510 MAGE resequences, MAGB Homo 230
437863 AA769989 ESTs, Moderately similar to ZN91.HUMAN Z 230
445523 Z30118 Hs 293788 ESTs, Moderately similar to unnamed prat 230
421674 T10707 Hs 296355 hypothetical protein FLJ23138 230
405705 C12000104*gi|4503519|ref|NP_003745 1| e 230
409872 AW502313 gbUI HF BR0p-a]s-d 08 0 Ul r1 NIH.MGC.5 230
440612 BE561384 gb 601344969F1 NIH.MGC.8 Homo sapiens cD 230
422408 AI340322 Hs 156928 Homo sapiens cDNA FLJ21942 fis, clone H 230
429433 AA452899 Hs 213586 ESTs, Weakly similar to KIAA1353 protein 230
406930 U04691 gb Human olfactory receptor (OR17-219) g 230
448472 BE612556 Hs 47783 B aggressive lymphoma gene 230
419852 AW503756 Hs 286184 hypothetical protein dJ551D25 230
440097 AI079949 Hs 134192 ESTs 230
455540 BE080231 gb RC4 BT0629-120200 012f11 BT0629 Homo 230
424316 AA676403 Hs 145078 regulatorof differentiation (in S pomb 230
404423 C8000067* gi|10432400|emb]CAC10290 1| (A 230
427548 AA813784 Hs 123001 ESTs 230
438171 AW976507 ESTs 230
431611 U58766 Hs 264428 tissue specific transplantation antgen 230
440100 BE382685 Hs 158549 ESTs, Weakly slmilarto T2D3.HUMAN TRANS 230
417750 AI267720 Hs 260523 synovial sarcoma, translocated to Xchro 230
426088 AF038007 Hs 166196 ATPase, Class I, type 8B, member 1 230
414485 W27026 Hs 182625 VAMP (vesicle associated membrane protei 230
411007 AA311529 Hs 67619 hypothetical protein My014 230
410512 AA085603 Hs 250570 hypothetical protein MGC3180 230
426427 M86699 Hs 169840 TTK protein kinase 230
437897 AA770561 Hs 146170 hypothetical protein FLJ22969 230
431462 AW583672 Hs 256311 granin like neuroendocπne peptde precu 230
458820 BE552151 Hs 108118 hypothetical protein FLJ22474 230
422678 AA247778 Hs 119155 Homo sapiens mRNA full length insert cDN 230
430640 AA482636 Hs 209561 KIAA1715 protein 230
428157 AI738719 Hs 198427 hexoklnase 2 230
443015 R33261 Hs 6614 ESTs, Weakly slmilarto A43932 mucin 2 p 230
426860 U04953 Hs 172801 isoleucine tRNA synthetase 229
437150 R51407 Hs 77910 3 hydroxy 3 methylglutaryl Coenzyme A sy 229
401913 ENSP00000249158* CDNA 229
442592 BE566623 Hs 29899 ESTs, Weakly simllarto G02075 transcπp 229
446038 AW162917 Hs 321635 gb au90d03 y1 Schneider fetal brain 0000 229
416820 NM 000402 Hs 80206 glucose 6 phosphate dehydrogenase 229
421535 AB002359 Hs 105478 phosphonbosylformylglyclnamldlne syntha 229
446567 NM.007247 Hs 15384 AP1 gamma subuπit binding protein 1 229
451134 AA318315 Hs 25999 hypothetical protein FLJ22195 229
441659 BE564162 Hs 250820 hypothetical protein FLJ14827 229
434182 W20309 Hs 118520 G protein gamma 12 subunlt 229
447118 AB014599 Hs 330988 Homo sapiens, Slmilarto Bicaudal D (Dro 229
443044 N28522 Hs 8935 quinolinate phosphonbosyltransferase (n 229
405028 C9001589 gι|548751|sp|P36241|RL19_DROME 229
418747 AJ249977 Hs 88049 protein kinase, AMP activated gamma 3 n 229
402189 ENSP00000247423* D-siglec precursor 229
408743 AL110246 Hs 47367 KIAA1785 protein 229
408697 AW419069 Hs 209670 ESTs 229
408249 AW271838 Hs 44038 pellino (Drosophila) homolog 2 229
432279 N95104 Hs 274260 ATP binding cassette, sub family C (CFTR 228
446229 AI744964 Hs 14449 KIAA1609 protein 228
421828 AW891965 hlstone deacetylase 3 228
451351 AW058261 Hs 321435 ESTs, Weakly simllarto ALU1.HUMAN ALU S 228
412445 X51362 Hs 73893 dopamine receptor D2 228
425671 AF193612 Hs 159142 lunate fππge (Drosophila) homolog 228
425360 BE547704 Hs 15276 gb 601076309F1 NIH MGC 12 Homo sapiens c 228
454560 AW807281 gb MR4 ST0062240300 003 g01 ST0062 Homo 228
430016 NM 004736 Hs 227656 xenotroplc and polytropic retrovlrus rec 228
457234 AW968360 Hs 14355 Homo sapiens cDNA FLJ13207 fis, clone NT 228
458132 AW247012 Hs 103267 hypothetical protein FLJ22548 simllarto 228
432871 NM 016142 Hs 279617 steroid dehydrogenase homolog 228
409119 AA531133 Hs 4253 hypothetical protein MGC2574 227
452700 AI859390 Hs 288940 five span transmembrane protein M83 227
400414 AF083118 Hs 283968 Homo sapiens CATX-2 mRNA complete eds 227
401804 C17000304* gi|9801259|emb|CAC03558 1| (A 227
428599 AB033078 Hs 186613 sphlngoslne 1 phosphate lyase 1 227
409465 AW393810 Hs 78054 gb QV4-TT0008-251099016 e11 TT0008 Homo 227
434067 H18913 Hs 124023 Homo sapiens cDNA FLJ14218 fis, clone NT 227
447656 NM 003726 Hs 19126 src kinase associated phosphoprotein of 227
448641 R31845 Hs 21666 Insulin like 4 (placenta) 227
409442 AA310162 Hs 169248 cytochrome c 227
409213 U61412 Hs 51133 PTK6 protein tyrosine kinase 6 227
411942 AW877015 gb QV2 PT0010250300 096 f12 PT0010Homo 227
415279 F04237 Hs 1447 gllal fibnllary acidic protein 227
448667 Z78394 Hε 4896 Homo sapiens cDNA FLJ22046 fis, clone H 227
409714 AW367812 Hs 199961 ESTs, Weakly slmilarto ALU7.HUMAN ALU S 227
444984 H15474 Hs 132898 fatty add desaturase 1 227
411737 AW160339 Hs 71791 hypothetical protein 227
428054 AI948688 Hs 266619 ESTs 226
407844 AW073716 HS 8037 ESTs 226 447484 AA464839 Hs 292566 hypothetical protein FLJ14697 226
442723 AI804331 Hs 99423 ATP dependent RNA helicase 226
433626 AF078859 Hs 86347 hypothetical protein 226
425960 AW410646 Hs 164649 hypothetical protein DKFZp434H247 226
456258 AW976410 Hs 289069 Homo sapiens clone FLB3411 PRO0852 mRNA, 226
408482 NM 000676 Hs 45743 adenosine A2b receptor 226
427752 AA470687 Hs 104772 ESTs 226
444572 R50145 Hs 270549 HZFwl protein 226
422010 AA302049 HS 31181 Homo sapiens cDNA FLJ23230 fis, clone C 226
433698 H24201 Hs 247423 adducln 2 (beta) 226
416636 N32536 Hs 42645 solute earner family 16 (monocarboxylic 226
422248 AL109695 Hs 113657 Homo sapiens mRNA full length Insert cDN 226
431604 AF175265 Hs 264190 vacuolar protein sorting 35 (yeast homol 226
447211 AL161961 Hs 17767 KIAA1554 protein 225
414906 AA157911 Hs 72200 ESTs 225
450746 D82673 Hs 278589 general transcπpton factor II, I 225
412326 R07566 Hs 73817 small inducible cytokine A3 (homologous 225
422955 AW967824 Hs 324237 ESTs 225
448918 AB011152 Hs 22572 KIAA0580 protein 225
402229 mltochondπal πbosomal protein S2 225
446550 AW500453 Hs 34455 gbUl-HF-BNO akb c-11-O-UI r1 NIH.MGC.50 225
425702 N59555 gb yv76f05 s1 Soares fetal liver spleen 225
416707 H78163 Hs 14005 ESTs 225
450754 AW204237 ESTs, Weakly slmilarto ALU1 HUMAN ALU S 225
428898 AB033070 Hs 194408 KIAA1244 protein 225
404877 NM.005365 Homo sapiens melanoma antigen, 225
441926 AI015051 Hs 130953 ESTs 225
424003 BE274717 Hs 137506 Homo sapiens, clone IMAGE 3605104, mRNA, 225
411782 H30518 gb yp41 b03 s1 Soares retina N2b5HR Homo 225
443741 AW451759 Hs 145420 ESTs 225
404341 Target Exon 225
438632 AI910521 Hs 123493 ESTs 225
442481 N99828 gb za32c04 Soares fetal liver spleen 225
401160 Target Exon 225
413940 AI633205 Hs 159914 ESTs, Weakly simllarto I78885 seππe/th 225
401925 slalyltransferase 1 (beta-galactoside al 225
410401 AW673335 Hs 259641 ESTs 225
418764 N30531 Hs 42215 protein phosphatase 1, regulatory subuni 225
407687 AK002011 Hs 37558 hypothetical protein FLJ 11149 225
449065 AI627393 Hs 258998 ESTs, Weakly slmilarto high mobility gr 225
452243 AL355715 Hs 28555 programmed cell death 9 (PDCD9) 225
417124 BE122762 Hs 25338 ESTs 225
432821 BE170702 Hs 279005 solute earner family 21 (organic anion 225
425416 AK000909 Hs 157103 hypothetical protein FLJ12644 225
446182 AV656995 Hs 269904 ESTs 225
428180 AI129767 Hs 182874 guanine nucleotide binding protein (G pr 225
422285 AI803103 gb tc14e06 x1 Soares NhHMPu S1 Homo εapi 225
444326 AI939357 ESTs 225
446147 AL133064 Hs 14051 Homo sapiens mRNA, cDNA DKFZp434A2417 (f 225
432808 NM 015985 Hs 278973 angιopoletn-3 225
434639 R83159 Hs 33366 EST 225
442430 R89164 double nπg finger protein, Dorfin 225
406374 C16001364 gi|11067373|ref|NP_067689 1| C 225
428405 Y00762 Hs 2266 cholinerglc receptor, nicotnlc, alpha p 225
428466 AF151063 Hs 184456 hypothetical protein 225
417046 AA192639 gb zq01h09 r1 Stratagene muscle 937209 H 225
439239 AI031540 Hs 235331 ESTs 225
431820 AW410408 Hs 271167 L-pipecollc add oxldase 225
413273 U75679 Hs 75257 stem loop (hlstone) binding protein 225
400234 NM.005336 Homo sapiens high density lipo 225
413691 AB023173 Hs 75478 ATPase, Class VI, type 11B 225
436856 AI469355 Hs 127310 ESTs 225
424685 W21223 Hs 151734 nuclear transport factor 2 (placental pr 225
435438 H84421 Hs 4890 ublquitn conjugating enzyme E2E 3 (homo 225
440043 BE277457 Hs 30661 hypothetical protein MGC4606 225
453575 AB023211 Hs 33455 peptidyl arglnlne delminase, type II 224
424689 D43947 Hs 151761 KIAA0100 gene product 224
428206 AB020643 Hs 183006 KIAA0836 protein 224
417207 N92226 Hs 338218 ESTs 224
430979 AI479755 Hs 129010 ESTs 224
402530 Target Exon 224
427691 AW194426 Hs 20726 UDP-N acetyl alpha D-galactosamlne polyp 224
434206 AW136973 ESTs, Weakly simllarto S69890 mltogen I 224
452017 AF109302 Hs 27495 prostate cancer associated protein 7 224
422127 AW504286 Hs 112049 SET binding factor 1 224
408949 AF189011 Hs 49163 putative dbonuclease III 224
441085 AW136551 Hs 181245 Homo sapiens cDNA FLJ12532 fis, clone NT 224
425140 AB014567 Hs 154740 TBP Interactng protein 224
423840 AA332434 Hs 72465 ESTs, Weakly similar to non-lens beta ga 224
420428 AA262050 Hs 156148 hypothetical protein FLJ13231 224
448497 BE613269 Hs 21893 hypothetical protein DKFZp761N0624 224
411400 AA311919 Hs 69851 nucleolar protein family A, member 1 (HI 223
431683 AK001749 Hs 267604 hypothetical protein FLJ 10450 223
421222 AA306049 Hs 102669 DKFZP4340125 protein 223
425118 AU076611 Hs 154672 methylene tetrahydrofolate dehydrogenase 223
447948 AI620923 Hs 46679 hypothetical protein FLJ20739 223 403332 Target Exon 223
431123 X77723 Hs 326056 rabaptn-5 223
421247 BE391727 Hs 102910 general transcπpton factor IIH, polype 223
421568 W85858 Hs 99804 ESTs 223
458376 AB023179 Hs 9059 KIAA0962 protein 223
452388 BE019696 Hs 29287 retnoblastoma binding protein 8 223
401952 Target Exon 223
402819 ENSP00000235150 DJ1174N9 1 (novel protei 223
437582 AW673321 Hs 46903 hypothetical protein FLJ12838 223
439180 AI393742 Hs 199067 v-erb-b2 avlan erythroblastc leukemia v 222
409960 BE261944 hexokinase 1 222
451617 C01056 hypothetical protein FLJ12577 222
435956 AF269255 Hs 22604 lysosomal apyrase-like protein 1 222
431863 AA188185 Hs 289043 splndlm 222
409456 U34962 Hs 54473 cardiac-specific homeo box 222
425354 U62027 Hs 155935 complement component 3a receptor 1 222
445664 AW968638 Hs 237691 ESTs, Weakly similar to KIAA0601 protein 222
453915 AA588721 Hs 286218 nbosomal protein L44 222
431896 AW297844 Hs 101428 ESTs 222
429377 AA813192 Hs 200596 KIAA0547 gene product 222
409189 AA125984 gb zn27h06 r1 Stratagene neuroepithellum 222
452488 N74921 Hs 184389 ESTs 222
445356 AW304777 Hs 249690 ESTs 222
402014 Target Exon 222
420014 AI248571 Hs 13913 KIAA1577 protein 222
455618 BE155563 gb PM4-HT0352-171199 001-C05 HT0352 Homo 221
437063 AA351109 Taxi (human T-cell leukemia vims type I 221
419508 AW997938 Hs 90786 ATP-blndlng cassette, sub-family C (CFTR 221
409185 AW961601 Hs 252406 hypothetical protein FLJ 12296 slmilarto 221
456999 AA319798 Hs 298581 eukaryotic translation elongation factor 221
400203 Eos Control 221
412490 AW803564 Hs 288850 Homo sapiens cDNA FLJ22528 fis, clone H 221
434878 AW975086 gb EST387192 MAGE resequences, MAGN Homo 221
429898 AW117322 Hs 42366 ESTs 221
444784 D12485 Hs 11951 ectonucleotde pyrophosphatase/phosphodi 221
447197 R36075 gb yh88b01 s1 Soares placenta Nb2HP Homo 221
417691 AU076610 Hs 82399 low density lipoproteln receptor defect 221
449949 AI675753 Hs 186530 ESTs, Weakly slmilarto S65657 alpha-1C- 221
410553 AW016824 Hs 272068 hypothetical protein MGC14128 221
421551 AF063539 Hs 97300 ESTs 221
414600 NM.005647 Hs 76536 transducin (beta)-lιke 1 221
428726 AA432195 Hs 98694 ESTs 220
452753 AA028049 Hs 277728 SEC14 (S cerevisιae)-like 2 220
434916 AF161383 Hs 284207 Homo sapiens, Similar to RIKEN cDNA 1110 220
408113 T82427 Hs 194101 Homo sapiens cDNA FLJ20869 fis, clone A 220
428385 AF112213 Hs 184062 putative Rab5 Interacting protein 220
459376 BE258770 Homo sapiens, clone IMAGE 3344506, mRNA, 220
455475 AW948126 gb RC0- T0013-280300-031 -a12 MT0013 Homo 220
403549 ENSP00000187471 HSNFRK 220
434356 AW467161 Hs 78563 ubiquitin-conjugatng enzyme E2G 1 (homo 220
445292 AV653264 Hs 13982 Homo sapiens cDNA FLJ14666 fis, clone NT 220
403481 Target Exon 220
410101 AI338045 Hs 203559 hypothetical protein FLJ12701 220
401438 ENSP00000238580* SIMILARITY IS TO THE EN 220
421642 AF172066 Hs 106346 retinolc acid represslble protein 220
403429 C3000329* gi|8922921|ref|NP_060821 1| hy 220
440129 AA865818 ESTs, Weakly similar to S71886 Ste20 Ilk 220
414571 BE410746 Hs 22868 protein tyrosine phosphatase, πoπ-recept 220
451859 H44491 Hs 252938 ESTs, Weakly slmilarto ALU1 HUMAN ALU S 220
410859 AW807604 gb MR4-ST0098-120100-001-b02 ST0098 Homo 220
403154 NM 022780* Homo sapiens hypothetical pro 220
447054 AW086454 Hs 169248 ESTs 220
443108 W86975 ESTs 220
450058 AW452752 Hs 256034 ESTs 220
410434 AF051152 Hs 63668 toll-like receptor 2 220
411436 AW846433 gb QV0-CT0179-070300-143-b02 CT0179 Homo 220
414898 AA157726 Hs 264330 N-acylsphlngosine amidohydrolase (acid c 220
448501 AA332316 hypothetical protein FLJ13159 220
457378 AW972118 Hs 100002 HSPC162 protein 220
422890 Z43784 aπkyrin 3, node of Ranvler (ankynn G) 220
438814 AA826278 ESTs 220
425810 AI923627 Hs 31903 ESTs 220
436683 AW991278 Hs 57787 ESTs 220
410465 AW963279 Hs 123373 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 220
433597 AA708205 Hs 100343 ESTs 220
437838 AI307229 ESTs 220
403858 Target Exon 220
445325 AF052115 Hs 12514 Homo sapiens clone 23688 mRNA sequence 220
450750 H83398 Hs 40489 ESTs 220
417173 U61397 Hs 81424 ublquitin-like 1 (sentrln) 220
437587 AI591222 Hs 72325 Human DNA sequence from clone RP1-187J11 220
423020 AA383092 Hs 1608 replication protein A3 (14kD) 220
429904 AL080077 Hs 225997 Homo sapiens mRNA, cDNA DKFZp564C0962 (f 220
421387 AF059566 Hs 103983 solute carrierfamlly 5 (sodium Iodide s 220
429626 U36787 Hs 211571 holocytochrome c synthase (cytochrome c 220
411911 AW875951 gb CM1-PT0013-131299-067-f09 PT0013 Homo 220 438093 BE206885 Hs 6076 C0P9 (constitutive photomorphogenlc, Ara 220
432262 AW197269 Hs 127240 hypothetical protein FLJ10211 220
414178 AW957372 Hs 46791 ESTs, Weakly simllarto I38022 hypothet 219
424766 BE388855 Hs 152978 proteaseome (prosome, macropaln) 28 subu 219
455299 AW891612 gb CM3 NT0089 040500-174 a04 NT0089 Homo 219
422416 BE019557 Hs 11900 hypothetical protein FLJ14972 219
428758 AA433988 Hs 98502 CA125 antigen, muciπ lδ 219
410600 AW575742 ESTs, Moderately similar to S65657 alpha 219
400540 Target Exon 219
445176 AI878907 Hs 12379 ELAV (embryonic lethal, abnormal vision, 219
445350 AF052112 Hs 12540 lysophospholipase I 219
420718 NM.002301 Hs 99881 lactate dehydrogenase C 219
436605 Al 187742 Hs 125562 ESTs 219
421353 AW292857 Hs 255130 ESTs 219
435080 AI831760 Hs 155111 hypothetical protein FLJ14428 219
419252 AW138434 Hs 129805 ESTs 219
419591 AF09O90O Hs 91393 Homo sapiens cDNA FLJ21887fis clone H 219
410687 U24389 Hs 65436 lysyl oxldase like 1 219
446849 AU076617 Hs 16251 cleavage and polyadenylaton specific fa 219
414740 R61532 Hs 87016 hypothetical protein FLJ22938 219
432707 AW604865 Hs 158515 hypothetical protein MGC13038 219
448362 AA641767 Hs 21015 hypothetical protein DKFZp564L0864 slmil 219
430637 BE160081 Hs 256290 S100 calcium binding protein A11 (calgiz 219
432348 AA534353 Hs 194081 ESTs, Weakly slmilarto I38022 hypothet 219
419444 NM.002496 Hs 90443 Target CAT 2 19
401403 Target Exon 219
432621 AI298501 Hs 21192 ESTs Weakly simllarto T46428 hypothet 219
428281 AA194554 Hs 183434 ATPase, H transporting Iysosomal (vacuo 218
421525 AW977559 Hs 4193 DKFZP58601624 protein 218
433139 AB029826 Hs 47649 methylcrotonoyl Coenzyme A carboxylase 1 218
444298 Z17870 gb HSDHII020 Stratagene cDNA library Hum 218
428074 BE387770 Hs 182378 colony simulating factor 2 receptor, al 218
406423 C19000229* gl|6753826|ref|NP_034311 1| f 218
442911 AI023895 Hs 190587 ESTs 218
425524 AB007866 Hs 158249 KIAA0406 gene product 218
413063 AL035737 Hs 75184 chltlnase 3 like 1 (cartilage glycoprote 218
450998 BE387614 Hs 25797 splicing factor 3b, subunlt 4, 49kD 218
440035 BE561589 hypothetical protein FLJ21839 218
451025 AW028689 Hs 301985 ESTs 218
449008 AW578003 Hs 22826 tropomodulin 3 (ubiquitous) 218
426174 AA547959 Hs 115838 Homo sapiens similar to Echinoidin (LOC1 2 18
416322 BE019494 Hs 79217 pyrroline 5 carboxylate reductase 1 2 17
401711 C16000267 gιl6330617|db]|BAA865371| (AB 2 17
446989 AK001898 Hs 16740 hypothetical protein FLJ 11036 217
416375 H95567 Hs 124700 ESTs 217
453985 N44545 Hs 251865 ESTs 217
402942 Target Exon 217
400120 Eos Control 217
401138 Target Exon 217
414108 AI267592 Hs 75761 SFRS protein kinase 1 217
427715 BE245274 Hs 180428 KIAA1181 protein 217
448407 AI498957 Hs 170861 ESTs, Weakly slmilarto Z195.HUMAN ZINC 217
448745 H51548 Hs 21899 solute earner family 35 (UDP galactose 217
436265 AA731331 Hs 190668 ESTs 217
406237 Target Exon 217
402322 Target Exon 217
416812 H91010 Hs 44940 ESTs 217
429462 AI890356 Homo sapiens clone IMAGE 3536432, mRNA, 217
438098 AI076370 Hs 134037 ESTs 217
442134 BE552359 Hs 225092 ESTs 2 17
445922 Al 337316 Hs 147998 ESTs 2 17
419590 AF005043 Hs 91390 poly (ADP-πbose) glycohydrolase 2 17
446290 AW769683 Hs 6734 ESTs, Weakly slmilarto S26650 DNA blndi 2 17
413313 NM.002047 Hs 283108 glycyl tRNA synthetase 2 17
404661 C9000306* gi|12737280|ref|XP_0066822\ k 217
448854 AW245617 Hs 77703 hypothetical protein FLJ 11506 216
414169 AA136169 Hs 149335 ESTs 216
414161 AA136106 Hs 184852 KIAA1553 protein 216
445070 NM 000677 Hs 258 adenoslne A3 receptor 216
446830 BE179030 Human DNA sequence from clone RP5-1174N9 216
414636 AL120259 Hs 76691 stannln 216
432626 AA471098 Hs 278544 acetyl Coenzyme A acetyltransferase 2 (a 216
428582 BE336699 Hs 185055 BENE protein 216
453710 AL119136 Hs 236131 homeodomain Interacting protein kinase 2 216
438510 AL080220 Hs 6285 DKFZP586P0123 protein 2 16
454034 NM 000691 HS 575 aldehyde dehydrogenase 3 family, member 2 16
451991 AA768353 Hs 163709 ESTs, Moderately similar to I38022 hypot 2 16
415282 R44308 Hs 242302 ESTs 216
415443 T07353 Hs 7948 ESTs 216
409267 NM 012453 Hs 52515 transducin (beta) like 2 216
440300 N39760 Hs 8859 Homo sapiens, Similar to RIKEN cDNA 5830 216
440494 BE618768 HS 7232 acetyl Coenzyme A carboxylase alpha 216
435550 AI224456 Hs 324507 H sapiens polyA site DNA 216
415914 AA306033 Hs 78915 GA-binding protein transcription factor, 216
436700 AI693690 Hs 301406 hypothetical protein PP3501 215
454150 AA131893 Hs 154088 hypothetical protein FLJ22756 215 423540 AI038192 Hs 95361 EGF like repeats and discoldln I like do 215
400084 Eos Control 215
453129 R35265 Hs 237946 ESTs, Weakly slmilarto TRHY.HUMAN TRICH 215
421861 S78798 Hs 108966 phosphatdylinosιtol-4-phosphate 5 kinas 215
421506 BE302796 Hs 105097 thymldine kinase 1, soluble 215
405673 NM 022775 Homo sapiens hypothetcal prot 215
413774 AA131782 Hs 182314 ESTs 215
452177 AI863447 Hs 268180 gb tz48f01 x1 NCI.CGAP Brn52 Homo sapien 2 15
450166 AA429504 Hs 8765 ESTs 215
425094 AI955956 Hs 21417 ESTs 215
453265 U61232 Hs 343564 tubulln specific chaperone e 215
445255 NM.014841 Hs 12477 synaptosomal associated protein, 91 kDa 215
400125 Eos Control 215
456806 AI222298 Hs 140720 GSK-3 binding protein FRAT2 215
447497 AW167254 Hs 205722 ESTs 215
405869 Target Exon 215
406261 Target Exon 215
413286 AA127984 Hs 222024 transcπpton factor BMAL2 215
446457 AI300580 ESTs Moderately similar to ALU1 HUMAN A 215
437054 AA743376 Hs 120592 ESTs 215
401708 Target Exon 215
417185 NM.002484 Hs 81469 nucleotide binding protein 1 (E coli Mm 215
402704 C1001099* gι|6005896|ref|NP_009101 1| te 215
454923 AW897236 gb CMO NN0057-150400 335 c06 NN0057 Homo 2 15
431231 AA653552 Hs 116532 ESTs 215
447229 BE617135 Hs 22612 hypothetical protein DKFZp566D1346 215
416554 H72721 Hs 203509 ESTs, Weakly similar to I38022 hypothet 215
431316 AA502663 Hs 145037 ESTs 215
414727 BE466904 Hs 190162 gb hz28f03 x1 NCI.CGAP.GC6 Homo sapiens 215
410307 AF022913 Hs 62187 phosphatdyllπosltol glycan, class K 215
409358 AI609021 Hs 292725 ESTs Weakly slmilarto T18818 hypothet 215
442611 BE077155 Hs 177537 hypothetical protein DKFZp761B1514 215
408653 AW410189 Hs 98074 itchy (mouse homolog) E3 ubiqultn prate 215
418849 AW474547 Hs 53565 Homo sapiens PIG M mRNA for maπnosyltraπ 215
418647 AA226198 gb nc26a07 s1 NCI CGAP.Prl Homo sapiens 215
456516 BE172704 Hs 222746 KIAA1610 protein 215
422330 D30783 Hs 115263 eplregulln 215
418437 AA771738 Hs 348000 ESTs, Moderately similar to ALU5 HUMAN A 215
457100 AA417878 Hs 48401 ESTs, Moderately similar to ALU8.HUMAN A 215
445890 AF055019 Hs 21906 Homo sapiens clone 24670 mRNA sequence 215
447957 NM.014821 Hs 20126 KIAA0317 gene product 2 15
442578 AK001643 Hs 8395 hypothetical protein FLJ10781 2 15
400987 C11000939 gI|11464993|ref|NP_065260 1| g 2 15
455642 BE063965 gb QV3 BT0296 140200 085 h01 BT0296Homo 2 15
404029 NM.018936* Homo sapiens protocadhenn be 2 15
452817 AA322859 Hs 284275 Homo sapiens PAK2 mRNA complete eds 215
423165 AI937547 Hs 124915 hypothetical protein MGC2601 215
442327 AA991745 Hs 42522 ESTs 215
457146 BE271371 blphenyl hydrolase like (seπne hydrolas 214
429362 T25833 Hs 200478 ubiquitiπ conjugating enzyme E2M (homolo 214
448748 AI567442 Hs 321666 ESTs Weakly slmilarto ALUF HUMAN llll 214
406596 C15000556*gi|11862941|dbj|BAB19279 1| ( 214
440388 AI693520 Hs 223000 ESTs 214
436314 AI983409 ESTs 214
447433 AA651869 Hs 5320 hypothetical protein 214
433441 R37094 Hs 13742 ESTs 214
458497 AI161428 Hs 75916 splicing factor 3b, subunlt 2, 145kD 214
429938 BE296804 Hs 226377 phosphate cytdylyltransferase 2, ethaπo 214
444859 AW449137 Hs 157487 ESTs 214
421628 AL121317 Hs 106210 hypothetical protein FLJ10813 214
450832 AW970602 Hs 105421 ESTs 214
451622 AW139587 Hs 30579 Homo sapiens cDNA FLJ23070 fis, clone L 2 14
409125 R17268 Hs 343567 axonal transport of synaptc vesicles 214
407347 AA829847 gb od40d07 s1 NCI.CGAP.GCBI Homo sapiens 214
405850 Target Exon 214
437879 BE262082 Hs 5894 hypothetical protein FLJ10305 214
454515 AW803201 Intron of tπchorhlnophalangeal syndro 214
428717 T78001 Hs 133546 hypothetical protein FLJ21120 214
410668 BE379794 Hs 159651 tumor necrosis factor receptor superfam! 214
437673 AW665665 Hs 153034 ESTs 214
440049 R06699 Hs 19769 hypothetical protein MGC4174 214
434766 AA742222 Hs 120634 ESTs 214
458882 R34993 Hs 226666 ESTs Moderately similar to I54374 gene 214
432593 AW301003 Hs 51483 ESTs Weakly slmilarto hypothetical pro 214
458744 AW445183 ESTs 213
419557 N94706 Homo sapiens cDNA FLJ14028 fis, clone HE 213
413771 AA810047 Hs 4112 acetyl Coenzyme A acetyltransferase 2 (a 213
452679 Z42387 Hs 83883 transmembrane, prostate androgen induced 213
444773 BE156256 Hs 11923 hypothetical protein 213
419409 AW297831 Hs 143792 hypothetical protein MGC2656 213
415989 AI267700 ESTs 213
413283 R78669 Hs 23756 hypothetical protein similar to swine ac 213
448648 BE614345 Hs 297214 ESTs, Weakly similar to ALU7.HUMAN ALU S 213
425003 AF119046 Hs 154149 apunnlc/apyπmldinlc endonuclease(APEX 213
447460 AW872495 hypothetical protein FLJ 12439 213
413219 AA878200 Hs 118727 Homo sapiens cDNA FLJ13692 fis, clone PL 213 427550 BE242818 Hs 311609 nuclear RNA hellcase, DECD vaπant of DE 213
446627 AI973016 Hs 15725 hypothetical protein SBBI48 213
421190 U95031 Hs 102482 mucin 5, subtype B, tracheobronchlal 213
419764 BE262524 Hs 93183 vasodilator stmulated phosphoprotein 213
432170 T56887 Hs 18282 KIAA1134 protein 213
436905 N31273 Hs 42380 ESTs 213
419674 AK000170 Hs 92254 synaptotagmiπ-llke 2 213
419125 AA642452 Hs 130881 B cell CLL/lymphoma 11A (zinc finger pro 213
435858 AF254260 Hs 283009 tuftelin 1 213
438614 AB037726 Hs 288348 KIAA1305 protein 213
448889 BE140902 gb IL1 HT0028-240699 001 C11 HT0028 Homo 213
439117 AF085975 gb Homo sapiens full length Insert cDNA 213
404745 Target Exon 2 13
453205 W92881 Hs 117235 ESTs 213
418340 NM 013286 Hs 84162 chromosome 3p21 1 gene sequence 213
413405 AW022253 Hs 215976 ESTs 213
418429 AB010427 Hs 85100 WD repeat domain 1 2 13
441134 W29092 Hs 346950 cellular retinolc acid binding protein 1 213
437277 AA748016 Hs 123370 ESTs 212
409310 R88721 Hs 164584 ESTs 212
435905 AW997484 Hs 5003 KIAA0456 protein 212
401908 C17000154 gi|12003980|gb|AAG43830 1|AF21 2 12
419152 L12711 Hs 89643 transketolase (Wernicke Korsakoff syndro 212
418900 BE207357 Hs 3454 KIAA1821 protein 212
405365 CX001212*gi|7861932|gb|AAF70445 1| (AF2 212
413199 M62843 Hs 75236 ELAV (embryonic lethal abnormal vision 2 12
427300 AA400518 Hs 169395 hypothetical protein FLJ 12015 2 12
421254 AK001724 Hs 102950 coat protein gamma cop 212
424411 NM 005209 Hs 146549 crystallin betaA2 212
421458 NM 003654 Hs 104576 carbohydrate (keratan sulfate Gal 6) sul 2 12
418597 AK001678 Hs 86337 simllarto DNA directed RNA polymerase I 2 12
430539 AK001489 ADP πbosylation factor like 1 212
438730 BE041332 HS 7307 ESTs Weakly simllarto KT12.YEAST KTI12 212
450202 AW969756 Hs 34145 ESTs, Weakly slmilarto B49647 GTP blndl 212
414792 BE314949 Hs 87128 hypothetical protein FLJ23309 2 11
450042 AI681099 Hs 271596 ESTs 2 11
413422 AW176733 Hs 3826 kelch like protein C3IP1 211
448529 T26460 Hs 22550 ESTs 211
408665 T88845 Hs 112200 ESTs, Weakly simllarto ALU7.HUMAN ALU S 211
444381 BE387335 Hs 283713 hypothetical protein BC014245 211
412133 U83460 Hs 73614 solute earner family 31 (copper transpo 2 11
429290 AF203032 Hs 198760 neurofilament heavy polypeptide (200kD) 2 11
418515 AI568453 Hs 19487 ESTs Weakly slmilarto CNIH.HUMAN CORNI 211
419395 BE268326 Hs 90280 5 aminolmldazole 4 carboxamlde πbonucle 211
445892 AV655500 Hs 93961 Homo sapiens mRNA cDNA DKFZp667D095 (fr 211
408559 W30787 Hs 45105 ESTs 211
428826 AL048842 Hs 194019 attractin 211
449188 AW072939 Hs 347187 myotubulaπn related protein 1 211
421307 BE539976 Hs 103305 Homo sapiens mRNA cDNA DKFZp434B0425 (f 211
414057 AI815559 Hs 75730 signal recognition particle receptor (d 2 11
408162 AA993833 Hs 118527 ESTs 211
453028 AB006532 Hs 31442 RecQ protein like 4 210
421777 BE562088 Hs 108196 HSPC037 protein 210
449568 AL157479 Hs 23740 KIAA1598 protein 210
405883 Target Exon 2 10
401095 NM.022363 Homo sapiens LIM homeobox prot 2 10
402840 ENSP00000241321* DJ947L8 1 6 (novel CUB 210
443784 U82670 zinc finger protein 275 210
432393 AW205863 Hs 133988 hypothetical protein FKSG28 2 10
430512 AF182294 Hs 241578 U6 snRNA associated Sm like protein LSm8 2 10
434170 AA626509 Hs 122329 ESTs 210
410001 AB041036 Hs 57771 kallikreiπ 11 210
429438 AC006293 Homo sapiens killer cell Ig like recepto 210
456259 Z44190 Hs 83023 peroxlsomal biogenesis factor 11 B 2 10
410430 AW732554 Hs 59622 Homo sapiens clone IMAGE 3507281, mRNA, 210
421052 AA648486 Hs 118993 ESTs 210
412700 BE222433 ESTs Weakly simllarto I38022 hypothet 210
441549 BE563873 Hs 124005 ESTs, Weakly slmilarto T29899 hypothet 210
418397 NM 001269 Hs 84746 chromosome condensation 1 210
449249 T52285 Hs 193115 Homo sapiens mRNA for KIAA1764 protein, 210
429551 AW450624 Hs 220931 ESTs 210
419677 N77342 Hs 21851 Homo sapiens cDNA FLJ12900 fis clone NT 210
408756 AA524743 ESTs 210
417952 AI192838 dual specificity tyrosine (Y) phosphoryl 2 10
447401 BE618582 Hs 97661 ESTs 210
449721 AW073727 Hs 210265 ESTs 210
406255 Target Exon 210
441676 BE564206 Hs 49889 ESTs 210
418050 R37848 Hs 7177 ESTs 210
454631 AW811324 gb 1L3-ST0141 131099 017-A02ST0141 Homo 210
419575 U43431 Hs 91175 topoisomerase (DNA) III alpha 210
454171 AW854832 gb QV2-CT0261 201099 011 f05 CT0261 Homo 210
433923 AI823453 Hs 146625 ESTs 210
443744 AI084326 Hs 271548 ESTs, Weakly slmilarto I78885 serine/th 210
443713 AI082810 Hs 204934 ESTs 210
418671 D82344 Hs 87202 paired mesoderm homeobox 2b 210 428585 AB007863 Hs 185140 KIAA0403 protein 2 10
404306 Target Exon 2 10
433745 AF075320 Hs 28980 hypothetical protein FLJ 14540 2 10
410232 AW372451 Hs61184 CGI-79 protein 2 10
452335 AW188944 Hs 61272 ESTs 2 10
454427 AW605620 Hs76064 πbosomal protein L27a 2 10
450963 AI864668 Hs48832 ESTs 2 10
427540 R12014 Hs 20976 ESTs 2 10
406740 AA577274 gb nm85g07 s1 NCI_CGAP_Co9 Homo sapiens 2 10
429263 AA019004 Hs 198396 ATP binding cassette, sub family A (ABC1 2 10
419485 AA489023 Hs 99807 ESTs, Weakly similar to unnamed protein 2 10
407644 D16815 nuclear receptor subfamily 1, group D, m 2 10
429058 AF138863 Hs 35254 hypothetical protein FLB6421 2 10
410382 AW664971 Hs 259546 ESTs 2 10
431788 AA992677 thymopoietn 2 10
419200 AW966405 EST 209
436315 BE390513 Hs 27935 hypothetical protein MGC4837 209
421462 AF016495 Hs 104624 aquaponn 9 209
420711 R18398 ESTs 209
419667 AU077005 Hs 92208 a dislntegnn and metalloprotelnase doma 209
412430 AW675064 Hs73875 fumarylacetoacetate hydrolase (fumarylac 209
424197 AF096834 Hs 142989 germ cell specific Y-box binding protein 209
437623 D63880 Hs5719 chromosome condensation-related SMC asso 209
445863 R12234 Hs 13396 Homo sapiens clone 25028 mRNA sequence 209
450306 AL080080 Hs24766 thloredoxln domain containing 209
412939 AW411491 Hs75069 eukaryotic translation elongation factor 209
407276 AI951118 Hs326736 Homo sapiens breast cancer antgen NY BR 209
408283 BE141579 gb QV2-HT0083 071299 018 b05 HT0083 Homo 209
414198 AW605308 Hs75812 phosphoenolpyruvate carboxykmase 2 (mit 209
448556 AW885606 Hs5064 ESTs 209
424505 AA446131 Hs 124918 KIAA1795 protein 209
426691 NM 006201 Hs 171834 PCTAIRE protein kinase 1 209
448545 BE543187 Hs 105097 thymidinβ kinase 1, soluble 209
432901 AI554929 Hs281866 ATPase, H transporting, Iysosomal (vacuo 209
447976 AW972653 Hs293691 ESTs, Highly similar to CR2.HUMAN COMPLE 209
417378 R57256 Hs82037 TATA box binding protein (TBP) associate 209
413643 AA130987 Hs 188727 ESTs 209
408201 AK000568 Hs43654 hypothetical protein FLJ20561 209
443031 AW134696 Hs49418 ESTs 209
450898 N54911 Hs 171765 ESTs 209
455908 BE156306 gb QV0 HT0367-150200 114 h04 HT0367 Homo 209
404053 Target Exon 209
457242 AA457011 Hs80261 gb aa90c11 r1 Stratagene fetal retina 93 209
430354 AA954810 Hs239784 human homolog of Drosophila Scπbble 209
443119 AA312264 Hs7980 hypothetical protein MGC12966 209
400834 NM 002240* Homo sapiens potassium inward 209
408338 AW867079 gb MR1 SN0033 120400002 c10 SN0033 Homo 209
426399 AA652588 Hs301348 Homo sapiens cDNA FLJ13271 fis, clone OV 209
422830 AC007954 Hs 121371 hypothetical protein DKFZp434P0111 208
458676 A1692464 Hs202263 ESTs 208
417939 R53863 Hs337512 ESTs, Weakly similar to ALUB.HUMAN llll 208
452184 R16281 Hs21701 linked to Surfeit genes in Fugu nibπpes 208
408822 AW500715 Hs57079 Homo sapiens cDNA FLJ13267 fis, clone OV 208
429305 AF095727 Hs 287832 myelln protein zero like 1 208
419355 AA428520 Hs 90061 progesterone binding protein 208
447887 AA114050 Hs 19949 caspase 8 apoptosis-related cystelne pr 208
421443 BE550141 Hs 156148 hypothetical protein FLJ13231 208
451422 AB002336 Hs 26395 erythrocyte membrane protein band 4 1-lι 208
423797 BE259364 Hs 132898 fatty acid desaturase 1 208
401192 Target Exon 208
440028 AW473675 ESTs, Weakly simllarto T17227 hypothet 208
449769 AI668700 Hs 226564 ESTs, Moderately similar to ALU6.HUMAN A 208
450330 AW500775 Hs 24817 hypothetical protein FLJ20136 208
453518 AW503205 Hs 27268 gb UI-HF BN0 akt-g 03 0 Ul r1 NIH.MGC.50 208
420750 AW190215 Hs 62348 hypothetical protein FLJ11753 208
434033 AI631749 Hs 156616 ESTs, Weakly simllarto alternatively sp 208
425001 U55184 Hs 154145 hypothetical protein FLJ 11585 208
414809 AI434699 Hs77356 transferrin receptor (p90, CD71) 208
411580 AL080088 Hs70877 DKFZP564K2062 protein 208
432458 A1968598 Hs78768 malignant cell expression enhanced gene/ 208
459646 AW883968 Hs321190 gb QV3 OT0063 290300-135 c04 OT0063 Homo 208
434350 AL042940 Hs93872 KIAA1682 protein 208
436610 AW611912 Hs98751 ESTs 208
413045 X92121 Hs75180 protein phosphatase 5, catalytic subunit 208
416855 AA188763 Hs36793 hypothetical protein FLJ23188 208
423137 NM 007212 Hs 124186 ring finger protein 2 208
427239 BE270447 ubiqultin carrier protein 208
426526 BE617944 Hs 170226 Homo sapiens clone 23579 mRNA sequence 207
411619 AI418609 Hs71040 hypothetical protein FLJ20425 207
420762 U51699 dollchyl phosphate (UDP-N-acetylglucosam 207
457133 M54968 v-KI-ras2 Kirsten rat sarcoma 2 viral on 207
414581 AA256213 Hs72010 ESTs 207
430750 AI650360 Hs 100256 ESTs 207
405760 Target Exon 207
436862 AI821940 Hs 116567 ESTs, Moderately similar to ALU8.HUMAN A 207
453690 AI674872 Hs 107000 hypothetical protein FLJ11294 207 435750 AB029012 Hs 4990 KIAA1089 protein 207
428977 AK001404 Hs 194698 cyclin B2 207
431188 W05656 Hs 169755 ESTs 207
410407 X66839 Hs 63287 carbonic anhydrase IX 207
418874 T60872 gb yb72h11 s1 Stratagene ovary (937217) 207
416305 AU076628 Hs 79187 coxsackle virus and adenovirus receptor 207
441252 AW360901 hypothetical protein MGC4399 207
420596 NM 002692 Hs 99185 polymerase (DNA directed), epsilon 2 207
408546 W49512 Hs 46348 bradykimπ receptor B1 207
404071 C12000514* gi|7302471|gb|AAF575561| (AE 207
408946 AW854991 Hs 255565 ESTs 207
420614 AL110291 Hs 99364 putative transmembrane protein 207
404754 C3001259 gi|476355|plr||A46762 myosln al 207
424055 AA337234 gb EST42299 Endometrial tumor Homo saple 206
434875 AW974785 Hs 290831 ESTs 206
418793 AW382987 Hs 88474 prostaglandiπ-eπdoperoxlde synthase 1 (p 206
405710 CX000682 gl|12741327|ref|XP_0088332| zl 206
421604 AW293880 Hs 248367 MEGF11 protein 206
447370 AW248150 Hs 18349 mltochondrial nbosomal protein L15 206
411800 N39342 Hs 103042 mlcrotubule associated protein 1B 206
442993 BE018682 Hs 166196 ATPase, Class I, type 8B, member 1 206
434075 AW003416 Hs 160604 ESTs 206
428583 AA430589 Hs 75410 heat shock 70kD protein 5 (glucose regul 206
422975 AA347720 Hs 122669 KIAA0264 protein 206
451273 NM 014811 Hs 26163 KIAA0649 gene product 206
433399 N46406 Hs 84700 slmilarto phosphatidylcholine transfer 206
431849 AI670823 Hs 85573 hypothetical protein MGC10911 206
420324 AF163474 Hs 96744 prostate androgen regulated transcnpt 1 206
443677 AV646096 Hs 282990 ESTs Weakly similar to B34087 hypotheti 206
405779 NM.005367 Homo sapiens melanoma antigen, 206
439357 AW955708 Hs 100651 golgi SNAP receptor complex member 2 206
400880 NM.000611* Homo sapiens CD59 antgen p18 205
415079 R43179 Hs 22895 hypothetical protein FLJ23548 205
415788 AW628686 Hs 78851 KIAA0217 protein 205
405697 gb Human homeobox-like mRNA 205
431441 U81961 Hs 2794 sodium channel, nonvoltage-gated 1 alpha 205
408086 AW351543 Hs 42514 hypothetical protein F25965 205
458335 AI762479 gb wh91a04 x1 NCI.CGAP.CLL1 Homo sapiens 205
401898 NM.024722* Homo sapiens hypothetcal pro 205
425255 AW374106 Hs 155356 hypothetical protein MGC2840 simllarto 205
413976 BE295452 Hs 75655 procollageπ-proline, 2-oxoglutarate 4 di 205
421937 AI878857 Hs 109706 hematologlcal and neurological expressed 205
426329 AL389951 Hs 271623 nucleopoπn 50kD 205
445243 AI217439 ESTs, Weakly slmilarto ALU1.HUMAN ALU S 205
451930 BE259124 Hs 27262 Homo sapiens clone 25110 mRNA sequence 205
431846 BE019924 Hs 271580 uroplakin lB 205
410847 AW807090 gb MR4 ST0062 031199 018 d12 ST0062 Homo 205
449523 NM 000579 Hs 54443 chemokine (C C motf) receptor 5 205
411051 AW853931 gb RC3 CT0254 180200026-e04 CT0254 Homo 205
418967 NM.001725 Hs 89535 bactericidal/permeability increasing pro 205
408841 AW438865 Hs 256862 ESTs 205
403509 KIAA0539 gene product 205
418898 T66847 Hs 194040 ESTs, Weakly similar to I38022 hypothet 205
453438 AI469935 Hs 22792 ESTs 205
443084 AI827639 Hs 125539 ESTs 205
410656 BE161335 Hs 321717 ESTs, Weakly simllarto S22765 heterogen 205
441879 AI521936 Hs 107149 novel protein similar to archaeal, yeast 205
453081 AI951203 Hs 223345 ESTs 205
455211 AW866449 gb QV4 SN0024 170400 176 a12 SN0024 Homo 205
448824 L41147 Hs 22180 5 hydroxytryptamiπe (serotonin) receptor 205
418319 AW611703 Hs 190173 ESTs, Weakly similar to A46010 X linked 205
442317 AI915599 Hs 129225 ESTs 205
400249 Eos Control 205
439092 AA830149 gb oc44f08 s1 NCI.CGAP.GCBI Homo sapiens 205
448390 AL035414 Hs 21068 hypothetical protein 205
422661 NM 014700 Hs 119004 KIAA0665 gene product 205
444682 R37390 Hs 21119 ESTs 205
428315 AA688152 Hs 98505 ESTs 205
440953 A1683036 Hs 124135 Homo sapiens cDNA FLJ13051 fis, clone NT 205
427178 AA398866 Hs 97542 Homo sapiens tests-development related 205
414212 AA136569 Hs 10848 KIAA0187 gene product 205
415892 H08267 Hs 302330 ESTs, Moderately similar to JC5238 galac 205
424624 AB032947 Hs 151301 Ca2-tdependent activator protein for seer 205
454838 AW833984 gb QV0 TT0010031199 045-a05 TT0010 Homo 205
414709 AA704703 Hs 77031 Sp2 transcnpton factor 205
401463 hlstone deacetylase 5 205
453849 N35321 Hs 278611 UDP-N-acetyl alpha-D-galactosamlπe polyp 205
453344 BE349075 Hs 44571 ESTs 205
431790 AA650250 Hs 272076 ESTs 205
457898 AI382260 Hs 129943 ESTs, Weakly slmilarto high πsk human 205
443423 AW162357 Hs 7023 ESTs 205
426172 AA371307 Hs 125056 ESTs 205
423871 AA331906 Hs 175596 gb EST35805 Embryo, 8 week 1 Homo sapien 205
432146 AW081072 Hs 115960 KIAA0939 protein 205
422906 U80773 Hs 121580 Human EST clone 42944 mariner transposon 205
444822 BE164351 Hs 292767 hypothetical protein FLJ23109 205 422273 AA307796 Hs 269548 ESTs 205
418690 AK000052 Hs 87293 hypothetical protein FLJ20045 205
400730 Target Exon 205
429128 AA446869 Hs 119316 ESTs 205
416732 H81066 Hs 285017 hypothetical protein FLJ21799 205
423248 AA380177 Hs 125845 ribulose 5-phosphate 3-epimerase 205
420544 AA677577 Hs 98732 Homo sapiens Chromosome 16 BAC clone CIT 205
427356 AW023482 Hs 97849 ESTs 205
435147 AL133731 Hs 4774 Homo sapiens mRNA, cDNA DKFZp761C1712 (f 205
440184 AB002297 Hs 7022 dedicator of cyto-klnesis 3 205
415025 AW207091 Hs 72307 ESTs 205
409205 AI952884 Hs 14832 ESTs, Moderately similar to unnamed prot 205
437672 AW748265 Hs5741 flavohemoprotein b5? 205
413916 N49813 Hs 75615 apollpoproteln C II 205
403794 Target Exon 205
437287 AA748180 Hs 159346 hypothetical protein FLJ21369 205
435542 AA687376 ESTs 205
444391 AL137597 HS 11114 hypothetical protein dJ1181N31 205
408353 BE439838 Hs 44298 mitochondπal πbosomal protein S17 205
428865 BE544095 Hs 164960 BarH like homeobox 1 205
421282 AA286914 Hs 40782 ESTs 205
431250 BE264649 Hs 251377 taxol resistance associated gene 3 205
452206 AW340281 Hs 33074 Homo sapiens, clone IMAGE 3606519, mRNA, 205
435730 AB020635 Hs 4984 KIAA0828 protein 204
404496 Target Exon 204
449378 AW664026 Hs 59892 ESTs 204
447528 AI612027 Hs 76277 Homo sapiens, clone MGC 9381, mRNA, comp 204
412276 BE262621 Hs 73798 macrophage migration Inhibitory factor ( 204
400547 C10000695 gι|3153229|gb]AAC17225 1| (AF0 204
454279 AW295650 Hs 255453 ESTs, Weaklysimliarto ALUI.HUMAN ALU S 204
435784 AA705437 ESTs 204
452731 AW451468 Hs 257455 ESTs 204
456381 AA236606 gb zr99b10 r1 NCI CGAP.GCB1 Homo sapiens 204
436028 AA731124 Hs 15430 ESTs 204
417169 R13550 Hs 21388 ESTs 204
450052 AI681298 Hs 236524 ESTs 204
412520 AA442324 Hs 795 H2A hlstone family, member O 204
456756 AI494486 Hs 148767 ESTs 204
416680 AW245540 Hs 79516 brain abundant, membrane attached signal 204
417630 D63877 Hs 82324 KIAA0157 protein 204
409617 BE003760 Hs 55209 Homo sapiens mRNA, cDNA DKFZp434K0514 (f 204
440603 AL121733 Hs 7299 Novel human gene mapping to chomosome 1 204
412636 NM 004415 desmoplakm (DPI, DPII) 2 04
454516 AW803341 gb IL2-UM0079090300 050 D03 UM0079 Homo 204
414054 BE244328 Hs 288539 hypothetical protein FLJ22191 204
419058 AW675039 Hs 1227 amlnolevulinate, delta-, dehydratase 204
422565 BE259035 Hs 118400 singed (Drosophila) like (sea urchin fas 204
447782 AI668903 ESTs 204
413645 AA130992 gb zo15e02 s1 Stratagene colon (937204) 2 04
456534 X91195 Hs 100623 phospholipase C, beta 3, neighbor pseudo 204
433747 AI004012 Hs 143752 ESTs 204
433071 BE150229 Hs 281564 retnal outer segment membrane protein 1 204
410840 AW806924 gb QV4-ST0023 160400-172 h10 ST0023 Homo 204
425304 AA463844 Hs 31339 fibroblast g rowth factor 11 204
447711 AI459554 Hs 161286 ESTs 204
449226 AB002365 Hs 23311 KIAA0367 protein 204
411957 AW246216 Hs 32058 Homo sapiens C1orf19 mRNA, partial eds 204
423226 AA323414 Hs 146109 ESTs, Weakly slmilarto T28937 hypothet 204
436045 AB037723 Hs 5028 DKFZP564O0423 protein 204
417433 BE270266 Hs 82128 5T4 oncofetal trophoblast glycoprotein 204
424744 AW175781 Hs 152720 M-phase phosphoprotein 6 203
437478 AL390172 Hs 317432 branched chain amlnotransferase 1, cytos 203
445003 AI204593 Hs 148698 ESTs 203
432674 AA641092 Hs 257339 ESTs, Weakly similar to I38022 hypothet 203
431763 NM 005136 Hs 268538 potassium voltage-gated channel, Isk rel 203
435647 AI653240 Hs 49823 ESTs 203
419341 N71463 Hs 118888 ESTs, Weakly simllarto ALU1 HUMAN ALU S 203
414486 AW305026 Hs 193974 ESTs, Weakly simllarto ALU1.HUMAN ALU S 203
430383 AI861854 Hs 210778 hypothetical protein FLJ10989 203
423994 X01057 Hs 1724 Interleukin 2 receptor, alpha 203
430828 AI763257 Hs 86327 Homo sapiens cDNA FLJ22431 fis, clone H 203
438307 AB011093 Hs 6150 hypothetical protein MGC15913 203
419904 AA974411 Hs 18672 ESTs 203
412017 AA812143 Hs 23767 hypothetical protein FLJ12666 203
429671 BE379335 Hs 211594 proteasome (prosome, macropaln) 26S subu 203
437258 AL041243 Hs 174104 ESTs 203
407103 AA424881 Hs 256301 hypothetical protein MGC13170 203
439930 AI218704 Hs 144975 ESTs 203
458207 T28472 Hs 7655 U2 small nuclear nbonucleoproteln auxll 203
452882 AW972990 Hs 196270 folate transporter/carrier 203
406542 C19000728* gil12585552|sp]Q9Y2Q1|Z257_HU 203
439941 AI392640 Hs 18272 amino acid transporter system A1 203
452277 AL049013 Hs 28783 KIAA1223 protein 203
441959 BE536998 Hs 200360 Homo sapiens cDNA FLJ13027 fis, clone NT 203
424899 AL119387 Hs 119062 ESTs 203
418683 U90908 Hs 87241 hypothetcal protein from clones 23549 a 203 437818 AA769054 gb oa74a08 s1 NCI.CGAP.GCBI Homo sapiens 203
433068 NM.006456 Hs 288215 slalyltransferase 203
418057 NM 012151 Hs 83363 coagulation factor Vlll-associated (intr 203
439564 W77911 Hs 110006 ESTs 203
424287 AL133105 Hs 144633 hypothetical protein DKFZp434F2322 203
424075 AI807320 Hs 227630 RE1-sιlencιng transcnpton factor 203
426746 J03626 Hs 2057 uridlne monophosphate synthetase (orotat 203
421690 AW162667 Hs 106857 calblndin 2, (29kD, calretinln) 202
426096 D87436 Hs 166318 llpln 2 202
421626 AI739285 Hs 153959 hypothetical protein MGC15436 202
439768 AI337300 Hs 173138 hypothetical protein MGC4604 202
459001 AI761313 Hs 204605 ESTs 202
451044 AL117665 Hs 25882 DKFZP586M1824 protein 202
448262 AW880830 Hs 186273 Homo sapiens qulescin Q6 (QSCN6) 202
425256 BE297611 Hs 155392 collapsin response mediator protein 1 202
409632 W74001 Hs 55279 seπne (or cystelne) proteinase Inhlblto 202
414045 NM 002951 Hs 75722 πbophonn II 202
410072 BE384447 Hs 16034 hypothetical protein MGC13186 202
408212 AA297567 Hs 43728 hypothetical protein 202
452732 BE300078 Hs 80449 Homo sapiens, clone IMAGE 3535294, mRNA, 202
436251 BE515065 Hs 296585 πucleolar protein (KKE/D repeat) 202
422532 AL008726 Hs 118126 protective protein for beta galactosidas 202
441297 AW403084 Hs 7766 ubiquitn conjugating enzyme E2E 1 (homo 202
450649 NM 001429 Hs 25272 E1A binding protein p300 202
432673 AB028859 Hs 278605 DnaJ (Hsp40) homolog, subfamily B, membe 202
424996 AF006005 Hs 154104 plelomoφhlc adenoma gene like 2 201
418514 AW068487 Hs 25413 TOLLIP protein 201
406687 M31126 matnx metalloprotelnase 11 (stromelysln 201
400133 Eos Control 201
449701 AW952323 Hs 129908 KIAA0591 protein 201
401405 Target Exon 201
434042 AI589941 Hs 8254 Homo sapiens, Similar to tumor different 201
408618 AK000637 Hs 46624 HSPC043 protein 201
447757 AA071276 Hs 19469 KIAA0859 protein 201
432221 M21191 Hs 273415 aldolase A, fructose blsphosphate 201
400219 Eos Control 201
400845 NM.003105* Homo sapiens sortilin-related 201
412247 AF022375 Hs 73793 vascular endothelial growth factor 201
413248 T64858 Hs 26966 hypothetical protein DKFZp547J036 201
419663 AA394208 Hs 92198 calcium-regulated heat-stable protein (2 200
444418 AL034417 Hs 11169 Gene 33/Mig 6 200
414653 M24486 Hs 76768 procollagen-proliπe, 2-oxoglutarate 4 di 200
425157 NM 006227 Hs 283007 phospholipid transfer protein 200
446160 AW392197 Hs 218003 ESTs 200
444042 NM 004915 Hs 10237 ATP-blndiπg cassette, sub-family G (WHIT 200
456895 AA354771 Hs 43047 Homo sapiens cDNA FLJ13585 fis, clone PL 200
458421 AI279978 Hs 22547 ESTs 200
412999 BE046255 gb Iw38g10 x2 NCI.CGAP.RDF2 Homo sapiens 200
458984 AA011185 Hs 221189 hypothetical protein FLJ14431 200
444601 AV650521 Hs 282449 ESTs, Moderately similar to ZN91.HUMAN Z 200
403935 Target Exon 200
421258 AA286731 gb zs53d08 r1 NCI.CGAP.GCBI Homo sapiens 200
409628 AB021865 Hs 55276 potassium voltage-gated channel, Shal re 200
404705 Target Exon 200
404592 NM.022739* Homo sapiens E3 ubiquitn llg 200
456425 AA423846 Hs 15220 zinc finger protein 106 200
429731 AK001592 Hs 212172 beta carotene 15,15-dιoxygenase 200
454363 AW816274 Hs 250154 hypothetical protein FLJ12973 200
414390 BE281040 gb 601156234F1 NIH.MGC.21 Homo sapiens c 200
458215 AA928160 gb on86f10 s1 Soares NFL T GBC S1 Homos 200
447500 AI381900 Hs 159212 ESTs 200
445790 AV655170 Hs 49015 chromosome 21 open reading frame 35 200
445511 AA846512 Homo sapiens cDNA FLJ14459 fis, clone HE 200
402239 Target Exon 200
448798 Z28671 Hs 58606 SNRPN upstream reading frame 200
437829 AI358522 Hs 103834 ESTs 200
452470 AI903246 gb RC-BT029 070199-024 BT029 Homo sapien 200
439932 AI589851 ESTs 200
425146 AW954627 Hs 48794 gb EST366697 MAGE resequences, MAGC Homo 200
417609 AI189754 Hs 86320 ESTs 200
430838 N46664 Hs 169395 hypothetical protein FLJ12015 200
454525 BE280421 Hs 94499 ESTs 200
454607 AW809845 Hs 288568 hypothetical protein FLJ22644 200
449016 BE615864 gb 601279735F1 NIH MGC 39 Homo sapiens c 200
402889 ENSP00000217123* FLJ00118 protein (Fragm 200
427696 R39126 Hs 8038 ESTs 200
423077 Z78283 gb Z78283 Homo sapiens brain fetus Homo 200
441373 AI266421 Hs 120179 Homo sapiens cDNA FLJ22133 fis, clone H 200
434328 BE564937 Hs 15984 pp21 homolog 200
443826 AI214805 Hs 27232 ESTs 200
443273 A1042063 Hs 132156 ESTs 200
452999 AI755080 Hs 26481 SBBI26 protein 200
451684 AF216751 Hs 26813 CDA14 200
430707 AF082350 Hs 247820 bone morphogenetc protein 15 200
408006 H57654 Hs 303345 ESTs, Weakly simllarto I38022 hypothet 200
400750 Target Exon 200 419321 N48146 Hs 269069 ESTs, Weakly slmilarto I38022 hypothet 200
459234 AI940425 gb CMO CT0052-150799 024 c04 CT0052 Homo 200
436277 R88520 Hs 120917 ESTs 200
451106 BE382701 Hs 25960 N MYC oncogene 200
418284 AW948651 Hs 26002 LIM domain binding 1 200
413402 T24065 gb seq2245 HMSWMYK Homo sapiens cDNA do 200
438701 AA937112 Hs 207788 ESTs 200
434481 AF143330 Hs 12621 Homo sapiens clone IMAGE 112577 mRNA seq 200
415121 D60971 Hs 34955 Homo sapiens cDNA FLJ 13485 fis, clone PL 200
432492 AW275110 ESTs 200
440772 AA905574 Hs 197444 ESTs 200
458342 AI003931 Hs 334583 πng finger protein 23 200
453666 AW015681 Hs 135229 ESTs, Weakly slmilarto A2BP.HUMAN ATAXI 200
409988 N27687 Hs 334334 transcnpton factor AP-2 alpha (actvat 200
444430 AI611153 Hs 6093 Homo sapiens cDNA FLJ22783 fis, clone K 200
458422 AI344782 DnaJ (Hsp40) homolog, subfamily C, membe 200
434636 AA083764 hypothetical protein MGC3178 200
408504 AW205908 Hs 73614 ESTs, Weakly similar to 2109260A B cell 200
418403 D86978 Hs 84790 KIAA0225 protein 200
418496 AI564857 Hs 27888 ESTs, Weakly similar to εenπe/threonine 200
416742 R38644 Hs 248420 ESTs, Moderately similar to A47582 B eel 200
442333 AI650877 Hs 129302 ESTs 200
425147 AW291265 Hs 334636 hypothetical protein MGC2615 200
415642 U19878 Hs 336224 transmembrane protein with EGF like and 200
414684 AW630023 Hs 76893 3 hydroxybutyrate dehydrogenase (heart, 200
453354 W55946 Hs 234863 Homo sapiens cDNA FLJ12082 fis, clone HE 200
442007 AA301116 Hs 142838 nucleolar phosphoprotein Nopp34 200
434326 NM 005619 Hs 3803 retculon 2 200
456487 AF064804 suppressor of Ty (S cerevisiae) 3 homolo 200
443767 BE562136 Hs 9736 proteasome (prosome, macropain) 26S subu 200
414569 AF109298 Hs 118258 prostate cancer associated protein 1 200
419829 AI924228 Hs 115185 ESTs, Moderately similar to PC4259 ferri 200
448360 AL117560 Hs 306352 Homo sapiens mRNA, cDNA DKFZp566P2324 (f 200
410025 BE220489 Hs 113592 ESTs, Moderately similar to I54374 gene 200
436961 AW375974 Hs 156704 ESTs 200
443823 BE089782 Hs 9877 hypothetical protein 200
436887 AW953157 Hs 193235 hypothetical protein DKFZp547D155 200
421808 AK000157 Hs 108502 hypothetical protein FLJ20150 200
418375 NM 003081 Hs 84389 synaptosomal associated protein, 25kD 200
446565 D13757 Hs 311 phosphonbosyl pyrophosphate amidotransf 200
450737 AW007152 Hs 63325 transmembrane protease, seπne 4 200
433184 AA147979 Hs 285005 mltochondrial import receptor Tom22 200
427621 BE621182 Hs 179882 hypothetical protein FLJ 12443 200
TARI F 12B
Pkey Unique Eos probeset identifier number
CAT number Gene cluster number
Accession Genbank accession numbers
Pkey CAT number Accession
428342 6712.1 AK056315 AI015524 AA724079 BI713619 AI377728 AW293682 AI928140 AI092404 AI085630 AA731340 BM469629 AW968804 AA425658
AA769094 BF446026 AW118719 AI332765 AW500888 AW576556 AI859571 AW499664 AW614573 AW629495 AW505314 W74704
AI356361 AI923640 AW070509 AI521500 AL042095 AA609309 AA761319 AI381489 H45700 AA761333 AW265424 AA909524 AA635311
AA649040 AI392620 Z40708 AI985564 AW263513 AA913892 AI693486 AW263502 AI806164 AW291137 BI061872 BI059498 AA134476
AW084888 AA036967 AW370823 T55263 BI002756 AA489664 BF827261 W74741 BF963166
412446 63467.1 BC021735 AI669212 AL120184 AI769949 BE701002 BE184363 BE819031 BG702238 BF090049 BF963318 BF961912 BF943013
AA934514 AA151245 BF960659 AA987907 Z41449 BF908059 BF908053 BF908049 BE699424 BF908060 BF962832 BF952020 BF963134
BI035538 BF908052 BF908057 BF090026 BF943158 AI632924 BF512340 BF952021 BF960776 BF943437 BF942847 AI768015 F09778
F04816 F02721 AA102645 AI633838 AA617929 BF947001 BI035448 BE935876 AW890837 AW898604 BF957405 BF963433 BG704815
447329 9170.1 BC001573 AK074197 AW967044 AW360965 AW612048 AI765501 AA112034 BI859391 BI334670 W63553 AV706135 AW024203 BI194441
AV655141 AA316041 BE280583 BG428780 BE267060 AV648926 AA317168 BI222294 BG437688 BE709273 AI951240 A1611162
AW970792 H89338 BE543309 AL036038 R26941 BI765176 AA209487 AA111975 AA086463 AW192209 AW025245 BF511894 AW264490
AW014985 AA947336 F15843 BI335083 AA563626 BE546579 AW470009 AA083693 BE090517 BF970294 BG427898 BE541527
451807 17758.2 BM479185 AL552795 AL577722 BF038888 BM127617 BF510346 AW450652 AA865478 AW449519 BM127314 AI806539 AW449522
AA993634 AI827626AA904788
449349 852.3 BG679689 AW856638 BM016319 BE327123 AW772128 BE693337 BE938262 BG013928 BF892774 BF894765 BF892588 BF890995
BE155056 BE153569 AI934407 BE672538 A 204203 AA778306 BE502974 AI718504 AA778312 AW008224 AW299732 AI911561
AI867457 AI521962 AI640173 A1823832 AI288888 BE467960 AI934441 AA483527 AW612103 AI802712 AW342106 A1580299 AW083293
AI700874 AW469932 AI583726 AW302136 BE327360 AW614404 C02300 AA934834 F29737 AI262050 AA934619 AA535965 BF196507
AA393480 BF086615 AI825386 AA009773 BI333272 T93614 AW770207 BF766665 T64641 W92713 R94110 T89897 BF086603 T93659
AA001207 BE539257 BE541430 BE160783 BE155304 BE155454 BF891405 BF762818
429228 215430.1 BG676155 BM009591 AI479075 A1025794 AI017967 AA448270 BE466812 AA853422 AI392649 BG952034 AA513384 BF840124 BE714620
AW969605 AI553633
411605 10026.3 BG256892 H10532 N46614 R52610 AW977696 BM460488 W56819 BI042183 BG977498 BE767451 BF870009 BG477472 R61137 R14274
R20259 R09686 BI838226 BF034269 AA429173 BE741829 AW867495 AI123683 AW006831 BE831162 AW452753 AV742717 W86152
BF115102 AI633815 BF921562 AA094230 BE092587 W86151 AA526153 A1672156 BF914496 R12579 BF852352 AA699780 T57386
BF903022 R09933 AA678298
451752 10408.5 AB032997 AI141678 AW978722 BE467119 AI761408 BF727385 AW237035 AI934521 BF436248 AI479668 Z40632 AA832081 AW295901
BF057835 BE465977 AI621269 BE465983 BF756369 N74056 AI817896 AA716567 AA934774 H62600 H09497 BF943762 BE395335
BE883333 444172 49300.2 BF526827 AA513594 AL515291 AV648373 AV648176 AA916789 BF002906 AW469960 BE466943 AI367749 AI559715 BF431260
AA937968 AI422252 AI288937 BF962778 AA909144 BF960004 BE671534 AI271719 BF925335 BE669504 BF433431 BF924838 AI218062
AW960577AV722716 BI859067 BF944964 BE147740 BF938993 400205 2538.1 NM 006265 D38551 X98294 BM477931 B 461566 AU123557 AU133303 AU134649 AW500421 BM172439 AW500587 AW503665
AW504355 AW503640 BM152454 AW505260 AI815984 AW504075 AW500716 AL597310 BC001229 BM474371 AA984202 AU135205
BE090841 AW163750 BF747730 BF898637 AI206506 AV660870 AV692110 AW386830 AV656831 N84710 AW993470 BF086802
BF758454 BG960772 BF757769 BI870853 BE018627 C75436 AW148744 BF757753 BG622067 BE909924 AA708208 BG530266 BF968015
AW992930 BF888862 BG536628 AA143164 AW748953 BG498922 BF885190 BF889005 BF754781 BF800003 BM476529 AI627668
AW028126 AL046011 BF590668 AI017447 AA579936 AI367597 AA699622 BE280597 AI124620 AI082548 AW274985 AA677870 AI056767
BE551689 AA287642 H94499 AI752427 AI652365 AW002374 AW062651 AA360834 N68822 AU135442 AU125960 Z78334 BE545813
AI092115 BF312771 BF242859 BG533616 BG533761 BG164745 BG492433 BM473183 AA172043 AA172069 AU157092 AU151353
AU155318 BE302211 AI375022 AA085641 AU157923 H88858 AA132730AA115113 AA909781 A1475256 AA424206 AW572383 AW084296
AI184820 AI469178 AA782432 H92184 AA340562 BF195818 AA852821 AW576342 AA827107 AA173317 AW190014 AI918514 AA729372
AA729718 AI055958 AA331424 BE328601 AA515690 BI018896 AW628277 AA748368 AA626222 BG492636 AW38062O BF800058
AW370956 AA290909 R25857 BG952995 BF801437 AA172077 AU155890 AU149783 AI720904 AA902936 AA865727 AI470830 AV740677
AA142982 AA482485 AU145485 AW576399 AU156042 R63448 BF246427 BE928472 D25910 BF758439 BF968785 BE565238 AA355981
AI905607 BG291148 BG533096 BG532888 BF030886 BG613756 BE928471 BG574501 AA187596 AA361196 T95557 BG531446
BG527242 BG527513 BG611106 AA085995 BF847252 BG024608 BE540261 BG531236 AL579993 BG108733 BG483503 BG571032
BG492505
419631 2743.1 BC022323 AF204171 NM.022361 BM264431 BE670789 AW188117 AI025298 AA861832 H84897 AI382294 AA662874 AW993380
BE813742H84368 AI188074 N20482 H84369 400277 170.1 Y00281 NM.002950 BC010839 BC007995 BG675232 BM468552 AL555484 BG831516 BF035300 BG677277 BF852972 BE314901
BF850656 AI371816 AA292474 AA375747 AA308414 BM454544 BI333370 BM049921 BI461428 BI465007 BI223401 BE856245 AW821164
BF914775 BF914761 AU125835 BI222678 BI091137 BF340536 BM462798 BI224452 BG707915 AL569160 AA443815 AW572867
AW363410 BF739268 BG010283 B1013120 BF818845 BF763468 AA305165 AI630370 AA039826 R24906 H02046 T96891 BF981330
AW936510AA478169 H04587 BG166574 B1869342 BE562482 BE539637 AA165089 AL579118 AL553699 BE044054 AW117440 AI520674
BF435417 AW245648 AI952404 T29534 AU153459 AU152168 AW591591 AU146918 A1393187 AA478013 AU148143 AI224471 AI640728
AI871537 AW264752 N93787 AI189357 AV756134 AI471659 AU147466 AA779206 AU149419 AU149104 AU159135 AA312221 AW445119
AW021912 AI799771 F04407 AI285530 AI914643 AW068751 AA513325 AA164627 AA639285 AA569644 T96892 AI923594 BF439180
BI770936 BF032438 AU154884 AA682793 AW072992 AU158815 AI884444 AL048031 AU158922 AU152546 AI695187 AL048033 AI245650
AU148507 AW467451 BE536868 BF913001 BF062707 AL573082 AW067993 AA523354 BE886727 AI890705 AU159092 AI982693
AI817553 AA236729 AI687858 BG163767 A1524675 AI678155 AA127100 AI762661 AU159718 AI469720 AA483627 AW131696 R26868
AI199885 AW875614 AW938694 AW578974 BI763988 BG819168 BE874767 BG978292 BE162948 AL555483 AW189719 T56783 AI018819
AI476552 BI492837 AI824440 BG996262 AA932887 AI380726 R79530 AA622108 AI262575 T56782 R27437 BE784153 AW129549
AI675567 A1866759 BG987935
449444 2735.1 U59185 NM.004696 AV734324 A1245349 AA369517 H88760 D79128 AA970406 H01059 H88761 H03446 BG620383 AU135008 AU136895
AU158158AU155762 R73608 R65751 R23756 N74630 AW078687 BE439761 BE786351 R68994 BE785867AW297502 AW297553
BG431545 AW814843 BF382644 BG429539 BE929862 BF811258
442961 60316.2 BE966247 BE220885 BE467384 BE350135 BE672094 AI811582 AW665254 AA772731 AI283601 AA417067 AW197746 AI868357
AI792143 AA931120 AI758506 AA843761 BE737582 AW379586 N38812 BG567321 H13257
443695 2041612 BE535598 AW204099 AW301249 AA609749 BF917914 AA775742 AV646137 AV646389 AA314747 422150 782.1 BI086421 BF059136 AW003898 BF446659 AI632891 AI628067 AI703179 AI961149 BF111022 AW614154 BE674215 AA687350 AA779426
BF591963 AW243344 AI356530 AI492508 AI694049 AI090422 AA465307 AI273387 BE674625 AW271971 AA969153 AW468593 AA984014
A1817491 AA970258 AI914450 AI018697 AW577591 AW577616 AA382101 AW954455 AI867266 AI707995 AI337384 BF208406 BF037100
BF223433 BF195517 BE673984 BF224124 BE813387 BG036579 BI553906 AA304995 AW361269 AW754160 AW361276 AW361271
AI867118 AW805555 AW361284 AW954458 AW958551 BG681507 H79011 AW205696 AW134957 AA747667 AW753296 BF939060
AW958549 BF910827 BG573750 BG168639
437834 294580.1 BG110129 AW749287 BE535498 AW749299 AW749293 AW749302 AW749298 AW749291 AW749294 AW749289 AW749288 AW749296
AA769294 AW749297 AW749295 AW749292 BE002573
439574 689966.1 BG532820 AW246001 AI469788 AI350090 AI446788 BE549330 W84862 AA837988
433023 3970.8 BE999967 BF438599 AW864793 AI802899 BE815132 AW468888 AI672189 AI052004 BF112024 AA772335 AW275054 AA573845
AI144148 AI968683 AA846676 AA927355 H80424 AW973295 R88209 F29868 BE928871
407198
447349 1063443.1 BE743847 AW809603 BM469626 AI375546
458098 23945 1 AI082245 BE467534 A1797130 BE467063 BE467767 BE218421 AI694996 BE327781 BE327407 BE833829 AA989054 AA459718 BE833855
BE550224 AA832519 AF086393 AV733386 BE465409 N29245 W07677 AA482971 BE503548 H18151 AA461301 W79223 W74510
AI090689 AL600773 AL60O781 N46003 R28075 R34182 BE071550 AW885857 AI276145 A1276696 H97808 N20540 AI468553
430935 15297.3 BC017923 AA789302 AW466994 BF513878 AI819642 AI184913 AW469044 AI220572 AW072916 AI280239 AI473611 AW841126 D60937
AA489195 N59350 AA693435 BG531204 AA484243 AW514092 412537 14066.1 AK025201 AA425472 AI694282 BG057305 AA907787 AI286170 AI684577 AJ420494 AI809865 BF058095 AI478773 AI160445 AL044114
AW665529 A1129239 AW297152 AI268215 AI469807 AI969353 BE552356 N66509 AA736741 AA382555 AW075811 AV759188 BI259364
BF445142 BG232065 Al 141758 A1631202 AH 67566 AI208445 AA889823 BF982682 N90322 BI090882 BF208005 AW953918 AL044113
AI016793 AA382556 AW235763 AA927051 AI862075 BE886691 BE619282
414770 41721.1 AK056926 BG473673 BG482256 AL135566 AW419211 BF949370 AL120313 AV703730 H82569 BG012696 R27084 AA304583 BM452908
BF516419 BF515687 BG036572 BG696740 AW953552 AW859437 AA306038 AI754064 AA608729 AA664163 H65119 AW272606
BF942099 AW130468 BI089467 BG821499 AA152403 BF310450 BF314240 BG830310 BF803223 BG764269 BE542645 BE259142 R26953
BE257224 BG475461 BF677821 R33048
438714 2576235.1 AA814859 AI582623 AA814857
432339 57992.1 BG823745 AW411259 BG111139 BM041741 AW015049 AW068953 AW014085 AA969360 A1027260 AI948416 AW015886 AA918278
AA705292 AA702483 AA534205 BE856934 AI129462 BE926765 AI684275 R52686 N34869 H23555
438869 52134.1 AF075009 R63109 R63068
431912 610.10 BI763666 BI517886 BI759051 AI688604 AI660552 BF588523 AW004785 AW295479 BF591117 BF002672 BF064073 AA594441 AI38034O
AI700219 AI659950 AI688540 AW296326
450251 40382.4 BE080483 A16B9298 BE080416
412452 71091.1 BE796667 BF330981 BE394193 Z45547 BG490525 F35734 AA130708 AA577072 AA446587 AA215665 AA978209 BG740729 BG746810
BE298184 AI356291 AI671975 AI818924 AV715722 AI078381 BI142391 AI201085 AI198283 A1077572 AI694848 AW016425 BM456416
AI277223 AW771476 F26140 AA102778 AW025780 R44726 AA761079 AI581346 AI991909 BM005939 BE537999 BG469717 AA114156
BF437200 BE774942
418259 133853.1 BM310925 AA426110 BM310629 BF434286 AW015091 BF475996 AW118867 BE675186 AI688568 AI453594 AW590589 AI652425
AI827969 BF056946 AI802866 AI393380 AI476224 AW590639 AW136271 AI458252 AI524726 AA843768 AA782158 AI336058 AI097532
AW451563 AA459408 AA459633 AA418444 W23607 BG940150 AI493445 AW054729 AI221929 AI868744 AA215405 AA766713 AA621546
BF928317 BE464132 AI990909 AW271459 A1262061 AA215404 N74332 BG940151 BG952261 AA972115 W96315 AA689586 R69057
BF766886 BE769254 W05240
452279 11990 AF392454 AK023074 A1884890 AI814455 AW966220 BF736545 AA026021 AA286843 AA251918 BG197710 AA026294 AA337356
BC010422 AK023226 NM.022776 BM459496 AA769310 AI826460 AU153650 AU160375 AW166211 AW292992 BF433538 AI823888
AI684798 AI655985 AW770982 AI400454 AI276257 AA639510 AI689818 AW772604 AA807639 AU130298 AU132028 BF900889 BF904822 AY007102 AU143256 BG621460 AA829630 AI864665 AI084922 AA025234 AI360060 AA766554 AA026295 AA825817 AA251762 BE180751 BM464530 AV715833 AA779447 AI452519 AW418525 AA435643 D25894 AA435651 AA286844 N64369 AI702262 BG288063 BE170545 BM466232 BE299160 AA169573 AL567428 BF217285 BE967276
449230 6182.6 BC006329 AK026224 BG105365 AI472084 AW074277 AI743908 BM309990 BI850432 AI094365 AI539568 AW779999 AI261365 AA988975
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456381 2502811 AA236606 AA237079 AA459341
412636 14381 M77830 NM.004415 AF139065 BG681115 BG740377 BI712964 BG000656 AA128470 BI438324 H27408 BE931630 BE167165 AW370827
AW370813 J05211 BG698865 BG740734 BG680618 BG739778 BI765807 BM353403 BM353248 AW177784 AW205789 AW951576
AW848592 BE182164 BF149266 BE940187 BI060445 BI060444 BF350983 BE720095 BE720069 BE715154 BE082584 BE082576
BE004047 AA857316 BI039774 BE713818 BE713548 AW170253 BE160433 BI039775 AW886475 BM462504 BE931734 BF149264
AA340777 BF381183 BG621737 AU127260 AW364859 BF993352 BG223489 BE819009 BF381184 BE715956 R58704 AA852212
AW366566 BI090358 BF087707 BE819046 BE819005 AA377127 BE073467 BE819069 BE819048 BI036306 BG990973 BI040954
BF919911 AU140155 AI951766 AI434518 AW804674 BF752969 BE837009 BE925826 BF149265 AW995615 BE814264 BI039782
AU140407 BE144243 BE709863 BF985642 BE001923 BF933510 AW265328 BG436319 BE182166 AW365175 AW847688 BE818280
AW177933 BF873679 AW178000 BE082526 BF476866 BF086994 BF592276 BE082507 BE082514 BE082505 BF873693 AW068840
AW847678 BF804153 AW365157 BE813930 BE002030 AW365153 BE184941 BF749421 BE184920 BF839562 BE184933 BF842254
BE698470 BE931048 BF999889 BF368816 BE184924 BE159646 BE714632 BE184948 BG986845 AA131128 AA099891 W39488 C04715
BF096124 BE865341 AW799304 AL603116 BE149760 BE705967 BE705966 BE705968 AW848723 AW376699 AW376817 AW376697
BG005097 BF751115 BE696084 AW848371 AW376782 AW848789 AW849074 AW361413 BF927725 BF094211 AW997139 BE865474
BE185187 BE156621 BE715089 BE713297 BE713298 BE179915 AW799309 BF872345 BF088676 BE705939 AW752599 BG005197
BF350086 BE715196 BE715155 BF752396 BF093817 BF831190 BF752409 BE006561 BG959922 BF094833 BF094748 BF094583
AW377699 AW607238 BE082519 AW377700 BF349467 AH 90590 AI554403 AI392926 AU158477 BI467252 AU159919 A1760816 BF082516
AI439101 AA451923 AI340326 AI590975 BI791553 AI700963 AI142882 AA039975 AA946936 AA644381 BM314884 AA702424 AI417612
AW190555 AI220573 AI304772 AI270345 AI627383 AA552300 AI911702 AW166807 A1346078 W95070 AA149191 AA026864 AI830049
AW780435 AI078449 AI819984 AI858282 BI468588 AI860584 AI025932 AA026047 AA703232 AA658154 AA515500 AW192085 AA918281
T77861 AI927207 AI205263 BF082491 AW021347 A1568096 BE939862 AA088866 D12062 AA056527 AA782109 W19287 W02156
AW150038 AA022701 T87181 H44405 AI910434 BF082513 AI494069 AI270027 AI635878 AA128330 BG681425 BE706078 R20904
BG680059 BG676647 BF764409 AA026654 AV745530 BI762796 BG287391 AW798780 BE706045 BE926470 AW799118 BF087996
BE002273 AW879451 AI571075 BE067786 AV721320 AI022862 N29754 C03378 N84767 AA131077 H30146 BE714290 AI686869
AI568892 A1915596 AW105614 AI887258 AI538577 BE926474 BE067737 BG319486 AA247685 AW798883 AW103521 BF989173
AW860878 BE939707 BE185750 BE714064 BE713903 BE713868 BE713763 BG950164 BE713810 AW365151 BG955489 BE005272
BF915937 AW365148 AI905927 BF992780 AW853812 BG954443 BI770853 BG679406 BG740832 BG681087 BG698430 AA455100
T87267 BE696209 BE696210 BI089483 BE006273 BE872225 AW391912 BE925515 BG677012 BG741970 AA026480 BE705999
BG677157 BE009090 BG681378 BE712291 BG961498 BG678984 BI040941 AA337270 AW384371 AW847442 BI058659 BE813665
W95048 W25458 AW177786 AA025851 BE931733 BF154837 BG949393 BE714441 AW996245 BE711801 AI284090 BE064323 BE719390
BE940148 BG991212 BF375714 BF349522 BG996267 T48793 BI013292 BE001925 AW365156 AW365154 AW606653 BF763109
BE931637 BE167181 BE713879 BF354008 BF678726 H90899 AW365145 W38382 AI498487
454516 1058492.1 AW803413 AW803403 AW803466 AW803268 AW803341 AW803402 AW803334 AW803355 AW803265 AW803414 AW803396
447782 23929611 W29040 AI668903 AI424446
413645 12343451 AA130992 AW969537 AA503835
410840 1061234.1 AW806924 AW866478 AW866473 AW866390 AW866309 BF373982 AW866298 AW866539 AW866521 AW866547 AW866454 AW866537
AW866517 BF373957 BF373949 AW866403 AW866369
437818 25120631 AA769054AA778197
406687 00 M31126
400133 23681 NM.005648 BC013809 L34587 BF103775 BG702618 BG716553 B1667090 BG505863 BF983483 BG718195 BI857891 BG501016
BM043599 AL521812 BG705730 BI495545 BI495546 BF112248 BM023182 BM023123 AI075173 AW051799 BF058224 BI324885
BF436008 AA398446 BG822375 BM019558 BM023382 BG164174 N56909 BI467064 BM023464 AI207475 BM311415 BG758430
BG758807 AI934826 N90351 BG422026 BE910312 AI027778 AI081950 AI360890 BM0O9115 AH91829 BG759697 AH38728 AA399403
AI355589 AI336427 AA868702 AA393660 AA025127 BG027630 AA962774 AA631224 BG940967 BE791087 AA573315 W81685 AA393525
BG944103 AI339125 AH49864 AA977655 N90314 BE612839 BG491847 AH29091 AA461234 AA781198 AA759256 AA888954 AA975844
AI184099 AI018025 AA398363 A1003331 AH93380 AA626020 AI244476 AI601114 AW135664 AI206607 AW263599 AA813219 AI684453
AA878626 AA772222 AI085496 AI630226 BG940966 AI022010 AA770649 AA887624 AA491739 AA974295 BG530040 AA037091
AA019912 BI160457 H64512 BG503896
400219 BC003552 L10284 NM.001746 AJ271880 BI834281 BI597016 AU133331 BI668332 BI463073 BG720694 AL046729 BI460138 BI461052
AV647588 BG823268 AW889757 BE001258 AA312566 AA476446 AU098976 AA312196 BF749977 M94859 AF070646 BG564196
BG623597 AU117332 BG680963 BI667083 AU134542 AU138830 AI761759 BG679882 AA209406 AW512644 AW514813 AI570535
BE547592 BG655418 AI459204 BF725673 BE870032 BF001968 AL047245 BF724470 BF058818 H18415 BE076849 BE076857 BE076848
BE076827 BE076856 AV708687 AA380923 BE076851 F08118 L18887 BF795701 AU128383 BE908383 AW673350 AW500108 BE079837
BE929419 BF868758 AW503373 AW580528 BE005524 BI917505 BI457781 BE883812 BI668159 AA213643 AA374821 BF969974
BM480200 AU136152 BE395635 AV685066 AV693755 AL040984 AA676820 BG896408 BE082272 BE082312 C05287 BE082264
AA379850 AW672902 AI625955 BF033526 AW296557 AA728815 BE077058 AW081700 AA911707 AA362640 BE707179 BG913228
BG116191 BG752367 AA074678 AL036937 BG113760H03524 BG681802AI564688AU149556 BE178600AI813488 AI452433 Ai208989
AA599392 AA580385 AA486274 AA629899 AA565929 AA114046 AA094252 BM450328 BG529968 R68320 BE076792 BE090073
BE076855 BE076859 BE076829 AA361719 AA379164 AI202712 BG223315 BE122741 BG534531 AA903494 H24978 BF032674 BF085150
BE739158 AA352904 C21593 BG697597 AA134969 AA374612 BE566182 BE871838 BE076911 AW579175 BF966390 BI548594 BG386452
BG913195 BM456787 N40286 T80096 N39642 H42119 BG483861 AW381621 R69347 AW128895 AI367416 AI095285 AA099344
BE568161 AA180109 BF246488 BI561938 AW579170 BG567212
412999 1343220.1 BE046255 BE046611 BE046716 BE046732 BE046273
421258 266882.1 AA286731 AA287621 AW188228 AW137774 BF902638
414390 2128.2 BC022204 AK027690 NM 032839 BI765386 BE903404 BG700172 BF701671 BG252600 W60255 AW301576 W01296 AV724003
BE999965 AI949788 BM040799 Z43693 BF082768 BF328302 H09192 BF332781 R34999 BG573394 N57281 BE009522 BE281040
458215 540112.3 BE176902 BE177058 445511 9560.I BM471219 BE093160 BG171761 BI254009 AI905474 AA453162 AA829759 AI086559 AA776022 AI377446 BF589018 AA452822
AW614566 AA443880 AA476733 AW970674 AI393291 AA988283 AI905528 AW384956 D78656
452470 406524 AI903246 AI903467 AI903463 AI903248 AI903465 AI903243
439932 2601510.1 AI589851 AI741578 AI359930 AI820062 AI742528 AA854682 AI038485
449016 1500732.1 BE616111 BE081323 BE615864
423077 147641.1 AW964587 BF737224 AA321699 AV740801 BI005365 N44978
459234 14095.-17 AI940425
413402 151905.1 T24065 BE092516 BE091995 BE092527 BE092284 BE092271 BE092204 BF332633 BE092280 BE092202 BE091991 BE091994 BF742886
BF332627 BF332636 BE092068 BF742885 BE092063 BE092528 BE092447 BE092065 BE092283 BE092514
432492 715602.1 AW275110AA551054 AW867407 AW867499 BF374039
458422 4340.3 NM.006260 BE048475 AW080036 AA287317 AA400028 AI204437 AI830642 AA644420 AW614662 AW261942 U28424 BG335330
AU148480 AI095508 BF727387 BG256497 AI521859 AW291686 AW007816 BG002833 AA853075 AA779079 BF082050 AI640393
AA522954 T55310 AW517649 AA127463 AA887984 AW206341 BE858004 AW772531 AA604169 H83777 BG290990 AI692188 AI223311
AI708839 D82262 AA600260 AI364786 AA471007
434636 15423.1 AJ420454 AF147430 AA910497 BF432963 AI701451 AI743089 AA429326 AI887812 AA315932 AI005464 AL043321 AI300993 AA425105
BE467230 BE669770 AA885637 BE503044 AW014324 AI809584 AW167510 AA921331 AA903224 W01644 AI762128 AA031404 BE550653
AI694045 BE043088 BE670430 AI630969 AI457315 BE644737 BE327316 AW295247 N92784 AI630807 BE328180 AI269949 AW245292
AA083765 AA256898 AI375535 AA430673 AH68735 A1589717 AA015942 AI693885 AW341205 AA931651 BF856764 BE468094 BF433393
BF445511 AA928976 AI817684 BF111008 AA428316 AA455858 N25716 AA568727 AI581817 AA427482 H40678 AA041483 N71630
H51826 BF969052 AA094470 AI560352 T98937 W52816 AA083764
456487 AF064804 AA903211 AA829283 W05727 T30970 T32140 AI798807 BG218634 AW070452 AI767005 BF197394 BG202323 BG190077
AA013172 T98542 AL567878
TABLE 12C
Pkey Unique number corresponding to an Eos probeset
Ref Sequence source The 7 digit numbers In this column are Genbank Identifier (GI) numbers ' Dunham I et al " refers to the publication entted "The DNA sequence of human chromosome 22 ' Dunham I etal , Nature (1999) 402489-495 Strand Indicates DNA strand from which exons were predicted
Nt_posιtιon Indicates nucleotide positions of predicted exons
Pkey Ref Strand NLpositlon
401451 6634068 Minus 119926-121272
405770 2735037 Plus 61057-62075
401197 9719705 Plus 176341-176452
401519 6649315 Plus 157315-157950
406399 9256288 Minus 63448-63554
401866 8018106 Plus 73126-73623
404568 9966995 Minus 92893-93116
404561 9795980 Minus 69039-70100
403485 9966528 Pius 2888-3001,3198-3532,3655-4117
402812 6010110 Plus 25026-25091,25844-25920
401464 6682291 Minus 170688-170834
406181 5923650 Plus 16586-16855
404996 6007890 Plus 37999-38145,38652-38998,39727-39872,4055
402802 3287156 Minus 53242-53432
402408 9796239 Minus 110326-110491
402053 8083229 Plus 62703-63179
401558 7139678 Plus 103510-104090
402496 9797769 Minus 8615-9103
404704 9800728 Minus 88841-89018
403127 9211333 Minus 123813-124035
404632 9796668 Plus 45096-45229
404571 7249169 Minus 112450-112648
402114 8318586 Plus 71578-71715
405204 7230116 Plus 126569-126754
402855 9662953 Minus 59763-59909
403817 8962065 Plus 110297-111052
406081 9123861 Minus 38115-38691
406304 8575869 Plus 98839-98943,105865-106005
400884 9958187 Minus 57979-58189
404995 6006247 Minus 154015-154123
400583 9887611 Minus 201148-201272
402537 9801061 Minus 111945-112220,112466-112741
401560 8122921 Plus 94912-95082
404148 9863703 Plus 78218-78418,79571-79709
404891 7329392 Plus 84974-85125
403416 9438737 Plus 21296-21453
405031 7533980 Plus 142468-142830
401216 8077122 Minus 154722-154944
403851 7708872 Plus 22733-23007
401203 9743387 Minus 172961-173056,173868-173928
404440 7528051 Plus 80430-81581
405942 6758796 Minus 17579-18157
403011 6693597 Minus 3468-3623
403882 7710258 Plus 6080560997,62455-62559
403532 8076842 Minus 8175081901
401435 8217934 Minus 54508-55233
400965 7770576 Minus 173043-173564
402025 7547159 Plus 173835-173998
404173 9930908 Minus 51303-51635
404819 4678240 Plus 16223-16319,16427-16513,16736-16859,1694
402270 3108020 Plus 117656-117822 404607 7328770 Plus 28477-28591
405366 2182280 Plus 22478-22632
404624 9796168 Minus 92857-93081
404901 7331453 Plus 22679-22837,27864-28108
406137 9166422 Minus 30487-31058
406303 8575868 Plus 173622-173786
403848 7708855 Minus 26695-26912
402261 2887496 Plus 2872-3032,4673-4847,12749-12886
400821 8570338 Plus 7188-7393
400857 9739340 Minus 44729-44873
403671 7272159 Plus 104461-104701
402280 2795792 Plus 16831-17570
405976 8247789 Minus 126103-126874
406203 7289992 Minus 82220-82639
402609 9926446 Minus 113464-113633,114264-114654
402927 8217647 Minus 47247-47396
403324 8440025 Minus 107104-107309
400528 6981824 Plus 472381-472528,474170-474277,475328-47554
404478 8096498 Minus 65417-65625
402265 3287673 Plus 21059-21168
401796 7321653 Minus 36356-36533
401783 7249190 Plus 139369-139827,140509-140591,140834-14099
402553 9863566 Plus 48292-48398,49564-49944
405558 1621110 Plus 4502-4644,5983-6083
404576 4020145 Plus 17309-17938
401924 3892083 Minus 129614-129831,130489-130614,130696-13085
406389 9256209 Minus 48376-48504,50635-50763,52935-53063,5601
404156 9886577 Plus 127319-127754
404580 6539738 Minus 240588-241589
405418 6997292 Plus 51839-51953
403291 7230870 Plus 95177-95435
400995 8099094 Plus 141186-141601
405357 2133873 Minus 4536-4604,5297-5392
403055 8748904 Minus 109532-110225
402102 8117771 Minus 174566-174740
401759 9929699 Plus 59811-60665
405510 7630909 Minus 101028-101174
402842 9369121 Minus 76355-76479
401696 3417290 Minus 46209-46401
405484 5922025 Plus 199214-199579,199672-199920,200262-20049
405010 6094622 Plus 28830-29050
405704 4204244 Plus 138842-139051
403167 9838127 Plus 162599-162935
405276 4079595 Minus 40060-40215
403349 8569773 Minus 167815-168374
405451 7622517 Minus 145949-146227
403961 7596976 Minus 110393-110603
405863 7657810 Plus 49410-49620
405258 7329310 Plus 129930-130076
402412 7408036 Plus 75075-75679
400567 9884730 Plus 72252-72396
404109 9211742 Minus 144675-144928,151899-152064
405723 9801668 Plus 114896-115831
404120 7342152 Plus 135775-136000
402285 2689079 Minus 92386-92634
400817 8569994 Plus 170793-170948
402505 9797871 Plus 27326-28231
405215 7230201 Minus 61683-61808
402008 6630597 Plus 164419-164809
405387 6587915 Minus 3769-3833,5708-5895
405573 3820491 Minus 32645-33144
402663 8077020 Minus 14155-14364
401917 9502466 Plus 25054-25229
404494 8151634 Minus 53604-53893
400639 9887597 Plus 23150-23580
405705 4165009 Plus 120228-120800
404423 7407959 Plus 34438-34618
401913 9369520 Minus 33753-33904
405028 7533974 Minus 110588-110847,110933-111115
402189 8576043 Minus 128318-129601
401804 7331475 Minus 154865-155024
402229 9965022 Minus 15739-15951,16166-16779
404877 1519284 Plus 1095-2107
404341 7630856 Minus 13527-14130
401160 6067118 Minus 8280-8945
401925 3892083 Minus 138252-138469,140239-140364,140437-14059
406374 9256132 Plus 58991-59137
402530 7630937 Minus 1524-2003
403332 8568139 Minus 31409-31674
401952 3319121 Minus 53770-53979
402819 6729581 Plus 29217-29422
402014 7417799 Plus 36641-37171
403549 8081591 Minus 137150-137362
403481 9965004 Plus 93496-93633
401438 4885691 Minus 72461-72605
403429 9719566 Minus 52789-52917 403154 7407986 Minus 14228-14736
403858 7708944 Plus 37262-37517
400540 7574902 Plus 116601-116700,119129-119312,122026-12218
401403 7710966 Plus 146180-146294
406423 9256411 Plus 165600-165824
401711 6682593 Minus 19740-19938
402942 9368398 Plus 102152-102386
401138 2547238 Plus 3897-4121
406237 7417725 Plus 30032-30501
402322 7630359 Minus 75078-75203
404661 9797073 Plus 33374-33675,33769-34008
405673 4589984 Plus 50700-50842
405869 6758731 Minus 89867-90358
406261 5686411 Minus 9906-10594
401708 2951946 Plus 154511-155298
402704 8782736 Plus 37368-37493
400987 8086488 Minus 22052-22185
404029 7671252 Plus 108716-111112
406596 8248613 Minus 128312-128539
405850 6164995 Plus 13871-14110
404745 6981829 Plus 101968-102920
401908 8698760 Minus 126888-127024
405365 2275192 Minus 119867-120372,120481-120824,121029-12135
405883 6758747 Plus 60621-61193
401095 9965511 Plus 140224-140501,141208-141373
402840 9369121 Minus 57118-57306
406255 7417729 Plus 2959-3200
404306 5679453 Plus 32024-32174,32823-32927
404053 3548785 Plus 61797-64205
400834 8705192 Plus 121963-122288
401192 9719502 Minus 69559-70101
405760 6066938 Minus 37424-38045
404071 7210053 Minus 167354-167859,168810-168920,169000-16910
404754 7637341 Plus 57788-57931,59369-59525,77040-77131,7930
405710 5531256 Minus 66203-66832
405779 7280331 Minus 33048-33856
400880 9931121 Plus 29235-29336,36363-36580
405697 4309923 Minus 56765-57010,57696-58016
401898 8570008 Minus 72013-72132,72400-72487
403509 7630896 Plus 144706-144901
401463 6682291 Minus 163135-163262
400730 8118960 Plus 11434-11748
403794 8096910 Plus 163292-163884
404496 8151634 Plus 145065-145179
400547 9801025 Plus 41505-42032
406542 7711499 Plus 117335-118473
401405 7768126 Minus 69276-69452,69548-69958
400845 9188605 Plus 34428-34612
403935 7454203 Plus 16955-17310
404705 9800794 Minus 75671-75910
404592 9943965 Minus 39067-39225
402239 7690131 Plus 38175-38304,42133-42266
402889 9931133 Plus 89392-89498,90358-90571
400750 8119067 Plus 198991-199168,199316-199548
It is understood that the examples described above in no way serve to limit the true scope of this invention, but rather are presented for illustrative purposes. All publications, sequences of accession numbers, and patent applications cited in this specification are herein incorporated by reference as if each individual publication or patent application were specifically and individually indicated to be incorporated by reference.

Claims

WHAT IS CLAIMED IS:
1. A method of detecting a metastatic breast cancer or metastatic lung cancer-associated transcript in a cell, the method comprising contacting a biological sample with a polynucleotide that selectively hybridizes to a nucleic acid sequence at least 80% identical to a sequence selected from those listed in Tables 1-12.
2. The method ofclaim 1, wherein the metastatic cancer-associated transcript is a metastatic lung cancer-associated transcript.
3. The method ofclaim 1, wherein the metastatic cancer-associated transcript is a metastatic breast cancer-associated transcript.
4. The method ofclaim 1, wherein the biological sample comprises isolated nucleic acids.
5. The method of claim 1 , wherein the polynucleotide or the biological sample is labeled.
6. The method of claim 1 , wherein the polynucleotide is immobilized on a solid surface.
7. An isolated nucleic acid molecule consisting of a polynucleotide sequence selected from those listed in Tables 1-12.
8. An expression vector comprising the nucleic acid of claim 7.
9. A host cell comprising the expression vector of claim 8.
10. An isolated polypeptide which is encoded by a nucleic acid sequence selected from those listed in Tables 1-12.
11. An antibody that specifically binds a polypeptide of claim 10.
12. The antibody of claim 11 , wherein the antibody is an antibody fragment.
13. The antibody ofclaim 11, wherein the antibody is a humanized antibody
14. A method of detecting a metastatic breast cancer or metastatic lung cancer cell in a biological sample, the method comprising contacting the biological sample with an antibody of claim 11.
15. The method ofclaim 14, wherein the antibody is labeled.
16. A method of detecting antibodies specific to metastatic breast cancer in a patient, the method comprising contacting a biological sample from the patient with a polypeptide encoded by a nucleic acid comprising a sequence selected from those listed in Tables 1A-5C, 11 A-12C.
17. A method of detecting antibodies specific to metastatic lung cancer in a patient, the method comprising contacting a biological sample from the patient with a polypeptide encoded by a nucleic acid comprising a sequence selected from those listed in Tables 6A-12C.
18. A method for identifying a compound that modulates a metastatic breast cancer-associated polypeptide, the method comprising the steps of: (i) contacting the compound with a metastatic breast cancer-associated polypeptide, the polypeptide encoded by a polynucleotide that selectively hybridizes to a nucleic acid sequence at least 80% identical to a sequence selected from those listed in Tables 1A-5C, HA-12C; and (ii) determining the functional effect of the compound upon the polypeptide.
19. The method ofclaim 18, wherein the functional effect is determined by measuring ligand binding to the polypeptide.
20. A method for identifying a compound that modulates a metastatic lung cancer-associated polypeptide, the method comprising the steps of: (i) contacting the compound with a metastatic breast cancer-associated polypeptide, the polypeptide encoded by a polynucleotide that selectively hybridizes to a nucleic acid sequence at least 80% identical to a sequence selected from those listed in Tables 6A-12C; and (ii) determining the functional effect of the compound upon the polypeptide.
21. A method of inhibiting proliferation of a metastatic breast cancer - associated cell in a patient, the method comprising the step of administering to the subject a therapeutically effective amount of a compound that modulates a polypeptide encoded by a nucleic acid sequence selected from those listed in Tables 1 A-5C, 11 A-12C.
22. A method of inhibiting proliferation of a metastatic lung cancer - associated cell in a patient, the method comprising the step of administering to the subject a therapeutically effective amount of a compound that modulates a polypeptide encoded by a nucleic acid sequence selected from those listed in Tables 6A-12C.
23. A drug screening assay comprising the steps of (i) administering a test compound to a mammal having metastatic breast cancer or a cell isolated therefrom; (ii) comparing the level of gene expression of a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence selected from those listed in Tables 1 A-5C, 11A-12C in a treated cell or mammal, with the level of gene expression of the polynucleotide in a control cell or mammal, wherein a test compound that modulates the level of expression of the polynucleotide is a candidate for the treatment of metastatic breast cancer.
24. A pharmaceutical composition for treating a mammal having metastatic breast cancer, the composition comprising a compound identified by the assay of claim 23 and a physiologically acceptable excipient.
25. A drug screening assay comprising the steps of (i) administering a test compound to a mammal having metastatic lung cancer or a cell isolated therefrom; (ii) comparing the level of gene expression of a polynucleotide that selectively hybridizes to a sequence at least 80% identical to a sequence selected from those listed in Tables 6A-12C in a treated cell or mammal, with the level of gene expression of the polynucleotide in a control cell or mammal, wherein a test compound that modulates the level of expression of the polynucleotide is a candidate for the treatment of metastatic lung cancer.
26. A pharmaceutical composition for treating a mammal having metastatic lung cancer, the composition comprising a compound identified by the assay of claim 25 and a physiologically acceptable excipient.
27. A method of detecting a metastatic breast cancer-associated polypeptide in a cell, the method comprising contacting a biological sample from the patient with a antibody that that specifically binds a polypeptide encoded by a polynucleotide sequence selected from those listed in Tables 1 A-5C, 11A-12C.
28. The method of claim 27, wherein the antibody is labeled.
29. A method of detecting a metastatic lung cancer-associated polypeptide in a cell from a patient, the method comprising contacting a biological sample from the patient with a antibody that that specifically binds a polypeptide encoded by a polynucleotide sequence selected from those listed in Tables 6A-12C.
30. The method of claim 29, wherein the antibody is labeled.
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Cited By (114)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2005040811A1 (en) * 2003-10-15 2005-05-06 Roche Diagnostics Gmbh Use of protein tip47 as a marker for breast cancer
WO2006049868A1 (en) * 2004-10-28 2006-05-11 Abbott Laboratories Nucleic acid primers and probes for detecting breast cells
WO2006060533A2 (en) 2004-12-01 2006-06-08 Genentech, Inc. Conjugates of 1, 8-bis-naphthalimides with an antibody
WO2006061430A2 (en) * 2004-12-10 2006-06-15 Proskelia Bone metastasis markers as a target regulating bone metastasis and bone development
EP1862556A1 (en) * 2006-06-02 2007-12-05 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for identifying genetic markers for secondary tumors and means for the identification, labelling and targeting of secondary tumors
US7488813B2 (en) 2005-02-24 2009-02-10 Compugen, Ltd. Diagnostic markers, especially for in vivo imaging, and assays and methods of use thereof
EP2126577A1 (en) * 2007-03-29 2009-12-02 Fujirebio Diagnostics, Inc. Use of he4 for assessment of breast cancers
EP2136820A1 (en) * 2007-03-05 2009-12-30 The University Of Queensland A target for breast cancer therapy and/or diagnosis
EP2286844A2 (en) 2004-06-01 2011-02-23 Genentech, Inc. Antibody-drug conjugates and methods
WO2011031870A1 (en) 2009-09-09 2011-03-17 Centrose, Llc Extracellular targeted drug conjugates
WO2011056983A1 (en) 2009-11-05 2011-05-12 Genentech, Inc. Zirconium-radiolabeled, cysteine engineered antibody conjugates
EP2333112A2 (en) 2004-02-20 2011-06-15 Veridex, LLC Breast cancer prognostics
US8034920B2 (en) 1997-10-31 2011-10-11 Abbott Laboratories Nucleic acid primers and probes for detecting breast cells
WO2011130598A1 (en) 2010-04-15 2011-10-20 Spirogen Limited Pyrrolobenzodiazepines and conjugates thereof
WO2011156328A1 (en) 2010-06-08 2011-12-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
EP2402758A2 (en) 2005-09-19 2012-01-04 Veridex, LLC Methods and materials for identifying the origin of a carcinoma of unknown primary origin
EP2423333A1 (en) * 2006-08-25 2012-02-29 Oncotherapy Science, Inc. Prognostic markers and therapeutic targets for lung cancer
WO2012028703A1 (en) * 2010-09-02 2012-03-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for the prognosis of the progression of cancer
WO2012074757A1 (en) 2010-11-17 2012-06-07 Genentech, Inc. Alaninyl maytansinol antibody conjugates
WO2012153492A1 (en) * 2011-05-06 2012-11-15 Oncotherapy Science, Inc. Nptx2 as tumor marker and therapeutic target for cancer
WO2012155019A1 (en) 2011-05-12 2012-11-15 Genentech, Inc. Multiple reaction monitoring lc-ms/ms method to detect therapeutic antibodies in animal samples using framework signature pepides
EP2605016A1 (en) * 2011-12-14 2013-06-19 Philip Morris Products S.A. Biomarkers related to lung cancer
WO2013130093A1 (en) 2012-03-02 2013-09-06 Genentech, Inc. Biomarkers for treatment with anti-tubulin chemotherapeutic compounds
WO2014057074A1 (en) 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2014140174A1 (en) 2013-03-13 2014-09-18 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2014140862A2 (en) 2013-03-13 2014-09-18 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
WO2014159981A2 (en) 2013-03-13 2014-10-02 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
WO2015023355A1 (en) 2013-08-12 2015-02-19 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
EP2876445A1 (en) * 2013-11-22 2015-05-27 Institut de Cancérologie de l'Ouest Method for in vitro diagnosing and prognosing of triple negative breast cancer recurrence
WO2015095223A2 (en) 2013-12-16 2015-06-25 Genentech, Inc. Peptidomimetic compounds and antibody-drug conjugates thereof
WO2015095212A1 (en) 2013-12-16 2015-06-25 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
WO2015095227A2 (en) 2013-12-16 2015-06-25 Genentech, Inc. Peptidomimetic compounds and antibody-drug conjugates thereof
CN104781672A (en) * 2012-10-02 2015-07-15 斯弗因高泰克有限公司 A method for predicting the risk of getting cancer or diagnosing cancer in a female subject
US9089525B1 (en) 2011-07-01 2015-07-28 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for reducing glucose levels in a subject
US9090712B2 (en) 2001-08-29 2015-07-28 Pacific Northwest Research Institute Diagnosis of carcinomas
US9212228B2 (en) 2005-11-24 2015-12-15 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
WO2016040825A1 (en) 2014-09-12 2016-03-17 Genentech, Inc. Anthracycline disulfide intermediates, antibody-drug conjugates and methods
WO2016037644A1 (en) 2014-09-10 2016-03-17 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
WO2016040856A2 (en) 2014-09-12 2016-03-17 Genentech, Inc. Cysteine engineered antibodies and conjugates
WO2016090050A1 (en) 2014-12-03 2016-06-09 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
US9382318B2 (en) 2012-05-18 2016-07-05 Amgen Inc. ST2 antigen binding proteins
US9433675B2 (en) 2012-05-23 2016-09-06 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of cancer
EP3088004A1 (en) 2004-09-23 2016-11-02 Genentech, Inc. Cysteine engineered antibodies and conjugates
US9512232B2 (en) 2012-05-09 2016-12-06 Ganymed Pharmaceuticals Ag Antibodies against Claudin 18.2 useful in cancer diagnosis
US9605265B2 (en) 2009-03-16 2017-03-28 Atyr Pharma, Inc. Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
WO2017059289A1 (en) 2015-10-02 2017-04-06 Genentech, Inc. Pyrrolobenzodiazepine antibody drug conjugates and methods of use
WO2017064675A1 (en) 2015-10-16 2017-04-20 Genentech, Inc. Hindered disulfide drug conjugates
WO2017068511A1 (en) 2015-10-20 2017-04-27 Genentech, Inc. Calicheamicin-antibody-drug conjugates and methods of use
US9637730B2 (en) 2010-07-12 2017-05-02 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of histidyl-tRNA synthetases
US9770487B2 (en) 2013-02-20 2017-09-26 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic adenocarcinoma
WO2017165734A1 (en) 2016-03-25 2017-09-28 Genentech, Inc. Multiplexed total antibody and antibody-conjugated drug quantification assay
US9775785B2 (en) 2004-05-18 2017-10-03 Ganymed Pharmaceuticals Ag Antibody to genetic products differentially expressed in tumors and the use thereof
EP3235820A1 (en) 2014-09-17 2017-10-25 Genentech, Inc. Pyrrolobenzodiazepines and antibody disulfide conjugates thereof
WO2017201449A1 (en) 2016-05-20 2017-11-23 Genentech, Inc. Protac antibody conjugates and methods of use
WO2017205741A1 (en) 2016-05-27 2017-11-30 Genentech, Inc. Bioanalytical method for the characterization of site-specific antibody-drug conjugates
WO2017214024A1 (en) 2016-06-06 2017-12-14 Genentech, Inc. Silvestrol antibody-drug conjugates and methods of use
US9878008B2 (en) 2012-12-27 2018-01-30 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having bile acid diarrhea or bile acid malabsorption
WO2018031662A1 (en) 2016-08-11 2018-02-15 Genentech, Inc. Pyrrolobenzodiazepine prodrugs and antibody conjugates thereof
US9919056B2 (en) 2012-10-12 2018-03-20 Adc Therapeutics S.A. Pyrrolobenzodiazepine-anti-CD22 antibody conjugates
US9925242B2 (en) 2012-12-27 2018-03-27 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for treatment of nonalcoholic steatohepatitis
US9931414B2 (en) 2012-10-12 2018-04-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US9931415B2 (en) 2012-10-12 2018-04-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
WO2018065501A1 (en) 2016-10-05 2018-04-12 F. Hoffmann-La Roche Ag Methods for preparing antibody drug conjugates
US9943577B2 (en) 2009-12-11 2018-04-17 Atyr Pharma, Inc. Aminoacyl tRNA synthetases for modulating inflammation
US9950078B2 (en) 2013-10-11 2018-04-24 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US9956299B2 (en) 2013-10-11 2018-05-01 Medimmune Limited Pyrrolobenzodiazepine—antibody conjugates
US9963494B2 (en) 2012-11-28 2018-05-08 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for reducing glucose levels in a subject
US10010624B2 (en) 2013-10-11 2018-07-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10029018B2 (en) 2013-10-11 2018-07-24 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US10093735B2 (en) 2014-01-24 2018-10-09 Ngm Biopharmaceuticals, Inc. Beta-klotho binding proteins
US10093915B2 (en) 2013-03-15 2018-10-09 Atyr Pharma Inc. Histidyl-tRNA synthetase-Fc conjugates
US10093736B2 (en) 2012-11-13 2018-10-09 Biontech Ag Agents for treatment of claudin expressing cancer diseases
EP3388079A1 (en) * 2015-03-27 2018-10-17 Immatics Biotechnologies GmbH Novel peptides and combination of peptides for use in immunotherapy against various tumors (seq id 253 - rad54b)
US10137195B2 (en) 2013-03-18 2018-11-27 Ganymed Pharmaceuticals Gmbh Therapy involving antibodies against Claudin 18.2 for treatment of cancer
KR20180132817A (en) * 2016-04-06 2018-12-12 이매틱스 바이오테크놀로지스 게엠베하 Combinations of novel peptides and peptides for use in immunotherapy for AML and other cancers
US10196698B2 (en) 2013-01-23 2019-02-05 The Johns Hopkins University DNA methylation markers for metastatic prostate cancer
WO2019060398A1 (en) 2017-09-20 2019-03-28 Ph Pharma Co., Ltd. Thailanstatin analogs
US10369199B2 (en) 2013-10-28 2019-08-06 Ngm Biopharmaceuticals, Inc. Methods of using variants of FGF19 polypeptides for the treatment of cancer
US10392393B2 (en) 2016-01-26 2019-08-27 Medimmune Limited Pyrrolobenzodiazepines
US10398758B2 (en) 2014-05-28 2019-09-03 Ngm Biopharmaceuticals, Inc. Compositions comprising variants of FGF19 polypeptides and uses thereof for the treatment of hyperglycemic conditions
US10414824B2 (en) 2002-11-22 2019-09-17 Ganymed Pharmaceuticals Ag Genetic products differentially expressed in tumors and the use thereof
US10420777B2 (en) 2014-09-12 2019-09-24 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US10434144B2 (en) 2014-11-07 2019-10-08 Ngm Biopharmaceuticals, Inc. Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders
US10456449B2 (en) 2014-06-16 2019-10-29 Ngm Biopharmaceuticals, Inc. Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
US10517929B2 (en) 2014-10-23 2019-12-31 Ngm Biopharmaceuticals, Inc. Pharmaceutical compositions comprising FGF19 variants
US10543279B2 (en) 2016-04-29 2020-01-28 Medimmune Limited Pyrrolobenzodiazepine conjugates and their use for the treatment of cancer
US10544223B2 (en) 2017-04-20 2020-01-28 Adc Therapeutics Sa Combination therapy with an anti-axl antibody-drug conjugate
WO2020049286A1 (en) 2018-09-03 2020-03-12 Femtogenix Limited Polycyclic amides as cytotoxic agents
WO2020086858A1 (en) 2018-10-24 2020-04-30 Genentech, Inc. Conjugated chemical inducers of degradation and methods of use
WO2020123275A1 (en) 2018-12-10 2020-06-18 Genentech, Inc. Photocrosslinking peptides for site specific conjugation to fc-containing proteins
US10695433B2 (en) 2012-10-12 2020-06-30 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10695439B2 (en) 2016-02-10 2020-06-30 Medimmune Limited Pyrrolobenzodiazepine conjugates
WO2020157491A1 (en) 2019-01-29 2020-08-06 Femtogenix Limited G-a crosslinking cytotoxic agents
US10736903B2 (en) 2012-10-12 2020-08-11 Medimmune Limited Pyrrolobenzodiazepine-anti-PSMA antibody conjugates
US10744185B2 (en) 2015-11-09 2020-08-18 Ngm Biopharmaceuticals, Inc. Methods of using variants of FGF19 polypeptides for the treatment of pruritus
US10751346B2 (en) 2012-10-12 2020-08-25 Medimmune Limited Pyrrolobenzodiazepine—anti-PSMA antibody conjugates
US10780096B2 (en) 2014-11-25 2020-09-22 Adc Therapeutics Sa Pyrrolobenzodiazepine-antibody conjugates
US10800843B2 (en) 2015-07-29 2020-10-13 Ngm Biopharmaceuticals, Inc. Beta klotho-binding proteins
US10799595B2 (en) 2016-10-14 2020-10-13 Medimmune Limited Pyrrolobenzodiazepine conjugates
US11059893B2 (en) 2015-04-15 2021-07-13 Bergenbio Asa Humanized anti-AXL antibodies
US11066454B2 (en) 2012-11-28 2021-07-20 Ngm Biopharmaceuticals, Inc. Compositions comprising variants and fusions of FGF19 polypeptides
US11135303B2 (en) 2011-10-14 2021-10-05 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US11160872B2 (en) 2017-02-08 2021-11-02 Adc Therapeutics Sa Pyrrolobenzodiazepine-antibody conjugates
WO2022023735A1 (en) 2020-07-28 2022-02-03 Femtogenix Limited Cytotoxic agents
US11318211B2 (en) 2017-06-14 2022-05-03 Adc Therapeutics Sa Dosage regimes for the administration of an anti-CD19 ADC
US11352324B2 (en) 2018-03-01 2022-06-07 Medimmune Limited Methods
US11370801B2 (en) 2017-04-18 2022-06-28 Medimmune Limited Pyrrolobenzodiazepine conjugates
US11370841B2 (en) 2016-08-26 2022-06-28 Ngm Biopharmaceuticals, Inc. Methods of treating fibroblast growth factor 19-mediated cancers and tumors
US11517626B2 (en) 2016-02-10 2022-12-06 Medimmune Limited Pyrrolobenzodiazepine antibody conjugates
US11524969B2 (en) 2018-04-12 2022-12-13 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof as antitumour agents
US11612665B2 (en) 2017-02-08 2023-03-28 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US11649250B2 (en) 2017-08-18 2023-05-16 Medimmune Limited Pyrrolobenzodiazepine conjugates
US11702473B2 (en) 2015-04-15 2023-07-18 Medimmune Limited Site-specific antibody-drug conjugates
US11767520B2 (en) 2017-04-20 2023-09-26 Atyr Pharma, Inc. Compositions and methods for treating lung inflammation

Families Citing this family (67)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7129061B1 (en) * 1996-08-07 2006-10-31 Biogen Idec Ma Inc. Tumor necrosis factor related ligand
KR20010102978A (en) 1999-01-15 2001-11-17 아스트루 마이클 제이 Antagonists of tweak and of tweak receptor and their use to treat immunological disorders
US20030114410A1 (en) * 2000-08-08 2003-06-19 Technion Research And Development Foundation Ltd. Pharmaceutical compositions and methods useful for modulating angiogenesis and inhibiting metastasis and tumor fibrosis
US7208151B2 (en) * 2001-09-12 2007-04-24 Biogen Idec Ma Inc. Tweak receptor agonists as anti-angiogenic agents
SI1997512T1 (en) 2002-04-09 2014-03-31 Biogen Idec Ma Inc. Methods for treating TWEAK-related conditions
AU2005217646A1 (en) * 2004-02-26 2005-09-09 Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services A novel cofactor that modulates steroid receptor activities
JP2008522632A (en) 2004-12-13 2008-07-03 アレシア・バイオセラピューティクス・インコーポレーテッド Polynucleotide and polypeptide sequences involved in the process of bone remodeling
US20090124993A1 (en) 2005-02-17 2009-05-14 Burkly Linda C Treating neurological disorders
WO2006122187A2 (en) 2005-05-10 2006-11-16 Biogen Idec Ma Inc. Treating and evaluating inflammatory disorders
WO2006138219A2 (en) 2005-06-13 2006-12-28 Biogen Idec Ma Inc. Methods of diagnosis / prognosis of inflammatory conditions
EP1943341A4 (en) * 2005-09-27 2010-07-07 Ca Nat Research Council Blood-brain barrier epitopes and uses thereof
AU2006320699A1 (en) * 2005-12-01 2007-06-07 New York Blood Center, Inc. Peptide inhibitors of ABL kinases
US20090215642A1 (en) * 2005-12-09 2009-08-27 Knudson Alfred G Methods and Compositions for Assessing Alterations in Gene Expression Patterns in Clinically Normal Tissues Obtained from Heterozygous Carriers of Mutant Genes Associated with Cancer and Methods of Use Thereof
US20120208824A1 (en) 2006-01-20 2012-08-16 Cell Signaling Technology, Inc. ROS Kinase in Lung Cancer
WO2007090076A2 (en) * 2006-01-27 2007-08-09 Tripath Imaging, Inc. Methods for identifying patients with an increased likelihood of having ovarian cancer and compositions therefor
WO2008031910A2 (en) * 2006-09-15 2008-03-20 Proyecto De Biomedicina Cima, S.L. Experimental models for non-microcytic lung cancer metastasis to bone
EP2657705A3 (en) * 2006-09-19 2013-12-25 Metabolon Inc. Biomarkers for prostate cancer and methods using the same
US7951781B2 (en) * 2006-11-02 2011-05-31 University Of Iowa Research Foundation Methods and compositions related to PLUNC surfactant polypeptides
EP2129796B1 (en) * 2007-02-21 2013-10-23 Oslo Universitetssykehus HF New markers for cancer
WO2008116592A1 (en) * 2007-03-23 2008-10-02 F. Hoffmann-La Roche Ag Apex as a marker for lung cancer
US20090004658A1 (en) * 2007-04-30 2009-01-01 Jianhua Luo Integrin alpha 7 mutations in prostate cancer, liver cancer, glioblastoma multiforme, and leiomyosarcoma
JP5659014B2 (en) 2007-08-02 2015-01-28 ジリード バイオロジクス,インク. Methods and compositions for treatment and diagnosis of fibrosis, tumor invasion, angiogenesis and metastasis
CA2701945A1 (en) * 2007-10-22 2009-04-30 Samuel Norbert Breit Methods of prognosis of overall survival using mic-1
EP2060583A1 (en) * 2007-10-23 2009-05-20 Ganymed Pharmaceuticals AG Identification of tumor-associated markers for diagnosis and therapy
CA2706881A1 (en) 2007-11-30 2009-06-11 Brian Z. Ring Tle3 as a marker for chemotherapy
US20110091482A1 (en) * 2008-04-11 2011-04-21 The Regents Of The University Of Colorado, A Body Corporate Expression of kir in human cancer cells as a biomarker for immuno-escape and cancer metastasis
GB0808668D0 (en) * 2008-05-13 2008-06-18 Univ Aberdeen Materials and methods relating to a G-protein coupled receptor
US8686112B2 (en) * 2008-08-14 2014-04-01 Case Western Reserve University Methods and compositions for the detection of cancer
US10359425B2 (en) * 2008-09-09 2019-07-23 Somalogic, Inc. Lung cancer biomarkers and uses thereof
US20110105343A1 (en) * 2008-11-21 2011-05-05 Emory University Systems Biology Approach Predicts Immunogenicity of Vaccines
US9107935B2 (en) 2009-01-06 2015-08-18 Gilead Biologics, Inc. Chemotherapeutic methods and compositions
US9364477B2 (en) * 2009-02-12 2016-06-14 Cell Signaling Technology, Inc. Mutant ROS expression in human cancer
EP2270510A1 (en) * 2009-07-02 2011-01-05 EMBL (European Molecular Biology Laboratory) Diagnostic method for predicting the risk of cancer recurrence based on Histone macroH2A isoforms
WO2011022670A1 (en) * 2009-08-21 2011-02-24 Arresto Biosciences, Inc In vivo screening assays
MX2012002271A (en) * 2009-08-21 2012-07-20 Gilead Biologics Inc Therapeutic methods and compositions.
KR20120054077A (en) * 2009-08-21 2012-05-29 길리아드 바이오로직스, 인크. Methods and compositions for treatment of pulmonary fibrotic disorders
SG2014004816A (en) * 2009-08-21 2014-03-28 Gilead Biologics Inc Catalytic domains from lysyl oxidase and loxl2
JP2013502228A (en) * 2009-08-21 2013-01-24 ギリアド バイオロジクス,インク. In vitro screening assay
WO2011028819A1 (en) * 2009-09-01 2011-03-10 The Trustees Of Columbia University In The City Of New York Synergistic transcription modules and uses thereof
WO2011066380A1 (en) * 2009-11-25 2011-06-03 The Board Of Trustees Of The Leland Stanford Junior University Biomarkers for the diagnosis of kidney graft rejection
AR079217A1 (en) 2009-11-30 2012-01-04 Genentech Inc COMPOSITIONS AND METHODS FOR DIAGNOSIS AND TUMOR TREATMENT
CN102893157A (en) * 2009-12-22 2013-01-23 密执安大学评议会 Metabolomic profiling of prostate cancer
US8680246B2 (en) 2010-02-04 2014-03-25 Gilead Biologics, Inc. Antibodies that bind to lysyl oxidase-like 2 (LOXL2)
US20110229408A1 (en) * 2010-03-16 2011-09-22 Kenneth Ain Sodium-iodide symporter gene repressor binding site
US20110229878A1 (en) * 2010-03-16 2011-09-22 Kenneth Ain Human consensus sodium-iodide symporter repressor (nis-repressor) binding site
US20130230453A1 (en) * 2010-07-02 2013-09-05 Welcome Receptor Antibodies Pty Ltd Diagnosis and treatment of brain tumors
SG186953A1 (en) 2010-07-09 2013-02-28 Somalogic Inc Lung cancer biomarkers and uses thereof
CN106198980B (en) 2010-08-13 2018-09-07 私募蛋白质体公司 Cancer of pancreas biomarker and application thereof
US10047398B2 (en) 2010-10-06 2018-08-14 Fundacio Institut De Recerca Biomedica (Irb Barcelona) Method for the diagnosis, prognosis and treatment of breast cancer metastasis
WO2013011153A2 (en) 2011-07-21 2013-01-24 Fundació Institut D'investigació Biomèdica De Bellvitge (Idibell) Method for the prognosis and treatment of metastasis in breast cancer
RU2659423C2 (en) 2012-02-16 2018-07-02 ЭйТИР ФАРМА, ИНК. Hystidil-trna-synthetase for treatment of autoimmune and inflammatory diseases
EP2650682A1 (en) 2012-04-09 2013-10-16 Fundació Privada Institut de Recerca Biomèdica Method for the prognosis and treatment of cancer metastasis
DK2852399T3 (en) * 2012-05-21 2020-05-04 Univ Colorado Regents LEDGF PEPTIDES AND FORMULAS THEREOF FOR THE TREATMENT OF DEGENERATIVE DISORDERS
KR102175034B1 (en) * 2012-09-25 2020-11-06 유니버시티 오브 워싱턴 Desmoglein 2 (DSG2) Binding Proteins and Uses Therefor
JP6307519B2 (en) 2012-12-21 2018-04-04 メドイミューン・リミテッドMedImmune Limited Pyrrolobenzodiazepine and its conjugates
EA032986B1 (en) 2012-12-21 2019-08-30 Медимьюн Лимитед Pyrrolobenzodiazepines
US20140314792A1 (en) 2013-03-15 2014-10-23 Institució Catalana De Recerca I Estudis Avançats Method for the diagnosis, prognosis and treatment of cancer metastasis
JP2016538327A (en) 2013-09-24 2016-12-08 ユニバーシティ オブ ワシントン スルー イッツ センター フォー コマーシャリゼーション Desmoglein 2 (DSG2) binding protein and use thereof
US20150218643A1 (en) * 2014-02-06 2015-08-06 Brittany N. Lasseigne Differential methylation level of cpg loci that are determinative of kidney cancer
CN104360070B (en) * 2014-11-28 2017-02-22 山东新创生物科技有限公司 Application of peptidylarginine deiminase 2 (PAD2) to preparation of reagent for clinical blood diagnosis of tumors
AU2017271385B2 (en) 2016-05-25 2023-10-05 Inbiomotion S.L. Therapeutic treatment of breast cancer based on c-MAF status
US11879014B2 (en) 2017-03-17 2024-01-23 Tusk Therapeutics Ltd. Method of treating cancer or depleting regulatory T cells in a subject by administering a human IGG1 anti-CD25 antibody
US11654153B2 (en) 2017-11-22 2023-05-23 Inbiomotion S.L. Therapeutic treatment of breast cancer based on c-MAF status
TW202003034A (en) * 2018-03-13 2020-01-16 英商塔斯克療法有限公司 Anti-CD25 antibody agents
CN114231633B (en) * 2020-03-30 2022-05-20 中国医学科学院肿瘤医院 Application of exosomes ARPC5, STK3 and the like in lung cancer diagnosis
WO2022101906A1 (en) * 2020-11-15 2022-05-19 Ramot At Tel Aviv University Ltd. Method and pharmaceutical composition for inhibiting cancer metastasis
CN112964682B (en) * 2021-02-05 2022-02-25 中国科学院高能物理研究所 Method for visually and quantitatively marking aggregated functional protein in cells

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998055510A2 (en) * 1997-06-05 1998-12-10 Incyte Pharmaceuticals, Inc. Human ubiquitin carrier protein e2-like protein and cyclin b-like protein
WO2002010436A2 (en) * 2000-07-28 2002-02-07 The Brigham And Women's Hospital, Inc. Prognostic classification of breast cancer

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1998055510A2 (en) * 1997-06-05 1998-12-10 Incyte Pharmaceuticals, Inc. Human ubiquitin carrier protein e2-like protein and cyclin b-like protein
WO2002010436A2 (en) * 2000-07-28 2002-02-07 The Brigham And Women's Hospital, Inc. Prognostic classification of breast cancer

Cited By (190)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8034920B2 (en) 1997-10-31 2011-10-11 Abbott Laboratories Nucleic acid primers and probes for detecting breast cells
US9090712B2 (en) 2001-08-29 2015-07-28 Pacific Northwest Research Institute Diagnosis of carcinomas
US10414824B2 (en) 2002-11-22 2019-09-17 Ganymed Pharmaceuticals Ag Genetic products differentially expressed in tumors and the use thereof
WO2005040811A1 (en) * 2003-10-15 2005-05-06 Roche Diagnostics Gmbh Use of protein tip47 as a marker for breast cancer
EP2333112A2 (en) 2004-02-20 2011-06-15 Veridex, LLC Breast cancer prognostics
US9775785B2 (en) 2004-05-18 2017-10-03 Ganymed Pharmaceuticals Ag Antibody to genetic products differentially expressed in tumors and the use thereof
EP2286844A2 (en) 2004-06-01 2011-02-23 Genentech, Inc. Antibody-drug conjugates and methods
EP3088004A1 (en) 2004-09-23 2016-11-02 Genentech, Inc. Cysteine engineered antibodies and conjugates
WO2006049868A1 (en) * 2004-10-28 2006-05-11 Abbott Laboratories Nucleic acid primers and probes for detecting breast cells
WO2006060533A2 (en) 2004-12-01 2006-06-08 Genentech, Inc. Conjugates of 1, 8-bis-naphthalimides with an antibody
WO2006061430A2 (en) * 2004-12-10 2006-06-15 Proskelia Bone metastasis markers as a target regulating bone metastasis and bone development
WO2006061430A3 (en) * 2004-12-10 2006-08-03 Proskelia Bone metastasis markers as a target regulating bone metastasis and bone development
US7741433B2 (en) 2005-02-24 2010-06-22 Compugen Ltd. Diagnostic markers, especially for in vivo imaging and assays and methods of use thereof
US7488813B2 (en) 2005-02-24 2009-02-10 Compugen, Ltd. Diagnostic markers, especially for in vivo imaging, and assays and methods of use thereof
EP2402758A2 (en) 2005-09-19 2012-01-04 Veridex, LLC Methods and materials for identifying the origin of a carcinoma of unknown primary origin
US9212228B2 (en) 2005-11-24 2015-12-15 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US10174104B2 (en) 2005-11-24 2019-01-08 Ganymed Pharmaceuticals Gmbh Monoclonal antibodies against claudin-18 for treatment of cancer
US9751934B2 (en) 2005-11-24 2017-09-05 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US10017564B2 (en) 2005-11-24 2018-07-10 Ganymed Pharmaceuticals Gmbh Monoclonal antibodies against claudin-18 for treatment of cancer
US9499609B2 (en) 2005-11-24 2016-11-22 Ganymed Pharmaceuticals Ag Monoclonal antibodies against claudin-18 for treatment of cancer
US10738108B2 (en) 2005-11-24 2020-08-11 Astellas Pharma Inc. Monoclonal antibodies against claudin-18 for treatment of cancer
US11739139B2 (en) 2005-11-24 2023-08-29 Astellas Pharma Inc. Monoclonal antibodies against Claudin-18 for treatment of cancer
WO2007141046A3 (en) * 2006-06-02 2008-03-27 Fraunhofer Ges Forschung Method for identifying genetic markers for secondary tumors and means for the identification, labelling and targeting of secondary tumors
WO2007141046A2 (en) * 2006-06-02 2007-12-13 Fraunhofer Gesellschaft Zur Förderung Der Angewandten Forschung E. V. Method for identifying genetic markers for secondary tumors and means for the identification, labelling and targeting of secondary tumors
EP1862556A1 (en) * 2006-06-02 2007-12-05 Fraunhofer-Gesellschaft zur Förderung der angewandten Forschung e.V. Method for identifying genetic markers for secondary tumors and means for the identification, labelling and targeting of secondary tumors
EP2423333A1 (en) * 2006-08-25 2012-02-29 Oncotherapy Science, Inc. Prognostic markers and therapeutic targets for lung cancer
EP2423332A1 (en) * 2006-08-25 2012-02-29 Oncotherapy Science, Inc. Prognostic markers and therapeutic targets for lung cancer
AU2008222602B2 (en) * 2007-03-05 2013-06-20 The University Of Queensland A target for breast cancer therapy and/or diagnosis
EP2136820A4 (en) * 2007-03-05 2010-09-15 Univ Queensland A target for breast cancer therapy and/or diagnosis
US8431536B2 (en) 2007-03-05 2013-04-30 The University Of Queensland Target for breast cancer therapy and/or diagnosis
EP2136820A1 (en) * 2007-03-05 2009-12-30 The University Of Queensland A target for breast cancer therapy and/or diagnosis
EP2126577A1 (en) * 2007-03-29 2009-12-02 Fujirebio Diagnostics, Inc. Use of he4 for assessment of breast cancers
EP2126577A4 (en) * 2007-03-29 2010-06-02 Fujirebio Diagnostics Inc Use of he4 for assessment of breast cancers
US8455189B2 (en) 2007-03-29 2013-06-04 Jeffrey W. Allard Use of HE4 for assessment of breast cancers
US10017582B2 (en) 2009-03-16 2018-07-10 Atyr Pharma, Inc. Compositions and methods comprising histidyl-trna synthetase splice variants having non-canonical biological activities
US9605265B2 (en) 2009-03-16 2017-03-28 Atyr Pharma, Inc. Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
US11078299B2 (en) 2009-03-16 2021-08-03 Atyr Pharma, Inc. Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
US10941214B2 (en) 2009-03-16 2021-03-09 Atyr Pharma, Inc. Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
US10526419B2 (en) 2009-03-16 2020-01-07 Atyr Pharma, Inc. Compositions and methods comprising histidyl-tRNA synthetase splice variants having non-canonical biological activities
WO2011031870A1 (en) 2009-09-09 2011-03-17 Centrose, Llc Extracellular targeted drug conjugates
WO2011056983A1 (en) 2009-11-05 2011-05-12 Genentech, Inc. Zirconium-radiolabeled, cysteine engineered antibody conjugates
US9943577B2 (en) 2009-12-11 2018-04-17 Atyr Pharma, Inc. Aminoacyl tRNA synthetases for modulating inflammation
WO2011130598A1 (en) 2010-04-15 2011-10-20 Spirogen Limited Pyrrolobenzodiazepines and conjugates thereof
WO2011156328A1 (en) 2010-06-08 2011-12-15 Genentech, Inc. Cysteine engineered antibodies and conjugates
US9637730B2 (en) 2010-07-12 2017-05-02 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of histidyl-tRNA synthetases
US10196628B2 (en) 2010-07-12 2019-02-05 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of histidyl-tRNA synthetases
US10669533B2 (en) 2010-07-12 2020-06-02 Atyr Pharma, Inc. Innovative discovery of therapeutic, diagnostic, and antibody compositions related to protein fragments of Histidyl-tRNA synthetases
WO2012028703A1 (en) * 2010-09-02 2012-03-08 INSERM (Institut National de la Santé et de la Recherche Médicale) Method for the prognosis of the progression of cancer
WO2012074757A1 (en) 2010-11-17 2012-06-07 Genentech, Inc. Alaninyl maytansinol antibody conjugates
WO2012153492A1 (en) * 2011-05-06 2012-11-15 Oncotherapy Science, Inc. Nptx2 as tumor marker and therapeutic target for cancer
WO2012155019A1 (en) 2011-05-12 2012-11-15 Genentech, Inc. Multiple reaction monitoring lc-ms/ms method to detect therapeutic antibodies in animal samples using framework signature pepides
US11065302B2 (en) 2011-07-01 2021-07-20 Ngm Biopharmaceuticals, Inc. Compositions comprising fusion variants of FGF19 polypeptides
US10413590B2 (en) 2011-07-01 2019-09-17 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants of FGF19 polypeptides for reducing body mass in a subject
US9751924B2 (en) 2011-07-01 2017-09-05 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising fusion variants of FGF19 polypeptides for reducing glucose levels in a subject
US9670260B2 (en) 2011-07-01 2017-06-06 Ngm Biopharmaceuticals, Inc. Compositions comprising fusion variants of FGF19 polypeptides
US9089525B1 (en) 2011-07-01 2015-07-28 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for reducing glucose levels in a subject
US11135303B2 (en) 2011-10-14 2021-10-05 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
EP2605016A1 (en) * 2011-12-14 2013-06-19 Philip Morris Products S.A. Biomarkers related to lung cancer
WO2013130093A1 (en) 2012-03-02 2013-09-06 Genentech, Inc. Biomarkers for treatment with anti-tubulin chemotherapeutic compounds
US10053512B2 (en) 2012-05-09 2018-08-21 Ganymed Pharmaceuticals Ag Antibodies against claudin 18.2 useful in cancer diagnosis
US9512232B2 (en) 2012-05-09 2016-12-06 Ganymed Pharmaceuticals Ag Antibodies against Claudin 18.2 useful in cancer diagnosis
US9982054B2 (en) 2012-05-18 2018-05-29 Amgen Inc. ST2 antigen binding proteins
US9382318B2 (en) 2012-05-18 2016-07-05 Amgen Inc. ST2 antigen binding proteins
US10227414B2 (en) 2012-05-18 2019-03-12 Amgen Inc. ST2 antigen binding proteins
US11059895B2 (en) 2012-05-18 2021-07-13 Amgen Inc. ST2 antigen binding proteins
US10022444B2 (en) 2012-05-23 2018-07-17 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against Claudin 18.2 for treatment of cancer
US9433675B2 (en) 2012-05-23 2016-09-06 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of cancer
US10813996B2 (en) 2012-05-23 2020-10-27 Astellas Pharma Inc. Combination therapy involving antibodies against Claudin 18.2 for treatment of cancer
CN104781672A (en) * 2012-10-02 2015-07-15 斯弗因高泰克有限公司 A method for predicting the risk of getting cancer or diagnosing cancer in a female subject
US10335497B2 (en) 2012-10-12 2019-07-02 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US10799596B2 (en) 2012-10-12 2020-10-13 Adc Therapeutics S.A. Pyrrolobenzodiazepine-antibody conjugates
WO2014057074A1 (en) 2012-10-12 2014-04-17 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
EP2839860A1 (en) 2012-10-12 2015-02-25 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
US11771775B2 (en) 2012-10-12 2023-10-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10722594B2 (en) 2012-10-12 2020-07-28 Adc Therapeutics S.A. Pyrrolobenzodiazepine-anti-CD22 antibody conjugates
US10646584B2 (en) 2012-10-12 2020-05-12 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US9889207B2 (en) 2012-10-12 2018-02-13 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US11701430B2 (en) 2012-10-12 2023-07-18 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US10994023B2 (en) 2012-10-12 2021-05-04 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US9919056B2 (en) 2012-10-12 2018-03-20 Adc Therapeutics S.A. Pyrrolobenzodiazepine-anti-CD22 antibody conjugates
US11779650B2 (en) 2012-10-12 2023-10-10 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US9931414B2 (en) 2012-10-12 2018-04-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US9931415B2 (en) 2012-10-12 2018-04-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US11690918B2 (en) 2012-10-12 2023-07-04 Medimmune Limited Pyrrolobenzodiazepine-anti-CD22 antibody conjugates
US10780181B2 (en) 2012-10-12 2020-09-22 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10695433B2 (en) 2012-10-12 2020-06-30 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10736903B2 (en) 2012-10-12 2020-08-11 Medimmune Limited Pyrrolobenzodiazepine-anti-PSMA antibody conjugates
US10751346B2 (en) 2012-10-12 2020-08-25 Medimmune Limited Pyrrolobenzodiazepine—anti-PSMA antibody conjugates
US10093736B2 (en) 2012-11-13 2018-10-09 Biontech Ag Agents for treatment of claudin expressing cancer diseases
US9963494B2 (en) 2012-11-28 2018-05-08 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for reducing glucose levels in a subject
US10758590B2 (en) 2012-11-28 2020-09-01 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF 19 polypeptides for treating diabetes
US11066454B2 (en) 2012-11-28 2021-07-20 Ngm Biopharmaceuticals, Inc. Compositions comprising variants and fusions of FGF19 polypeptides
US9895416B2 (en) 2012-12-27 2018-02-20 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having cholestasis
US11103554B2 (en) 2012-12-27 2021-08-31 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants of FGF19 polypeptides for reducing bile acid synthesis in a subject having cirrhosis
US9974833B2 (en) 2012-12-27 2018-05-22 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having pregnancy intrahepatic cholestasis
US9889177B2 (en) 2012-12-27 2018-02-13 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having primary sclerosing cholangitis
US9889178B2 (en) 2012-12-27 2018-02-13 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having nonalcoholic steatohepatitis
US9878009B2 (en) 2012-12-27 2018-01-30 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having error of bile acid synthesis
US9925242B2 (en) 2012-12-27 2018-03-27 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for treatment of nonalcoholic steatohepatitis
US9878008B2 (en) 2012-12-27 2018-01-30 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants and fusions of FGF19 polypeptides for modulating bile acid homeostasis in a subject having bile acid diarrhea or bile acid malabsorption
US11564972B2 (en) 2012-12-27 2023-01-31 Ngm Biopharmaceuticals, Inc. Methods of using compositions comprising variants of FGF19 polypeptides for treating primary biliary cirrhosis in a subject
US10196698B2 (en) 2013-01-23 2019-02-05 The Johns Hopkins University DNA methylation markers for metastatic prostate cancer
US10314890B2 (en) 2013-02-20 2019-06-11 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic cancer
US10946069B2 (en) 2013-02-20 2021-03-16 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic cancer
US9770487B2 (en) 2013-02-20 2017-09-26 Ganymed Pharmaceuticals Ag Combination therapy involving antibodies against claudin 18.2 for treatment of pancreatic adenocarcinoma
US11826402B2 (en) 2013-02-20 2023-11-28 Astellas Pharma Inc. Combination therapy involving antibodies against claudin 18.2 for treatment of metastatic pancreatic adenocarcinoma
WO2014140174A1 (en) 2013-03-13 2014-09-18 Spirogen Sàrl Pyrrolobenzodiazepines and conjugates thereof
WO2014140862A2 (en) 2013-03-13 2014-09-18 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
WO2014159981A2 (en) 2013-03-13 2014-10-02 Spirogen Sarl Pyrrolobenzodiazepines and conjugates thereof
US10472618B2 (en) 2013-03-15 2019-11-12 Atyr Pharma, Inc. Histidyl-tRNA synthetase-Fc conjugates
US10711260B2 (en) 2013-03-15 2020-07-14 Atyr Pharma, Inc. Histidyl-tRNA synthetase-Fc conjugates
US11072787B2 (en) 2013-03-15 2021-07-27 Atyr Pharma Inc. Histidyl-tRNA synthetase-Fc conjugates
US10093915B2 (en) 2013-03-15 2018-10-09 Atyr Pharma Inc. Histidyl-tRNA synthetase-Fc conjugates
US11395852B2 (en) 2013-03-18 2022-07-26 Astellas Pharma Inc. Therapy involving antibodies against Claudin 18.2 for treatment of cancer
US10137195B2 (en) 2013-03-18 2018-11-27 Ganymed Pharmaceuticals Gmbh Therapy involving antibodies against Claudin 18.2 for treatment of cancer
WO2015023355A1 (en) 2013-08-12 2015-02-19 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
US10010624B2 (en) 2013-10-11 2018-07-03 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10029018B2 (en) 2013-10-11 2018-07-24 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US9956299B2 (en) 2013-10-11 2018-05-01 Medimmune Limited Pyrrolobenzodiazepine—antibody conjugates
US9950078B2 (en) 2013-10-11 2018-04-24 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US10369199B2 (en) 2013-10-28 2019-08-06 Ngm Biopharmaceuticals, Inc. Methods of using variants of FGF19 polypeptides for the treatment of cancer
EP2876445A1 (en) * 2013-11-22 2015-05-27 Institut de Cancérologie de l'Ouest Method for in vitro diagnosing and prognosing of triple negative breast cancer recurrence
WO2015075240A3 (en) * 2013-11-22 2015-07-16 Institut De Cancerologie De L'ouest Method for in vitro diagnosing and prognosing of triple negative breast cancer recurrence
US10859577B2 (en) 2013-11-22 2020-12-08 Institut De Cancerologie De L'ouest Method for in vitro diagnosing and prognosing of triple negative breast cancer recurrence
WO2015095223A2 (en) 2013-12-16 2015-06-25 Genentech, Inc. Peptidomimetic compounds and antibody-drug conjugates thereof
WO2015095227A2 (en) 2013-12-16 2015-06-25 Genentech, Inc. Peptidomimetic compounds and antibody-drug conjugates thereof
WO2015095212A1 (en) 2013-12-16 2015-06-25 Genentech, Inc. 1-(chloromethyl)-2,3-dihydro-1h-benzo[e]indole dimer antibody-drug conjugate compounds, and methods of use and treatment
US11596676B2 (en) 2014-01-24 2023-03-07 Ngm Biopharmaceuticals, Inc. Methods of treating nonalcoholic steatohepatitis comprising administering an anti-human beta klotho antibody or binding fragment thereof
US10744191B2 (en) 2014-01-24 2020-08-18 Ngm Biopharmaceuticals, Inc. Beta klotho-binding proteins and methods of use thereof
US10093735B2 (en) 2014-01-24 2018-10-09 Ngm Biopharmaceuticals, Inc. Beta-klotho binding proteins
US10398758B2 (en) 2014-05-28 2019-09-03 Ngm Biopharmaceuticals, Inc. Compositions comprising variants of FGF19 polypeptides and uses thereof for the treatment of hyperglycemic conditions
US11241481B2 (en) 2014-06-16 2022-02-08 Ngm Biopharmaceuticals, Inc. Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
US10456449B2 (en) 2014-06-16 2019-10-29 Ngm Biopharmaceuticals, Inc. Methods and uses for modulating bile acid homeostasis and treatment of bile acid disorders and diseases
WO2016037644A1 (en) 2014-09-10 2016-03-17 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
US10188746B2 (en) 2014-09-10 2019-01-29 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
WO2016040825A1 (en) 2014-09-12 2016-03-17 Genentech, Inc. Anthracycline disulfide intermediates, antibody-drug conjugates and methods
WO2016040856A2 (en) 2014-09-12 2016-03-17 Genentech, Inc. Cysteine engineered antibodies and conjugates
US10420777B2 (en) 2014-09-12 2019-09-24 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof
EP3235820A1 (en) 2014-09-17 2017-10-25 Genentech, Inc. Pyrrolobenzodiazepines and antibody disulfide conjugates thereof
US10517929B2 (en) 2014-10-23 2019-12-31 Ngm Biopharmaceuticals, Inc. Pharmaceutical compositions comprising FGF19 variants
US11141460B2 (en) 2014-11-07 2021-10-12 Ngm Biopharmaceuticals, Inc. Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders
US10434144B2 (en) 2014-11-07 2019-10-08 Ngm Biopharmaceuticals, Inc. Methods for treatment of bile acid-related disorders and prediction of clinical sensitivity to treatment of bile acid-related disorders
US10780096B2 (en) 2014-11-25 2020-09-22 Adc Therapeutics Sa Pyrrolobenzodiazepine-antibody conjugates
WO2016090050A1 (en) 2014-12-03 2016-06-09 Genentech, Inc. Quaternary amine compounds and antibody-drug conjugates thereof
US11702460B2 (en) 2015-03-27 2023-07-18 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against various tumors
US11466072B2 (en) 2015-03-27 2022-10-11 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against various tumors
US11897934B2 (en) 2015-03-27 2024-02-13 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against various tumors
US10501522B2 (en) 2015-03-27 2019-12-10 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against various tumors
US11873329B2 (en) 2015-03-27 2024-01-16 Immatics Biotechnologies Gmbh Peptides and combination of peptides for use in immunotherapy against various tumors
EP3388079A1 (en) * 2015-03-27 2018-10-17 Immatics Biotechnologies GmbH Novel peptides and combination of peptides for use in immunotherapy against various tumors (seq id 253 - rad54b)
US11702473B2 (en) 2015-04-15 2023-07-18 Medimmune Limited Site-specific antibody-drug conjugates
US11059893B2 (en) 2015-04-15 2021-07-13 Bergenbio Asa Humanized anti-AXL antibodies
US10800843B2 (en) 2015-07-29 2020-10-13 Ngm Biopharmaceuticals, Inc. Beta klotho-binding proteins
US11667708B2 (en) 2015-07-29 2023-06-06 Ngm Biopharmaceuticals, Inc. Anti-human beta klotho antibody or binding fragment thereof and methods of their use
WO2017059289A1 (en) 2015-10-02 2017-04-06 Genentech, Inc. Pyrrolobenzodiazepine antibody drug conjugates and methods of use
WO2017064675A1 (en) 2015-10-16 2017-04-20 Genentech, Inc. Hindered disulfide drug conjugates
WO2017068511A1 (en) 2015-10-20 2017-04-27 Genentech, Inc. Calicheamicin-antibody-drug conjugates and methods of use
US10744185B2 (en) 2015-11-09 2020-08-18 Ngm Biopharmaceuticals, Inc. Methods of using variants of FGF19 polypeptides for the treatment of pruritus
US10392393B2 (en) 2016-01-26 2019-08-27 Medimmune Limited Pyrrolobenzodiazepines
US10695439B2 (en) 2016-02-10 2020-06-30 Medimmune Limited Pyrrolobenzodiazepine conjugates
US11517626B2 (en) 2016-02-10 2022-12-06 Medimmune Limited Pyrrolobenzodiazepine antibody conjugates
WO2017165734A1 (en) 2016-03-25 2017-09-28 Genentech, Inc. Multiplexed total antibody and antibody-conjugated drug quantification assay
EP4273551A2 (en) 2016-03-25 2023-11-08 F. Hoffmann-La Roche AG Multiplexed total antibody and antibody-conjugated drug quantification assay
KR102411975B1 (en) 2016-04-06 2022-06-22 이매틱스 바이오테크놀로지스 게엠베하 Peptides and combinations of peptides for use in immunotherapy for AML and other cancers
KR20180132817A (en) * 2016-04-06 2018-12-12 이매틱스 바이오테크놀로지스 게엠베하 Combinations of novel peptides and peptides for use in immunotherapy for AML and other cancers
US10543279B2 (en) 2016-04-29 2020-01-28 Medimmune Limited Pyrrolobenzodiazepine conjugates and their use for the treatment of cancer
WO2017201449A1 (en) 2016-05-20 2017-11-23 Genentech, Inc. Protac antibody conjugates and methods of use
WO2017205741A1 (en) 2016-05-27 2017-11-30 Genentech, Inc. Bioanalytical method for the characterization of site-specific antibody-drug conjugates
WO2017214024A1 (en) 2016-06-06 2017-12-14 Genentech, Inc. Silvestrol antibody-drug conjugates and methods of use
WO2018031662A1 (en) 2016-08-11 2018-02-15 Genentech, Inc. Pyrrolobenzodiazepine prodrugs and antibody conjugates thereof
US11370841B2 (en) 2016-08-26 2022-06-28 Ngm Biopharmaceuticals, Inc. Methods of treating fibroblast growth factor 19-mediated cancers and tumors
WO2018065501A1 (en) 2016-10-05 2018-04-12 F. Hoffmann-La Roche Ag Methods for preparing antibody drug conjugates
US10799595B2 (en) 2016-10-14 2020-10-13 Medimmune Limited Pyrrolobenzodiazepine conjugates
US11612665B2 (en) 2017-02-08 2023-03-28 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US11813335B2 (en) 2017-02-08 2023-11-14 Medimmune Limited Pyrrolobenzodiazepine-antibody conjugates
US11160872B2 (en) 2017-02-08 2021-11-02 Adc Therapeutics Sa Pyrrolobenzodiazepine-antibody conjugates
US11370801B2 (en) 2017-04-18 2022-06-28 Medimmune Limited Pyrrolobenzodiazepine conjugates
US10544223B2 (en) 2017-04-20 2020-01-28 Adc Therapeutics Sa Combination therapy with an anti-axl antibody-drug conjugate
US11767520B2 (en) 2017-04-20 2023-09-26 Atyr Pharma, Inc. Compositions and methods for treating lung inflammation
US11938192B2 (en) 2017-06-14 2024-03-26 Medimmune Limited Dosage regimes for the administration of an anti-CD19 ADC
US11318211B2 (en) 2017-06-14 2022-05-03 Adc Therapeutics Sa Dosage regimes for the administration of an anti-CD19 ADC
US11649250B2 (en) 2017-08-18 2023-05-16 Medimmune Limited Pyrrolobenzodiazepine conjugates
WO2019060398A1 (en) 2017-09-20 2019-03-28 Ph Pharma Co., Ltd. Thailanstatin analogs
US11352324B2 (en) 2018-03-01 2022-06-07 Medimmune Limited Methods
US11524969B2 (en) 2018-04-12 2022-12-13 Medimmune Limited Pyrrolobenzodiazepines and conjugates thereof as antitumour agents
WO2020049286A1 (en) 2018-09-03 2020-03-12 Femtogenix Limited Polycyclic amides as cytotoxic agents
WO2020086858A1 (en) 2018-10-24 2020-04-30 Genentech, Inc. Conjugated chemical inducers of degradation and methods of use
WO2020123275A1 (en) 2018-12-10 2020-06-18 Genentech, Inc. Photocrosslinking peptides for site specific conjugation to fc-containing proteins
WO2020157491A1 (en) 2019-01-29 2020-08-06 Femtogenix Limited G-a crosslinking cytotoxic agents
WO2022023735A1 (en) 2020-07-28 2022-02-03 Femtogenix Limited Cytotoxic agents

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