Organ-Specific Proteins and Methods of Their Use
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.
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.