Methods for identifying and using organ-specific proteins in blood

• US 9,234,895 B2
• Filed: 08/08/2012
• Issued: 01/12/2016
• Est. Priority Date: 01/27/2005
• Status: Active Grant

• Current Assignee: Institute for System Biology
• Original Assignee: Institute for System Biology
• Inventors: Hood, Leroy, Lin, Biaoyang
• Primary Examiner(s): Cheu, Jacob
• Application Number:
  US13/570,096
• Publication Number:
  US 20130045873A1
• Time in Patent Office: 1,252 Days
• Field of Search: None
• US Class Current: 1/1
• CPC Class Codes: G01N 33/68 involving proteins, peptides or amino acids involving lipoproteins G01N33/92
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G06V 20/69 Microscopic objects, e.g. biological cells or cellular parts
• CPC Class Codes: Y02A 90/10 Information and communication technologies [ICT] supporting adaptation to climate change, e.g. for weather forecasting or climate simulation

Abstract

The present invention relates generally to methods for identifying organ-specific secreted proteins and for identifying organ-specific molecular blood fingerprints therefrom. As such, the present invention provides compositions comprising such proteins, detection reagents for detecting such proteins, and panels, and arrays for determining organ-specific molecular blood fingerprints.

Claims

1. A method for diagnosing a biological condition of an organ in a subject comprising measuring the level of a plurality of organ-specific proteins in the blood of the subject, wherein the plurality of organ-specific proteins comprises at least 10 organ-specific proteins, wherein the organ-specific proteins are secreted from the same organ or specific to the same organ and wherein the levels of the plurality of organ-specific proteins together provide a fingerprint for the biological condition of the organ for diagnosis in the subject.

2. The method of claim 1 wherein a statistically significant altered level in one or more of the organ-specific proteins as compared to a predetermined normal level classifies the subject as having a perturbation from the normal biological state.

3. The method of claim 1 wherein said fingerprint is measured in the blood, serum or plasma of the subject.

4. The method of claim 1 wherein the level of the plurality of organ-specific proteins is measured using a method selected from the group consisting of mass spectrometry, an immunoassay, Western blot, microfluidics/nanotechnology sensors, and aptamer capture assay.

5. The method of claim 4 wherein the level of the plurality of organ-specific proteins is measured using tandem mass spectrometry.

6. The method of claim 4 wherein the level of the plurality of organ-specific proteins is measured using ELISA.

7. The method of claim 1 wherein the plurality of organ-specific proteins comprises about 20 organ-specific proteins.

8. The method of claim 1 wherein the biological condition affects the prostate and wherein the organ-specific proteins are prostate-specific proteins.

9. The method of claim 1 wherein the biological condition affects the breast and wherein the organ-specific proteins are breast-specific proteins.

15. The method of claim 1, wherein each organ-specific protein is expressed in the organ at a level at least 1.5 fold as compared to other organs.

16. The method of claim 1, wherein each organ-specific protein is expressed in the organ at a level at least 2.5 fold as compared to other organs.

17. The method of claim 1, wherein each organ-specific protein is expressed at a level of at least 3 copies/million in the organ but is expressed at less than 3 copies/million in other organs.

10. A method for detecting perturbation of a normal biological state of an organ in a subject comprising, (a) contacting a blood sample from the subject with a plurality of detection reagents each specific for an organ-specific protein secreted into blood, wherein the plurality of detection reagents comprises at least 10 detection reagents, wherein each organ-specific protein is secreted from the same organ;

(b) measuring the amount of the organ-specific protein detected in the blood sample by each detection reagent;

(c) comparing the amount of the organ-specific protein detected in the blood sample by each detection reagent to a predetermined 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 of the organ in the subject.

11. The method of claim 10 wherein the plurality of detection reagents comprises about 20 detection reagents.

12. The method of claim 10 wherein the perturbation comprises perturbation of the prostate and wherein the organ-specific proteins are prostate-specific proteins.

13. The method of claim 10 wherein the perturbation comprises perturbation of the liver and wherein the organ-specific proteins are liver-specific proteins.

14. The method of claim 10 wherein the perturbation comprises perturbation of the breast and wherein the organ-specific proteins are breast-specific proteins.

18. The method of claim 10, wherein each organ-specific protein is expressed in the organ at a level at least 1.5 fold as compared to other organs.

19. The method of claim 10, wherein each organ-specific protein is expressed in the organ at a level at least 2.5 fold as compared to other organs.

20. The method of claim 10, wherein each organ-specific protein is expressed at a level of at least 3 copies/million in the organ but is expressed at less than 3 copies/million in other organs.

21. A method for diagnosing a biological condition of an organ in a subject comprising measuring the level of a plurality of organ-specific proteins in the blood of the subject, wherein the plurality of organ-specific proteins comprises at least 10 organ-specific proteins, wherein each organ-specific protein is secreted from the same organ or specific to the same organ, wherein each organ-specific protein is expressed in the organ at a level at least 2.5 fold as compared to other organs, wherein each organ-specific protein is expressed at a level of at least 3 copies/million in the organ but is expressed at less than 3 copies/million in other organs, and wherein the levels of the plurality of organ-specific proteins together provide a fingerprint for the biological condition of the organ for diagnosis in the subject.

22. A method for detecting perturbation of a normal biological state of an organ in a subject comprising, (a) contacting a blood sample from the subject with a plurality of detection reagents each specific for an organ-specific protein secreted into blood, wherein the plurality of detection reagents comprises at least 10 detection reagents, wherein each organ-specific protein is secreted from the same organ, wherein each organ-specific protein is expressed in the organ at a level at least 2.5 fold as compared to other organs, wherein each organ-specific protein is expressed at a level of at least 3 copies/million in the organ but is expressed at less than 3 copies/million in other organs;

(b) measuring the amount of the organ-specific protein detected in the blood sample by each detection reagent;

(c) comparing the amount of the organ-specific protein detected in the blood sample by each detection reagent to a predetermined 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 of the organ in the subject.

23. A method for detecting perturbation of a normal biological state of an organ in a subject comprising measuring the level of a plurality of organ-specific proteins in the blood of the subject, wherein the plurality of organ-specific proteins comprises at least 10 organ-specific proteins, wherein each organ-specific protein is secreted from the same organ or specific to the same organ, wherein each organ-specific protein is expressed in the organ at a level at least 2.5 fold as compared to other organs, wherein each organ-specific protein is expressed at a level of at least 3 copies/million in the organ but is expressed at less than 3 copies/million in other organs, and wherein a statistically significant altered level in one or more of the organ-specific proteins as compared to a predetermined normal level classifies the subject as having a perturbation of the organ from the normal biological state.