IP Library Granted Patent US 8,068,987
Granted Patent B2
US 8,068,987 · App. 10/218,880 · Granted Nov 29, 2011

Method and system for profiling biological systems

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Quick Facts
Patent No.
US 8,068,987
App. No.
10/218,880
Granted
Nov 29, 2011
Kind
B2
Abstract

The present invention provides methods and systems for developing profiles of a biological system based on the discernment of similarities, differences, and/or correlations between biomolecular components of a plurality of biological samples. Preferably, the method comprises utilizing hierarchical multivariate analysis of spectrometric data at one or more levels of correlation.

Claims (54)

1. A method of profiling a state of a biological system in an animal, the method comprising:

evaluating with a suitably programmed computer a plurality of data sets with a multivariate analysis and correlating spectral features to generate a profile of one or more biomarkers in response to one or more correlations, the profile characterizing a state of the biological system,

wherein the multivariate analysis comprises principal component analysis, and

the plurality of data sets comprise at least two different types of spectrometric measurements of a sample of a biological system, wherein the spectrometric measurements are from more than one spectrometric technique comprising mass spectrometry, nuclear magnetic resonance spectrometry, liquid chromatography, gas chromatography, high performance liquid chromatography, or capillary electrophoresis; and

displaying at least a portion of data relevant to the profile.

2. The method of claim 1 , wherein the multivariate analysis further comprises at least one of discriminant analysis, principal component analysis with discriminant analysis, canonical correlation, kernel principal component analysis, non-linear principal component analysis, factor analysis, multidimensional scaling, and cluster analysis.

3. The method of claim 1 , wherein the multivariate analysis comprises a hierarchical cascade of two or more multivariate analyses.

4. The method of claim 1 , wherein the plurality of data sets are derived from a biological sample type selected from the group consisting of blood, blood plasma, blood serum, cerebrospinal fluid, bile, saliva, synovial fluid, pleural fluid, pericardial fluid, peritoneal fluid, feces, nasal fluid, ocular fluid, intracellular fluid, intercellular fluid, lymph fluid, and urine.

5. The method of claim 1 , wherein the plurality of data sets are derived from a biological sample type selected from the group consisting of liver cells, epithelial cells, endothelial cells, kidney cells, prostate cells, blood cells, lung cells, brain cells, skin cells, adipose cells, tumor cells, and mammary cells.

6. The method of claim 1 , wherein the sample comprises samples taken at different times for the same organism.

7. The method of claim 1 , further comprising the step of comparing the profile to a database of profiles.

8. The method of claim 1 , wherein evaluating comprises evaluating a quality factor for data sets of two or more spectrometric measurement techniques to determine differences arising from spectrometric measurement technique.

9. The method of claim 1 , wherein the state of the biological system comprises a disease state.

10. The method of claim 1 , wherein the state of the biological system comprises a response to a pharmacological agent.

11. The method of claim 1 , wherein the state of the biological system comprises a response to at least one of age, environment, and stress.

12. An article of manufacture having a computer-readable medium with computer-readable instructions embodied thereon for performing the method of claim 1 .

13. A system for profiling a state of a biological system in an animal, the system comprising:

(a) one or more spectrometric instruments adapted to provide at least one data set comprising at least two different types of spectrometric measurements of a sample of a biological system, wherein the spectrometric measurements are from at least two different spectrometric techniques comprising mass spectrometry, nuclear magnetic resonance spectrometry, liquid chromatography, gas chromatography, high performance liquid chromatography, or capillary electrophoresis; and

(b) a data processing device in communication with the one or more spectrometric instruments, wherein the data processing device embodies logic adapted to

(i) evaluate the at least one data set with a multivariate analysis and correlate spectral features to generate a profile of one or more biomarkers in response to one or more correlations, the profile characterizing a state of the biological system, wherein the multivariate analysis comprises principal component analysis.

14. The system of claim 13 , wherein the system further comprises an external database accessible by the data processing device.

15. The method of claim 1 wherein the plurality of data sets is derived from one biological sample type.

16. The method of claim 1 wherein the plurality of data sets is derived from one biological sample type that is treated differently.

17. The method of claim 1 wherein the biological system is in an animal.

18. The method of claim 1 , wherein the plurality of data sets comprise spectrometric measurements of a biomolecule component type.

19. The method of claim 18 , wherein the biomolecule component type is a gene transcript, a protein, or a metabolite.

20. A method of profiling a state of a biological system in an animal, the method comprising:

analyzing a sample of a biological system to provide a plurality of data sets comprising at least two different types of spectrometric measurements obtained from at least two different spectrometric techniques comprising mass spectrometry, nuclear magnetic resonance spectrometry, liquid chromatography, gas chromatography, high performance liquid chromatography, or capillary electrophoresis; and

evaluating with a suitably programmed computer the plurality of data sets with a multivariate analysis and correlating spectral features to generate a profile of one or more biomarkers in response to one or more correlations, the profile characterizing a state of the biological system, wherein the multivariate analysis comprises principal component analysis.

21. The method of claim 20 , wherein the multivariate analysis further comprises at least one of discriminant analysis, principal component analysis with discriminant analysis, canonical correlation, kernel principal component analysis, non-linear principal component analysis, factor analysis, multidimensional scaling, and cluster analysis.

22. The method of claim 20 , wherein the multivariate analysis comprises a hierarchical cascade of two or more multivariate analyses.

23. The method of claim 20 , wherein the plurality of data sets are derived from a biological sample type selected from the group consisting of blood, blood plasma, blood serum, cerebrospinal fluid, bile, saliva, synovial fluid, pleural fluid, pericardial fluid, peritoneal fluid, feces, nasal fluid, ocular fluid, intracellular fluid, intercellular fluid, lymph fluid, and urine.

24. The method of claim 20 , wherein the plurality of data sets are derived from a biological sample type selected from the group consisting of liver cells, epithelial cells, endothelial cells, kidney cells, prostate cells, blood cells, lung cells, brain cells, skin cells, adipose cells, tumor cells, and mammary cells.

25. The method of claim 20 , wherein the sample comprises samples taken at different times for the same organism.

26. The method of claim 20 , further comprising the step of comparing the profile to a database of profiles.

27. The method of claim 20 , wherein evaluating comprises evaluating a quality factor for data sets of two or more spectrometric measurement techniques to determine differences arising from spectrometric measurement technique.

28. The method of claim 20 , wherein the state of the biological system comprises a disease state.

29. The method of claim 20 , wherein the state of the biological system comprises a response to a pharmacological agent.

30. The method of claim 20 , wherein the state of the biological system comprises a response to at least one of age, environment, and stress.

31. The method of claim 20 wherein the plurality of data sets is derived from one biological sample type.

32. The method of claim 20 wherein the plurality of data sets is derived from one biological sample type that is treated differently.

33. The method of claim 20 wherein the biological system is in an animal.

34. The method of claim 20 , wherein the plurality of data sets comprise spectrometric measurements of a biomolecule component type.

35. The method of claim 34 , wherein the biomolecule component type is a gene transcript, a protein, or a metabolite.

36. An article of manufacture having a computer-readable medium with computer-readable instructions embodied thereon for performing the method of claim 20 .

37. A method of profiling a state of an animal, the method comprising:

evaluating with a suitably programmed computer a plurality of data sets with a multivariate analysis comprising principal component analysis and correlating spectral features to generate a profile of one or more biomarkers in response to one or more correlations, the profile characterizing a state of the animal,

wherein the plurality of data sets comprise at least two different types of spectrometric measurements of a sample of an animal,

the spectrometric measurements comprise measurements of a gene transcript, a protein, or a metabolite, and

the spectrometric measurements are from more than one spectrometric technique comprising mass spectrometry, nuclear magnetic resonance spectrometry, liquid chromatography, gas chromatography, high performance liquid chromatography, or capillary electrophoresis; and

displaying at least a portion of data relevant to the profile.

38. A method of profiling a state of an animal, the method comprising:

analyzing a sample of an animal to provide a plurality of data sets, the plurality of data sets comprising at least two different types of spectrometric measurements obtained using at least two different spectrometric techniques comprising mass spectrometry, nuclear magnetic resonance spectrometry, liquid chromatography, gas chromatography, high performance liquid chromatography, or capillary electrophoresis, wherein the spectrometric measurements comprise measurements of a gene transcript, a protein, or a metabolite; and

evaluating with a suitably programmed computer the plurality of data sets with a multivariate analysis comprising principal component analysis and correlating spectral features to generate a profile of one or more biomarkers in response to one or more correlations, the profile characterizing a state of the animal.

Assignments (6)
RELEASE OF SECURITY INTEREST Recorded Dec 19, 2008
From: SILICON VALLEY BANK
To: BG MEDICINE, INC.
Reel/Frame 022012/0083 →
SECURITY AGREEMENT Recorded Nov 28, 2007
From: BG MEDICINE, INC.
To: SILICON VALLEY BANK
Reel/Frame 020166/0868 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 9, 2006
From: NEDERLANDSE ORGANISATIE VOOR TOEGEPAST-NATUURWETENSCHAPPELIIJK ONDERZOEK TNO
To: BG MEDICINE, INC.
Reel/Frame 017436/0426 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 16, 2005
From: VERHEIJ, ELWIN ROBBERT
To: NEDERLANDSE ORGANISATIE VOOR TOEGEPAST-NATUURWETENSCHAPPELIJK ONDERZOEK TNO
Reel/Frame 016563/0102 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded May 16, 2005
From: AFEYAN, NOUBAR B.; VAN DER GREEF, JAN; REGNIER, FREDERICK E.; ADOURIAN ARAM S.; NEUMANN, ERIC K.; ORESIC, MATEJ
To: BG MEDICINE, INC.
Reel/Frame 016563/0328 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Dec 10, 2003
From: DISETRONIC LICENSING AG
To: DISETRONIC SERVICES AG
Reel/Frame 014243/0598 →