Identification, monitoring and treatment of disease and characterization of biological condition using gene expression profiles

• US 6,960,439 B2
• Filed: 11/08/2002
• Issued: 11/01/2005
• Est. Priority Date: 06/28/1999
• Status: Expired due to Term

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Source Precision Medicine Inc.
• Inventors: Bankaitis-Davis, Danute M., Cheronis, John C., Tryon, Victor, Bevilacqua, Michael
• Primary Examiner(s): Allen, Marianne P.
• Application Number:
  US10/291,225
• Publication Number:
  US 20040133352A1
• Time in Patent Office: 1,089 Days
• Field of Search: 435/6, 702/19, 702/20
• US Class Current: 435/6.11
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• CPC Class Codes: G01N 33/5088 of vertebrates
• CPC Class Codes: G01N 33/57415 of breast
• CPC Class Codes: G01N 33/6803 General methods of protein analysis not limited to specific proteins or families of proteins
• CPC Class Codes: G01N 33/6863 Cytokines, i.e. immune system proteins modifying a biological response such as cell growth proliferation or differentiation, e.g. TNF, CNF, GM-CSF, lymphotoxin, MIF or their receptors
• CPC Class Codes: G01N 33/6869 Interleukin
• CPC Class Codes: G01N 33/6893 related to diseases not provided for elsewhere
• CPC Class Codes: G16B 25/00 ICT specially adapted for hybridisation; ICT specially adapted for gene or protein expression
• CPC Class Codes: G16B 25/10 Gene or protein expression profiling; Expression-ratio estimation or normalisation
• 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

Gene expression data, in particular gene expression profiles, are created and used in the identification, monitoring and treatment of disease and characterization of biological conditions. Profile data sets are derived from subject samples and include quantitative substantially repeatable measures of a distinct amount of RNA or protein constituent in a panel selected to enable evaluation of a biological condition. Such profile data sets may be used to provide an index indicative of the biological state of a subject, which may be compared to a normative value of the index determined with respect to a relevant population of subjects.

Claims

1. A method, for evaluating a biological condition of a subject, based on a sample from the subject, the sample providing a source of RNAs, the method comprising:

using amplification for measuring the amount of RNA of at least two constituents from any one of Tables 1 through 12 from the sample of the subject, where

a panel of constituents is selected so that measurement of the constituents enables evaluation of the biological condition and wherein the measures of all constituents in the panel form a first profile data set,

using amplification for measuring the amount of RNA of all constituents in said panel wherein the measures of all constituents in the panel are from a relevant population of subjects and form a normative baseline profile data set; and

producing a calibrated profile data set for said panel, wherein each member of the calibrated profile data set is a function of a member of the first profile data set and the corresponding member of the normative baseline profile data set, wherein the measures for each constituent are performed under measurement conditions that are substantially repeatable and the efficiencies of amplification for all constituents are substantially similar and the calibrated profile data set provides a measure of the biological condition of the subject.

2. A method according to claim 1, wherein efficiencies of amplification, expressed as a percent, for all constituents lie within a range of approximately 2 percent.

3. A method according to claim 1, wherein measurement conditions are repeatable so that such measure for each constituent has a coefficient of variation, on repeated derivation of such measure from the sample, that is less than approximately 3 percent.

4. A method according to claim 1, wherein efficiencies of amplification, expressed as a percent, for all constituents lie within a range of approximately 1 percent.

5. A method according to claim 2, wherein measurement conditions are repeatable so that such measure for each constituent has a coefficient of variation, on repeated derivation of such measure from the sample, that is less than approximately 3 percent.

6. A method according to claim 1, wherein measurement conditions are repeatable so that such measure for each constituent has a coefficient of variation, on repeated derivation of such measure from the sample, that is less than approximately 3 percent.

7. A method according to claim 1, wherein the panel includes at least three constituents.

8. A method according to claim 1, wherein the panel has fewer than approximately 500 constituents.

9. A method according claim 1, wherein the biological condition is inflammation and the panel of constituents includes at least two of the constituents of the Inflammation Gene Expression Panel of Table 1.

10. A method according to claim 1, wherein the biological condition is diabetes and the panel of constituents includes at least two of the constituents of the Diabetes Gene Expression Panel of Table 2.

11. A method according to claim 1, wherein the biological condition is prostate health or disease and the panel of constituents includes at least two of the constituents of the Prostate Gene Expression Panel of Table 3.

12. A method according to claim 1, wherein the biological condition is manifested in skin and the panel of constituents includes at least two of the constituents of the Skin Response Gene Expression Panel of Table 4.

13. A method according to claim 1, wherein the biological condition is liver metabolism and disease and the panel of constituents includes at least two of the constituents of the Liver Metabolism and Disease Gene Expression Panel of Table 5.

14. A method according to claim 1, wherein the biological condition is vascular and the panel of constituents includes at least two of the constituents of the Endothelial Gene Expression Panel of Table 6.

15. A method according to claim 1, wherein the biological condition is abnormal cell development and the panel of constituents includes at least two of the Cell Health and Apoptosis Gene Expression Panel of Table 7.

16. A method according to claim 1, wherein the biological condition is inflammation and the panel of constituents includes at least two of the constituents of the Cytokine Gene Expression Panel of Table 8.

17. A method according to claim 1, wherein the biological condition is inflammation and the panel of constituents includes at least two of the constituents of the TNF/IL1 Inhibition Gene Expression Panel of Table 9.

18. A method according to claim 1, wherein the biological condition is inflammation and the panel of constituents includes at least two, of the constituents of the Chemokine Gene Expression Panel of Table 10.

19. A method according to claim 1, wherein the biological condition is cancer and the panel of constituents includes at least two of the constituents of the Breast Cancer Gene Expression Panel of Table 11.

20. A method according to claim 1, wherein the biological condition is infectious disease and the panel of constituents includes at least two of the constituents of the Infectious Disease Gene Expression Panel of Table 12.

21. A method according to claim 1, wherein the relevant population is a population of healthy subjects.

22. A method according to claim 1, wherein the relevant population has in common a property that is at least one of age group, gender, ethnicity, geographic location, diet, medical disorder, clinical indicator, medication, physical activity, body mass, and environmental exposure.

23. A method, for evaluating a biological condition characterized by inflammation of a subject, based on a sample from the subject, the sample providing a source of RNAs, the method comprising:

using amplification for measuring the amount of RNA of constituents from the sample of the subject, where a panel of constituents is selected so that measurement of the constituents enables evaluation of the biological condition and wherein the measures of all constituents in the panel form a first profile data set,

using amplification for measuring the amount of RNA of all constituents in said panel wherein the measures of all constituents in the panel are from a relevant population of subjects and form a normative baseline profile data set; and

producing a calibrated profile data set for said panel, wherein each member of the calibrated profile data set is a function of a member of the first profile data set and the corresponding member of the normative baseline profile data set, wherein the measures for each constituent are performed under measurement conditions that are substantially repeatable and the efficiencies of amplification for all constituents are substantially similar and the calibrated profile data set provides a measure of the biological condition of the subject.

24. A method according to claim 23, the panel including at least three of the constituents of the Inflammation Gene Expression Panel of Table 1.

25. A method according to claim 23, the panel including at least four of the constituents of the Inflammation Gene Expression Panel of Table 1.

26. A method according to claim 23, the panel including at least five of the constituents of the Inflammation Gene Expression Panel of Table 1.

27. A method according to claim 23, the panel including at least six of the constituents of the Inflammation Gene Expression Panel of Table 1.