Organ-Specific Proteins and Methods of Their Use

Abstract

The present invention relates generally to methods for identifying and using organ-specific proteins and transcripts. The present invention further provides compositions comprising organ-specific proteins and transcripts encoding the same, detection reagents for detecting such proteins and transcripts, and diagnostic panels, kits and arrays for measuring organ-specific proteins/transcripts in blood, biological tissue or other biological fluid.

What is claimed is: 
     
         1 . 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 Tables 1-32, 36-45 and 47-79; 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.   
     
     
         2 . The diagnostic panel of  claim 1  wherein the plurality of detection reagents is selected such that the level of at least two 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. 
     
     
         3 . The diagnostic panel of  claim 1  wherein the plurality of detection reagents is selected such that the level of at least three 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. 
     
     
         4 . The diagnostic panel of  claim 1  wherein the plurality of detection reagents is selected such that the level of 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. 
     
     
         5 . The diagnostic panel of  claim 1  wherein the plurality of detection reagents is between two and 100 detection reagents. 
     
     
         6 . The diagnostic panel of  claim 1  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 Tables 1-32, 36-45 and 47-79 and from among the proteins identified as secreted. 
     
     
         7 . The diagnostic panel of  claim 1  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 Tables 1-32, 36-45 and 47-79 and from among the proteins identified as transmembrane. 
     
     
         8 . The diagnostic panel of  claim 1  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 Tables 1-32, 36-45 and 47-79 and from among the proteins with a specificity of 0.8 or greater. 
     
     
         9 . The diagnostic panel of  claim 1  wherein the disease affects the adrenal gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 1. 
     
     
         10 . The diagnostic panel of  claim 1  wherein the disease affects the bladder and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 2. 
     
     
         11 . The diagnostic panel of  claim 1  wherein the disease affects the bone marrow and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 3. 
     
     
         12 . The diagnostic panel of  claim 1  wherein the disease affects the brain amygdala and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 4. 
     
     
         13 . The diagnostic panel of  claim 1  wherein the disease affects the colon and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 11. 
     
     
         14 . The diagnostic panel of  claim 1  wherein the disease affects the heart and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 12. 
     
     
         15 . The diagnostic panel of  claim 1  wherein the disease affects the kidney and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 13. 
     
     
         16 . The diagnostic panel of  claim 1  wherein the disease affects the lung and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 14. 
     
     
         17 . The diagnostic panel of  claim 1  wherein the disease affects the mammary gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 15. 
     
     
         18 . The diagnostic panel of  claim 1  wherein the disease affects the peripheral blood and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 16. 
     
     
         19 . The diagnostic panel of  claim 1  wherein the disease affects the pancreas and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 17. 
     
     
         20 . The diagnostic panel of  claim 1  wherein the disease affects the peripheral blood and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 18. 
     
     
         21 . The diagnostic panel of  claim 1  wherein the disease affects the pituitary gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 19. 
     
     
         22 . The diagnostic panel of  claim 1  wherein the disease affects the prostate and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 21. 
     
     
         23 . The diagnostic panel of  claim 1  wherein the disease affects the retina and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 22. 
     
     
         24 . The diagnostic panel of  claim 1  wherein the disease affects the salivary gland and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 23. 
     
     
         25 . The diagnostic panel of  claim 1  wherein the disease affects the Small intestine and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 24. 
     
     
         26 . The diagnostic panel of  claim 1  wherein the disease affects the Spinal cord and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 25. 
     
     
         27 . The diagnostic panel of  claim 1  wherein the disease affects the spleen and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 26. 
     
     
         28 . The diagnostic panel of  claim 1  wherein the disease affects the stomach and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 27. 
     
     
         29 . The diagnostic panel of  claim 1  wherein the disease affects the testis and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 28. 
     
     
         30 . The diagnostic panel of  claim 1  wherein the disease affects the thymus and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 29. 
     
     
         31 . The diagnostic panel of  claim 1  wherein the disease affects the thyroid and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 30. 
     
     
         32 . The diagnostic panel of  claim 1  wherein the disease affects the uterus and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 32. 
     
     
         33 . The diagnostic panel of  claim 4  wherein the disease is Cushing's syndrome. 
     
     
         34 . 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 Tables 1-32, 36-45 and 47-79; 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.   
     
     
         35 . The diagnostic panel of  claim 34  wherein the plurality of detection reagents is selected such that the level of at least two 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. 
     
     
         36 . The diagnostic panel of  claim 34  wherein the plurality of detection reagents is selected such that the level of at least three 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. 
     
     
         37 . The diagnostic panel of  claim 34  wherein the plurality of detection reagents is selected such that the level of 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 organs from which the organ-specific proteins are derived is above or below a predetermined normal range. 
     
     
         38 . The diagnostic panel of  claim 34  wherein the plurality of detection reagents is between two and 100 detection reagents. 
     
     
         39 . The diagnostic panel of  claim 34  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 Tables 1-32, 36-45 and 47-79 and from among the proteins identified as secreted. 
     
     
         40 . The diagnostic panel of  claim 34  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 Tables 1-32, 36-45 and 47-79 and from among the proteins identified as transmembrane. 
     
     
         41 . The diagnostic panel of  claim 34  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 Tables 1-32, 36-45 and 47-79 and from among the proteins with a specificity of 0.8 or greater. 
     
     
         42 . The diagnostic panel of  claim 34  wherein the disease is a bladder disease and wherein the organ-specific proteins detected by the plurality of detection reagents are selected from any one or both of Tables 13 and 2. 
     
     
         43 . The diagnostic panel of  claim 34  wherein the disease is a neurological disease and wherein 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. 
     
     
         44 . The diagnostic panel of  claim 13  wherein the colon disease is colon cancer and wherein the organ-specific proteins detected by the plurality of detection reagents are selected from Table 11. 
     
     
         45 . The diagnostic panel of  claim 14  wherein the heart disease is selected from the group consisting of valvular heart disease; corpulmonale, cardiomyopathy, myocarditis, pericardial disease; vascular diseases such as atherosclerosis, acute myocardial infarction, ischemic heart disease and wherein the organ-specific proteins detected by the plurality of detection reagents are selected from Table 12. 
     
     
         46 . The diagnostic panel of  claim 1  wherein the disease affects the uterus and the organ-specific proteins detected by the plurality of detection reagents are selected from Table 32. 
     
     
         47 . The diagnostic panel of  claim 1  or  claim 34  wherein the detection reagent comprises an antibody or an antigen-binding fragment thereof. 
     
     
         48 . The diagnostic panel of  claim 1  or  claim 34  wherein the detection reagent comprises a DNA or RNA aptamer. 
     
     
         49 . The diagnostic panel of  claim 1  or  claim 34  wherein the detection reagent comprises an isotope labeled peptide. 
     
     
         50 . 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 Tables 1-32, 36-45 and 47-79 in a blood sample from the subject;   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.   
     
     
         51 . The method of  claim 50 , wherein the level of the at least two organ-specific proteins is measured using an immunoassay. 
     
     
         52 . The method of  claim 51  wherein the immunoassay comprises an ELISA. 
     
     
         53 . The method of  claim 50  wherein the level of the at least two organ-specific proteins is measured using mass spectrometry. 
     
     
         54 . The method of  claim 50  wherein the level of the at least two organ-specific proteins is measured using an aptamer capture assay. 
     
     
         55 . 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 Tables 1-32, 36-45 and 47-79 in a blood sample from the subject;   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.   
     
     
         56 . The method of  claim 55 , wherein the level of the at least two organ-specific proteins is measured using an immunoassay. 
     
     
         57 . The method of  claim 56  wherein the immunoassay comprises an ELISA. 
     
     
         58 . The method of  claim 55  wherein the level of the at least two organ-specific proteins is measured using mass spectrometry. 
     
     
         59 . The method of  claim 55  wherein the level of the at least two organ-specific proteins is measured using an aptamer capture assay. 
     
     
         60 . 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 Tables 1-32, 36-45 and 47-79 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;   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.   
     
     
         61 . The method of  claim 60  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         62 . The method of  claim 60  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         63 . The method of  claim 60  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         64 . The method of  claim 60  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         65 . The method of  claim 60  wherein the level of the at least two organ-specific proteins is measured using antibodies or antigen-binding fragments thereof specific for each protein. 
     
     
         66 . The method of  claim 65  wherein the antibodies or antigen-binding fragments thereof are monoclonal antibodies. 
     
     
         67 . The method of  claim 60  wherein the level of the at least two organ-specific proteins is measured using mass spectrometry. 
     
     
         68 . The method of  claim 60  wherein the level of the at least two organ-specific proteins is measured using an aptamer capture assay. 
     
     
         69 . The method of  claim 60  wherein the disease is prostate cancer and the at least two organ-specific proteins are selected from Table 21. 
     
     
         70 . The method of  claim 60  wherein the disease is breast cancer and the at least two organ-specific proteins are selected from Table 15. 
     
     
         71 . The method of  claim 60  wherein the disease is kidney cancer and the at least two organ-specific proteins are selected from Table 15. 
     
     
         72 . The method of  claim 60  wherein the disease is bladder cancer and the at least two organ-specific proteins are selected from Table 2. 
     
     
         73 . 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 two or more of the organ-specific protein sets provided in Tables 1-32, 36-45 and 47-79 in a blood sample from a subject determined to have a disease of interest;   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.   
     
     
         74 . The method of  claim 73  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         75 . The method of  claim 73  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         76 . The method of  claim 73  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         77 . The method of  claim 73  wherein 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 Tables 1-32, 36-45 and 47-79 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. 
     
     
         78 . 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 Tables 1-32, 36-45 and 47-79;   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.   
     
     
         79 . 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 Tables 1-32, 36-45 and 47-79;   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.   
     
     
         80 . 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.   
     
     
         81 . The method of  claim 80  wherein the prostate-specific proteins are selected from those proteins in Table 21 designated as secreted and with a specificity of 0.9 or greater. 
     
     
         82 . The method of  claim 80  wherein the prostate disease is selected from the group consisting of prostate cancer, prostatitis, and benign prostatic hyperplasia. 
     
     
         83 . The method of  claim 80  wherein the plurality of detection reagents comprises at least 2 detection reagents. 
     
     
         84 . The method of  claim 80  wherein the plurality of detection reagents comprises at least 3 detection reagents. 
     
     
         85 . The method of  claim 80  wherein the plurality of detection reagents comprises at least 4 detection reagents. 
     
     
         86 . The method of  claim 80  wherein the plurality of detection reagents comprises at least 5 detection reagents. 
     
     
         87 . The method of  claim 80  wherein the plurality of detection reagents comprises at least 6 detection reagents. 
     
     
         88 . 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 Tables 1-32, 36-45 and 47-79;   (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.   
     
     
         89 . 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 Tables 1-32, 36-45 and 47-79;   (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.   
     
     
         90 . A method of imaging an organ, tissue or cells derived from an organ or tissue, comprising providing an organ-specific probe that specifically recognizes a sequence of any one or more of the sequences set forth in Tables 1-32, 36-45 and 47-79, wherein said probe has attached thereto a label, said label comprising a detectable marker, administering said probe to an animal and detecting the location of said probe. 
     
     
         91 . An imaging probe comprising an organ-specific probe that specifically recognizes a sequence of any one or more of the sequences set forth in Tables 1-32, 36-45 and 47-79, wherein said probe has attached thereto a label, said label comprising a detectable marker. 
     
     
         92 . A method of targeting an organ, tissue, or cell comprising providing an organ-specific probe that specifically recognizes a sequence of any one or more of the sequences set forth in Tables 1-32, 36-45 and 47-79, wherein said probe has attached thereto a therapeutic agent, said therapeutic agent comprising a radioisotope or cytotoxic agent. 
     
     
         93 . A targeting agent comprising an organ-specific probe that specifically recognizes a sequence of any one or more of the sequences set forth in Tables 1-32, 36-45 and 47-79, wherein said probe has attached thereto a therapeutic agent, said therapeutic agent comprising a radioisotope or cytotoxic agent. 
     
     
         94 . The diagnostic panel of  claim 1  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 Tables 47-79 and from among the proteins identified by MPSS data and SBS data. 
     
     
         95 . The diagnostic panel of  claim 34  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 Tables 47-79 and from among the proteins identified by MPSS data and SBS data.