WO2008021290A2 - Organ-specific proteins and methods of their use - Google Patents

Organ-specific proteins and methods of their use Download PDF

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Publication number
WO2008021290A2
WO2008021290A2 PCT/US2007/017868 US2007017868W WO2008021290A2 WO 2008021290 A2 WO2008021290 A2 WO 2008021290A2 US 2007017868 W US2007017868 W US 2007017868W WO 2008021290 A2 WO2008021290 A2 WO 2008021290A2
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Prior art keywords
organ
specific proteins
specific
disease
detection reagents
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English (en)
French (fr)
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WO2008021290A3 (en
WO2008021290A9 (en
WO2008021290A8 (en
Inventor
Leroy Hood
Patricia M. Beckmann
Richard Johnson
Marcello Marelli
Xiaojun Li
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Institute for Systems Biology
Homestead Clinical Corp
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Institute for Systems Biology
Homestead Clinical Corp
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Priority to AU2007284651A priority Critical patent/AU2007284651B2/en
Priority to CA002660286A priority patent/CA2660286A1/en
Priority to EP07836742A priority patent/EP2057465A4/en
Priority to JP2009523868A priority patent/JP5244103B2/ja
Priority to US12/376,951 priority patent/US8586006B2/en
Application filed by Institute for Systems Biology, Homestead Clinical Corp filed Critical Institute for Systems Biology
Publication of WO2008021290A2 publication Critical patent/WO2008021290A2/en
Publication of WO2008021290A8 publication Critical patent/WO2008021290A8/en
Publication of WO2008021290A3 publication Critical patent/WO2008021290A3/en
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Priority to US14/072,651 priority patent/US20140106981A1/en
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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • G01N33/6803—General methods of protein analysis not limited to specific proteins or families of proteins
    • G01N33/6845—Methods of identifying protein-protein interactions in protein mixtures
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/68—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving proteins, peptides or amino acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2800/00—Detection or diagnosis of diseases
    • G01N2800/52—Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis

Definitions

  • CD-ROM No. 1 is labeled "COPY 1 - SEQUENCE LISTING PART”
  • CD-ROM No.2 is labeled "COPY 2 - SEQUENCE LISTING PART”
  • CD-ROM No. 2 contains the file 405pc.app.txt which is 132 MB and created on 9 August 2007
  • CD-ROM no. 1 is labeled "COPY 1 -TABLES PART”
  • CD-ROM no.2 is labeled "COPY 2 -TABLES PART”
  • CD-ROM no. 3 is labeled "COPY 3 - TABLES PART”
  • the present invention relates generally to organ-specific proteins and polynucleotides that encode them.
  • the invention relates to diagnostic and prognostic panels, sets, and individual agents comprising reagents or probes to detect organ-specific proteins or polynucleotides and methods of identifying and using organ-specific proteins.
  • the ability to monitor normal health and to detect the onset of disease at a very early and treatable stage is critical to diagnostic medicine. Early detection for most diseases, including diseases of the lung, cardiovascular disease, cancer, hematological disease (including most hematological cancers), inflammatory disorders, metabolic disease and neurological disease may permit treatment at an earlier stage that will produce healthier and typically more successful outcomes for the patient. Accordingly, there is a great need for more sensitive and accurate assays and methods to measure health and detect disease and monitor treatment at earlier stages.
  • Diagnostic assays are often incapable of identifying truly informative proteins for analyses and, to be useful, often require significant changes in protein composition in for example, blood, at the cellular level to detect the presence of disease or to define a change in health from normal.
  • Current diagnostic assays may not detect disease until it has progressed to a stage where it is too late for effective treatment. For example, most cancers may be cured if diagnosed at the earliest stage. If cancer is diagnosed at later or advanced stages, effective treatment may be difficult or impossible and lead to reduced patient survival. In general, current diagnostic assays have severe limitations that prevent early detection and diagnosis.
  • proteins are not disease-specific in that multiple organs synthesize them and different diseases may perturb their expression in different ways.
  • the specific proteins that are released in the disease state that are markers of the disease may be difficult to identify or to measure because of the enormous dynamic range of protein expression in the blood and because of the enormous protein complexity in the blood.
  • These proteins must be distinguished from other protein markers found in the blood that are not likely to be disease markers.
  • Other protein markers that are present in the blood that are not typically considered indicators of disease include proteins released due to: cellular damage, normal cellular turnover, stress responses (liver proteins) or other slight protein changes in the plasma. Additionally, 22 proteins constitute about 99% of the total blood protein mass.
  • albumin comprises about 51 % of this total blood protein mass. Most of these abundant blood proteins are not useful diagnostic markers. Useful diagnostic proteins are present in much lower abundance and typically in 1 % of the remaining proteins (Lee et a/., Curr Opin in Chem Bio (2006) 10:1-8). Many proteins are released into the blood following physiological changes from normal to the disease state and are likely present in plasma as low abundance proteins. Furthermore, blood proteins exhibit large differences in the concentration of the most abundant and least abundant proteins that range over many orders of magnitude. Proteins are expressed in blood across a range of about 10 10 between the numbers of proteins.
  • a diagnostic panel comprising a plurality of detection reagents wherein each detection reagent is specific for one organ-specific protein; wherein the organ- specific proteins detected by the plurality of detection reagents are selected from any one of the organ-specific protein sets provided in the Tables herein; and wherein the plurality of detection reagents is selected such that the level of at least one of the organ-specific proteins detected by the plurality of detection reagents in a blood sample from a subject afflicted with a disease affecting the organ from which the organ-specific proteins are derived is above or below a predetermined normal range.
  • a diagnostic panel comprising a plurality of detection reagents wherein each detection reagent is specific for one organ-specific protein; wherein the organ- specific proteins detected by the plurality of detection reagents are selected from two or more of the organ-specific protein sets provided in the Tables herein; and wherein the plurality of detection reagents is selected such that the level of at least one of the organ-specific proteins detected by the plurality of detection reagents in a blood sample from a subject afflicted with a disease affecting the organs from which the organ-specific proteins are derived is above or below a predetermined normal range.
  • a method for defining a biological state of a subject comprising (a) measuring the level of at least two organ-specific proteins selected from any one of the organ-specific protein sets provided in the Tables herein in a blood sample from the subject; and (b) comparing the level determined in (a) to a predetermined normal level of the at least two organ-specific proteins; wherein a level of at least one of the two organ-specific proteins that is above or below the predetermined normal level defines the biological state of the subject.
  • the level of the at least two organ-specific proteins is measured using an immunoassay, e.g., by an ELISA assay.
  • the level of the at least two organ-specific proteins is measured using mass spectrometry, an aptamer capture assay or any other suitable technique.
  • a method for defining a biological state of a subject comprising (a) measuring the level of at least two organ-specific proteins selected from any two or more of the organ-specific protein sets provided in the Tables herein in a blood sample from the subject; and (b) comparing the level determined in (a) to a predetermined normal level of the at least two organ-specific proteins; wherein a level of at least one of the two organ-specific proteins that is above or below the predetermined normal level defines the biological state of the subject.
  • the level of the at least two organ-specific proteins is measured using an immunoassay, e.g., by an ELISA assay.
  • the level of the at least two organ-specific proteins is measured using mass spectrometry, an aptamer capture assay or any other suitable technique.
  • a method for defining a disease-associated organ-specific blood fingerprint comprising; (a) measuring the level of at least two organ-specific proteins selected from any one of the organ-specific protein sets provided in the Tables herein in a blood sample from a subject determined to have a disease affecting the organ from which the at least two organ-specific proteins are selected; and (b) comparing the level of the at least two organ-specific proteins determined in (a) to a predetermined normal level of the at least two organ-specific proteins; wherein a level of at least one of the at least two organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defines the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of at least three organ-specific proteins selected from any one of the organ-specific protein sets provided in the Tables herein and wherein a level of at least two of the at least three organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defines the disease- associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of four or more organ-specific proteins selected from any one of the organ-specific protein sets provided in the Tables herein and wherein a level of at least three of the four or more organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defines the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of four or more organ-specific proteins selected from any one of the organ-specific protein sets provided in the Tables herein and wherein a level of at least four of the four or more organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defines the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of five or more organ-specific proteins selected from any one of the organ-specific protein sets provided in the Tables herein and wherein a level of at least five of the five or more organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defines the disease-associated organ-specific blood fingerprint.
  • Another aspect of the invention relates to a method for defining a disease-associated organ-specific blood fingerprint comprising; (a) measuringthe level of at least two organ-specific proteins selected from two or more of the organ-specific protein sets provided in the Tables herein in a blood sample from a subject determined to have a disease of interest; and (b) comparing the level of the at least two organ-specific proteins determined in (a) to a predetermined normal level of the at least two organ-specific proteins; wherein a level of at least one of the at least two organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defining the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of at least three organ-specific proteins selected from two or more of the organ-specific protein sets provided in the Tables herein and wherein a level of at least two of the at least three organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defining the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of four or more organ-specific proteins selected from two or more of the organ-specific protein sets provided in the Tables herein and wherein a level of at least three of the four or more organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defining the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of four or more organ-specific proteins selected from two or more of the organ- specific protein sets provided in the Tables herein and wherein a level of at least four of the four or more organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defining the disease-associated organ-specific blood fingerprint.
  • step (a) comprises measuring the level of five or more organ-specific proteins selected from two or more of the organ-specific protein sets provided in the Tables herein and wherein a level of at least five of the five or more organ-specific proteins in the blood sample from the subject determined to have the disease that is below or above the corresponding predetermined normal level defining the disease-associated organ-specific blood fingerprint.
  • a method for detecting perturbation of a normal biological state in a subject comprising, (a) contacting a blood sample from the subject with a plurality of detection reagents wherein each detection reagent is specific for one organ- specific protein; wherein the organ-specific proteins detected by the plurality of detection reagents are selected from any one of the organ-specific protein sets provided in the Tables herein; (b) measuring the amount of the organ-specific protein detected in the blood sample by each detection reagent; and (c) comparing the amount of the organ-specific protein detected in the blood sample by each detection reagent to a predetermined normal amount for each respective organ- specific protein; wherein a statistically significant altered level in one or more of the organ-specific proteins indicates a perturbation in the normal biological state.
  • the invention provides a method for detecting perturbation of a normal biological state in a subject comprising, (a) contacting a blood sample from the subject with a plurality of detection reagents wherein each detection reagent is specific for one organ-specific protein; wherein the organ- specific proteins detected by the plurality of detection reagents are selected from two or more of the organ-specific protein sets provided in the Tables herein; (b) measuring the amount of the organ-specific protein detected in the blood sample by each detection reagent; and (c) comparing the amount of the organ-specific protein detected in the blood sample by each detection reagent to a predetermined normal amount for each respective organ-specific protein; wherein a statistically significant altered level in one or more of the organ-specific proteins indicates a perturbation in the normal biological state.
  • Another aspect of the invention provides a method for detecting prostate disease in a subject comprising, (a) contacting a blood sample from the subject with a plurality of detection reagents wherein each detection reagent is specific for one prostate-specific protein; wherein the prostate-specific proteins are selected from the organ-specific protein set provided in Table 21 ; (b) measuring the amount of the organ-specific protein detected in the blood sample by each detection reagent; and (c) comparing the amount of the organ-specific protein detected in the blood sample by each detection reagent to a predetermined normal control amount for each respective organ-specific protein; wherein a statistically significant altered level in one or more of the organ-specific proteins indicates a perturbation in the normal biological state.
  • the prostate- specific proteins are selected from those proteins in Table 21 designated as secreted and with a specificity of 0.9 or greater.
  • the prostate disease is selected from the group consisting of prostate cancer, prostatitis, and benign prostatic hyperplasia.
  • the plurality of detection reagents comprises at least 2, at least 3, at least 4, at least 5 or at least 6 detection reagents as described herein.
  • a method for monitoring a response to a therapy in a subject comprising the steps of: (a) measuring in a blood sample obtained from the subject the level of a plurality of organ-specific proteins, wherein the plurality of organ-specific proteins are selected from any one of the organ-specific protein sets provided in the Tables herein; (b) repeating step (a) using a blood sample obtained from the subject after undergoing therapy; and (c) comparing the level of the plurality of organ-specific proteins detected in step (b) to the amount detected in step (a) and therefrom monitoring the response to the therapy in the patient.
  • a method for monitoring a response to a therapy in a subject comprising the steps of: (a) measuring in a blood sample obtained from the subject the level of a plurality of organ-specific proteins, wherein the plurality of organ-specific proteins are selected from two or more of the organ-specific protein sets provided in the Tables herein; (b) repeating step (a) using a blood sample obtained from the subject after undergoing therapy; and (c) comparing the level of the plurality of organ-specific proteins detected in step (b) to the amount detected in step (a) and therefrom monitoring the response to the therapy in the patient.
  • the plurality of detection reagents may be of any suitable or desire number, and will generally be between about two and 100 detection reagents. In one embodiment, the plurality of detection reagents is selected such that the level of at least two, at least three or at least four of the organ-specific proteins detected by the plurality of detection reagents in a blood sample from a subject afflicted with a disease affecting the organ from which the organ-specific proteins are derived is above or below a predetermined normal range.
  • the organ-specific proteins detected by the plurality of detection reagents may be selected from any one of the organ-specific protein sets provided in the Tables herein, and from among the proteins identified as secreted. In one embodiment, the organ-specific proteins detected by the plurality of detection reagents are selected from any one of the organ-specific protein sets provided in the Tables herein and from among the proteins identified as transmembrane. In another related embodiment, the organ-specific proteins detected by the plurality of detection reagents are selected from any one of the organ-specific protein sets provided in the Tables herein and from among the proteins with a specificity of 0.8 or greater.
  • the organ-specific proteins detected by the plurality of detection reagents are selected from any one of the organ-specific protein sets provided in Tables 47-79 and from among the proteins identified by MPSS data and SBS data. In this regard, these proteins are identified in Tables 47-79 by an "&".
  • the detection reagent used in the methods of the invention can be any suitable reagent for detection of the protein or proteins of interest.
  • the detection reagent comprises an antibody (e.g., monoclonal antibody) or an antigen-binding fragment thereof.
  • the detection reagent comprises a DNA or RNA aptamer.
  • the detection reagent comprises an isotope labeled peptide.
  • the disease or diseases evaluated using the methods described herein can include essentially any diseases for which the organ-specific protein sets of the invention provide information of diagnostic or other medical value.
  • the disease affects the adrenal gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 1.
  • the disease affects the bladder and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 2.
  • the disease is bladder cancer and the at least two organ-specific proteins are selected from Table 2.
  • the disease affects the bone marrow and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 3.
  • the disease affects the brain amygdala and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 4. In another embodiment, the disease affects the colon and the organ- specific proteins detected by the plurality of detection reagents are selected from Table 11. In another embodiment, the colon disease is colon cancer and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 11. In another embodiment, the disease affects the heart and the organ- specific proteins detected by the plurality of detection reagents are selected from Table 12.
  • the disease affects the kidney and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 13.
  • the disease is kidney cancer and the at least two organ-specific proteins are selected from Table 13.
  • the disease affects the lung and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 14.
  • the disease affects the mammary gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 15. In another embodiment, the disease is breast cancer and the at least two organ-specific proteins are selected from Table 15. In another embodiment, the disease affects the peripheral blood and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 16.
  • the disease affects the pancreas and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 17.
  • the disease affects the peripheral blood and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 18.
  • the disease affects the pituitary gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 19.
  • the disease affects the prostate and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 21. In another embodiment, the disease is prostate cancer and the at least two organ-specific proteins are selected from Table 21. In another embodiment, the disease affects the retina and the organ- specific proteins detected by the plurality of detection reagents are selected from Table 22.
  • the disease affects the salivary gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 23.
  • the disease affects the Small intestine and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 24. In another embodiment, the disease affects the Spinal cord and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 25.
  • the disease affects the spleen and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 26.
  • the disease affects the stomach and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 27.
  • the disease affects the testis and the organ- specific proteins detected by the plurality of detection reagents are selected from Table 28.
  • the disease affects the thymus and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 29. In another embodiment, the disease affects the thyroid and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 30.
  • the disease affects the uterus and the organ- specific proteins detected by the plurality of detection reagents are selected from Table 32. In another embodiment, the disease is Cushing's syndrome.
  • the disease is a bladder disease and the organ-specific proteins detected by the plurality of detection reagents are selected from any one or both of Tables 13 and 2.
  • the disease is a neurological disease and the organ-specific proteins detected by the plurality of detection reagents are selected from any one or more of Tables 3, 4, 5, 6, 7, 8 and 9.
  • Figure 1 is a schematic of the instant invention and provides a general overview of the steps involved in one embodiment of the invention.
  • Figure 2 is a photograph of a Western blot of serum from normal patients, early stage prostate cancer patients and late stage prostate cancer patients identifying differential expression of prostate-specific proteins.
  • Serum samples from normal (1 ,2,8,13), and from early (3-7) and late (9-12) prostate cancer patients were resolved by SDS-PAGE and visualized by western blotting using antibodies directed against STEAP2 and TGM4. The experiment was conducted as described in Example 4.
  • SEQ ID NOs: 1-368 correspond to polynucleotides encoding adrenal gland-specific proteins as described in Table 1.
  • SEQ ID Nos: 369-736 are the amino acid sequences of adrenal gland-specific proteins as described in Table 1.
  • SEQ ID NOs: 737-1028 are the polynucleotide sequences of the MPSS signature sequences of adrenal gland-specific proteins as described in Table 1.
  • SEQ ID NOs: 1029-1311 correspond to polynucleotides encoding bladder-specific proteins as described in Table 2.
  • SEQ ID NOs: 1312-1594 are the amino acid sequences of bladder- specific proteins as described in Table 2.
  • SEQ ID Nos: 1595-1795 are the polynucleotide sequences of the MPSS signature sequences of bladder-specific proteins as described in Table 2.
  • SEQ ID Nos: 1796-2094 correspond to polynucleotides encoding bone marrow-specific proteins as described in Table 3.
  • SEQ ID NOs: 2095-2393 are the amino acid sequences of bone marrow-specific proteins as described in Table 3.
  • SEQ ID NOs: 2394-2623 are the polynucleotide sequences of the MPSS signature sequences of bone marrow-specific proteins as described in Table 3.
  • SEQ ID NOs: 2624-2979 correspond to polynucleotides encoding brain amygdala-specific proteins as described in Table 4.
  • SEQ ID Nos: 2980-3335 are the amino acid sequences of brain amygdala-specific proteins as described in Table 4.
  • SEQ ID NOs: 3336-3579 are the polynucleotide sequences of the MPSS signature sequences of brain amygdala-specific proteins as described in Table 4.
  • SEQ ID NOs: 3580-4128 correspond to polynucleotides encoding brain caudate nucleus-specific proteins as described in Table 5.
  • SEQ ID Nos: 4129-4677 are the amino acid sequences of brain caudate nucleus-specific proteins as described in Table 5.
  • SEQ ID Nos: 4678-5069 are the polynucleotide sequences of the MPSS signature sequences of brain caudate nucleus-specific proteins as described in Table 5.
  • SEQ ID NOs: 5070-5903 correspond to polynucleotides encoding brain cerrebellum-specific proteins as described in Table 6.
  • SEQ ID Nos: 5904-6737 are the amino acid sequences of brain cerrebellum-specific proteins as described in Table 6.
  • SEQ ID Nos: 6738-7211 are the polynucleotide sequences of the MPSS signature sequences of brain cerrebellum-specific proteins as described in Table 6.
  • SEQ ID NOs: 7212-7541 correspond to polynucleotides encoding brain corpus callosum-specific proteins as described in Table 7.
  • SEQ ID Nos: 7542-7871 are the amino acid sequences of brain corpus callosum-specific proteins as described in Table 7.
  • SEQ ID NOs: 7872-8113 are the polynucleotide sequences of the MPSS signature sequences of brain corpus callosum-specific proteins as described in Table 7.
  • SEQ ID NOs: 8114-9441 correspond to polynucleotides encoding brain fetal-specific proteins as described in Table 8.
  • SEQ ID NOs: 9442-10769 are the amino acid sequences of brain fetal-specific proteins as described in Table 8.
  • SEQ ID NOs: 10770-11903 are the polynucleotide sequences of the
  • SEQ ID NOs: 11904-12159 correspond to polynucleotides encoding brain hypothalamus-specific proteins as described in Table 9.
  • SEQ ID Nos: 12160-12415 are the amino acid sequences of brain hypothalamus-specific proteins as described in Table 9.
  • SEQ ID NOs: 12416-12669 are the polynucleotide sequences of the MPSS signature sequences of brain hypothalamus-specific proteins as described in Table 9.
  • SEQ ID NOs: 12670-12877 correspond to polynucleotides encoding brain thalamus-specific proteins as described in Table 10.
  • SEQ ID NOs: 12878-13085 are the amino acid sequences of brain thalamus-specific proteins as described in Table 10.
  • SEQ ID NOs: 13086-13264 are the polynucleotide sequences of the MPSS signature sequences of brain thalamus-specific proteins as described in Table 10.
  • SEQ ID NOs: 13265-13531 correspond to polynucleotides encoding colon-specific proteins as described in Table 11.
  • SEQ ID NOs: 13532-13798 are the amino acid sequences of colon- specific proteins as described in Table 11.
  • SEQ ID Nos: 13799-14035 are the polynucleotide sequences of the
  • SEQ ID NOs: 14036-14449 correspond to polynucleotides encoding heart-specific proteins as described in Table 12.
  • SEQ ID Nos: 14450-14863 are the amino acid sequences of heart-specific proteins as described in Table 12.
  • SEQ ID NOs: 14864-15374 are the polynucleotide sequences of the MPSS signature sequences of heart-specific proteins as described in Table 12.
  • SEQ ID NOs: 15375-15550 correspond to polynucleotides encoding kidney-specific proteins as described in Table 13.
  • SEQ ID NOs: 15551-15726 are the amino acid sequences of kidney- specific proteins as described in Table 13.
  • SEQ ID NOs: 15727-15904 are the polynucleotide sequences of the MPSS signature sequences of kidney-specific proteins as described in Table 13.
  • SEQ ID NOs: 15905-16301 correspond to polynucleotides encoding lung-specific proteins as described in Table 14.
  • SEQ ID Nos: 16302-16698 are the amino acid sequences of lung-specific proteins as described in Table 14.
  • SEQ ID Nos: 16669-17022 are the polynucleotide sequences of the MPSS signature sequences of lung-specific proteins as described in Table 14.
  • SEQ ID Nos: 17023-17182 correspond to polynucleotides encoding mammary gland-specific proteins as described in Table 15.
  • SEQ ID Nos: 17183-17342 are the amino acid sequences of mammary gland-specific proteins as described in Table 15.
  • SEQ ID Nos: 17343-17493 are the polynucleotide sequences of the MPSS signature sequences of mammary gland-specific proteins as described in Table 15.
  • SEQ ID NOs: 17494-17962 correspond to polynucleotides encoding monocyte-specific proteins as described in Table 16.
  • SEQ ID NOs: 17963-18431 are the amino acid sequences of monocyte-specific proteins as described in Table 16.
  • SEQ ID Nos: 18432-18843 are the polynucleotide sequences of the MPSS signature sequences of monocyte-specific proteins as described in Table 16.
  • SEQ ID NOs: 18844-18872 correspond to polynucleotides encoding pancreas-specific proteins as described in Table 17.
  • SEQ ID Nos: 18873-18901 are the amino acid sequences of pancreas-specific proteins as described in Table 17.
  • SEQ ID Nos: 18902-18946 are the polynucleotide sequences of the
  • SEQ ID Nos: 18947-19350 correspond to polynucleotides encoding peripheral blood lymphocyte-specific proteins as described in Table 18.
  • SEQ ID Nos: 19351-19754 are the amino acid sequences of peripheral blood lymphocyte-specific proteins as described in Table 18.
  • SEQ ID Nos: 19755-20134 are the polynucleotide sequences of the MPSS signature sequences of peripheral blood lymphocyte-specific proteins as described in Table 18.
  • SEQ ID Nos: 20135-20275 correspond to polynucleotides encoding pituitary gland-specific proteins as described in Table 19.
  • SEQ ID Nos: 20276-20416 are the amino acid sequences of pituitary gland-specific proteins as described in Table 19.
  • SEQ ID Nos: 20417-20575 are the polynucleotide sequences of the MPSS signature sequences of pituitary gland-specific proteins as described in Table 19.
  • SEQ ID NOs: 20576-20842 correspond to polynucleotides encoding placenta-specific proteins as described in Table 20.
  • SEQ ID NOs: 20843-21109 are the amino acid sequences of placenta-specific proteins as described in Table 20.
  • SEQ ID NOs: 21110-21435 are the polynucleotide sequences of the MPSS signature sequences of placenta-specific proteins as described in Table 20.
  • SEQ ID NOs: 21436-22022 correspond to polynucleotides encoding prostate-specific proteins as described in Table 21.
  • SEQ ID Nos: 22023-22609 are the amino acid sequences of prostate-specific proteins as described in Table 21.
  • SEQ ID Nos: 22610-23274 are the polynucleotide sequences of the MPSS signature sequences of prostate-specific proteins as described in Table 21.
  • SEQ ID NOs: 23275-23605 correspond to polynucleotides encoding retina-specific proteins as described in Table 22.
  • SEQ ID Nos: 23606-23936 are the amino acid sequences of retina-specific proteins as described in Table 22.
  • SEQ ID Nos: 23937-24304 are the polynucleotide sequences of the
  • SEQ ID NOs: 24305-24434 correspond to polynucleotides encoding salivary gland-specific proteins as described in Table 23.
  • SEQ ID Nos: 24435-24564 are the amino acid sequences of salivary gland-specific proteins as described in Table 23.
  • SEQ ID Nos: 24565-24713 are the polynucleotide sequences of the MPSS signature sequences of salivary gland-specific proteins as described in Table 23.
  • SEQ ID NOs: 24714-24916 correspond to polynucleotides encoding small intestine-specific proteins as described in Table 24.
  • SEQ ID NOs: 24917-2519 are the amino acid sequences of small intestine-specific proteins as described in Table 24.
  • SEQ ID NOs: 25120-25337 are the polynucleotide sequences of the MPSS signature sequences of small intestine-specific proteins as described in Table 24.
  • SEQ ID NOs: 25338-25477 correspond to polynucleotides encoding spinal cord-specific proteins as described in Table 25.
  • SEQ ID Nos: 25478-25617 are the amino acid sequences of spinal cord-specific proteins as described in Table 25.
  • SEQ ID Nos: 25618-25808 are the polynucleotide sequences of the
  • SEQ ID NOs: 25809-26278 correspond to polynucleotides encoding spleen-specific proteins as described in Table 26.
  • SEQ ID NOs: 26279-26748 are the amino acid sequences of spleen- specific proteins as described in Table 26.
  • SEQ ID NOs: 26749-27329 are the polynucleotide sequences of the MPSS signature sequences of spleen-specific proteins as described in Table 26.
  • SEQ ID NOs: 27330-27359 correspond to polynucleotides encoding stomach-specific proteins as described in Table 27.
  • SEQ ID Nos: 27360-27389 are the amino acid sequences of stomach-specific proteins as described in Table 27.
  • SEQ ID Nos: 27390-27422 are the polynucleotide sequences of the MPSS signature sequences of stomach-specific proteins as described in Table 27.
  • SEQ ID Nos: 27423-28424 correspond to polynucleotides encoding testis-specific proteins as described in Table 28.
  • SEQ ID Nos: 28425-29426 are the amino acid sequences of testis-specific proteins as described in Table 28.
  • SEQ ID NOs: 29427-30466 are the polynucleotide sequences of the MPSS signature sequences of testis-specific proteins as described in Table 28.
  • SEQ ID NOs: 30467-30729 correspond to polynucleotides encoding thymus-specific proteins as described in Table 29.
  • SEQ ID Nos: 30730-30992 are the amino acid sequences of thymus- specific proteins as described in Table 29.
  • SEQ ID Nos: 30993-31348 are the polynucleotide sequences of the
  • SEQ ID NOs: 31349-31510 correspond to polynucleotides encoding thyroid-specific proteins as described in Table 30.
  • SEQ ID Nos: 31511-31672 are the amino acid sequences of thyroid-specific proteins as described in Table 30.
  • SEQ ID NOs: 31673-31846 are the polynucleotide sequences of the MPSS signature sequences of thyroid-specific proteins as described in Table 30.
  • SEQ ID NOs: 31847-31888 correspond to polynucleotides encoding trachea-specific proteins as described in Table 31.
  • SEQ ID NOs: 31889-31930 are the amino acid sequences of trachea-specific proteins as described in Table 31.
  • SEQ ID NOs: 31931-32002 are the polynucleotide sequences of the MPSS signature sequences of trachea-specific proteins as described in Table 31.
  • SEQ ID NOs: 32003-32065 correspond to polynucleotides encoding uterus-specific proteins as described in Table 32.
  • SEQ ID NOs: 32066-32128 are the amino acid sequences of uterus- specific proteins as described in Table 32.
  • SEQ ID Nos: 32129-32206 are the polynucleotide sequences of the
  • MPSS signature sequences of uterus-specific proteins as described in Table 32 SEQ ID NOs: 25362; 5142; 8639; 15453; 15915; 23547; 23548; and
  • 17925 correspond to polynucleotides encoding organ-specific glycosylated proteins identified from a sample of normal human serum as described in Table 34.
  • SEQ ID NOs: 25502; 5976; 9967; 15629; 16312; 23878; 23879; and 18394 are the amino acid sequences of organ-specific glycosylated proteins identified from a sample of normal human serum as described in Table 34.
  • the following SEQ ID NOs correspond to the polynucleotides encoding specifictomaleorgan— prostate-specific proteinsas described inTable
  • 36A identified using MPSS: 21436; 21437; 15907; 21438; 21439; 21440; 21441;
  • Thefollowing SEQ ID NOs correspond to the amino acid sequences of specific to male organ - prostate-specific proteins as described in Table 36A identified using MPSS: 22023; 22024; 16304; 22025; 22026; 22027; 22028; 4131;
  • 22301 22302; 22303; 32225; 22304; 22305; 22306; 22307; 22308; 22309; 22310; 22311; 22312; 22313; 22314; 22315; 22316; 22317; 22318; 22319; 22320; 22321;
  • SEQ ID NOs correspond to the polynucleotides encoding specific to male organ — Testis-specific proteins as described in Table 37A identified using MPSS: 27423; 27424; 14038; 27425; 27426; 21443; 27427;
  • Thefollowing SEQ ID NOs correspondtotheaminoacid sequences of specific to male organ — testis-specific proteins as described in Table 37A identified using MPSS: 28425; 28426; 14452; 28427; 28428; 22030; 28429;
  • 29240 6567; 29241; 29242; 29243; 29244; 29245; 651; 13035; 652; 29246;
  • 29400 29401; 10724; 10725; 6714; 29402; 29403; 729; 29404; 12411; 4661; 29405; 4669; 1590; 26737; 13796; 29406; 13082; 29407; 29408; 29409; 26743; 26744; 29410; 29411; 29412; 29413; 29414; 29415; 29416; 29417; 29418; 29419;
  • SEQ ID NOs correspond to the polynucleotides encoding specific to Female Organ - Mammary Gland-specific proteins as described in Table 38A identified using MPSS: 17023; 17024; 17025; 17026;
  • SEQ ID NOs correspond to the amino acid sequences of specific to Female Organ - Mammary Gland-specific proteins as described in Table 38A identified using MPSS: 17183; 17184; 17185; 17186; 32329; 9483;
  • SEQ ID NOs correspond to the polynucleotides encoding specific to Female Organ — Uterus-specific proteins as described in
  • SEQ ID NOs correspond to the polynucleotides encoding CL1 prostate cancer cell-specific proteins as described in Table 4OA identified using MPSS: 32374; 17023; 32375; 32376; 12; 13; 32377; 32378; 5110;
  • SEQ ID NOs correspond to the amino acid sequences of CL1 prostate cancer cell-specific proteins as described in Table 4OA identified using MPSS: 32481; 17183; 32482; 32483; 380; 381; 32484; 32485; 5944; 5945;
  • SEQ ID NOs correspond to the polynucleotides encoding LNCaP prostate cancer cell-specific proteins as described in Table 41A identified using MPSS: 32757; 32758; 32759; 32760; 21467; 32761; 32762;
  • Thefollowing SEQ ID NOs correspond tothe amino acid sequences of LNCaP prostate cancercell-specificproteins asdescribed inTable41Aidentified using MPSS: 32813; 32814; 32815; 32816; 22054; 32817; 32818; 32819; 32820; 23627; 23628; 23629; 32821; 30745; 32822; 32823; 426; 427; 428; 6030; 32824;
  • SEQ ID NOs correspond to the polynucleotides encoding male organ, prostate-specific proteins identified using MPSS as described in Table 42A and Example 7: 21436; 21437; 15907; 21438; 21439;
  • Thefollowing SEQ ID NOs correspondtotheamino acid sequences of male organ, prostate-specific proteins identified using MPSS as described in Table 42A and Example 7: 22023; 22024; 16304; 22025; 22026; 22027; 22028;
  • SEQ ID NOs correspond tothe amino acid sequences of adrenal gland-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 370; 371 ; 373; 374;
  • Thefollowing SEQ ID NOs correspond tothe amino acid sequences ofbladder-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 1313; 1316; 1317; 1318; 1319;
  • SEQ ID NOs correspond tothe amino acid sequences of bone marrow-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 2095; 2096; 2097;
  • SEQ ID NOs correspond to the amino acid sequences of brain amygdala-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 2980; 2098; 2099;
  • SEQ ID NOs correspond tothe amino acid sequences of Brain Caudate Nucleus-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 4135; 4138;
  • Thefollowing SEQ IDNOs correspond tothe amino acid sequences of Brain Cerebellum-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 5904; 2095; 2096;
  • Thefollowing SEQ ID NOs correspond to theamino acid sequences of Brain Corpus Callosum-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 7543; 7544; 7545; 7547; 7548; 7552; 7553; 2989; 7558; 2113; 7560; 7561 ; 7562; 7563; 7568;
  • Thefollowing SEQ ID NOs correspond tothe amino acid sequences ofBrain Hypothalamus-specific proteins identified using MPSS and thathave been identified by mass spectrometry as described inTable43A: 2980; 12162; 373; 374;
  • Thefollowing SEQ ID NOs correspond to the amino acid sequences of Brain Thalamus-specific proteins identified using MPSS and that have been identified by mass spectrometryas described in Table 43A: 12878; 12879; 12880; 12890; 4177; 12891; 12893; 12895; 12896; 12897; 12898; 12902; 12903; 12904;
  • SEQ ID NOs correspond to the amino acid sequences of Colon-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 13533; 13534; 13535; 13536;
  • Thefollowing SEQ ID NOs correspond totheamino acid sequences of heart-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table43A: 5904; 14450; 14453; 1313; 14454;
  • Thefollowing SEQ ID NOs correspond totheamino acid sequences ofkidney-specific proteins identified using MPSS and that have been identified by mass spectrometry as described inTable43A: 15552; 1319; 15561; 15562; 15563;
  • Thefollowing SEQ ID NOs correspond to the amino acid sequences of lung-specific proteins identified using MPSS and that have been identified by mass spectrometry as described inTable 43A: 16302; 16303; 16304; 5911; 5912;
  • SEQ ID NOs correspond totheamino acid sequences of mammary gland-specific proteins identified using MPSS and that have been identified bymassspectrometryasdescribed inTable43A: 17184; 17185; 17186;
  • SEQ ID NOs correspond tothe amino acid sequences ofpancreas-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 18873; 18874; 18875; 18876;
  • Thefollowing SEQ ID NOs correspondtothe amino acid sequences of PBL-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 19351; 16302; 19353; 14455;
  • SEQ ID NOs correspond to the amino acid sequences of pituitary gland-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 5906; 5907; 5908; 5909; 5910; 5911 ; 5912; 20276; 20280; 20281; 20282; 20283; 7561; 7562; 20293;
  • Thefollowing SEQ ID NOs correspond to the amino acid sequences of placenta-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 20843; 375; 20844; 1318; 20849; 20850; 20851; 5925; 20852; 2112; 1330; 20858; 20859; 20860; 20861;
  • SEQ ID NOs correspond tothe amino acid sequences of prostate-specific proteins identified using MPSS and that have been identified by mass spectrometry as described in Table 43A: 16304; 22026; 22027; 13537;

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