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

• US 8,055,452 B2
• Filed: 10/30/2009
• Issued: 11/08/2011
• Est. Priority Date: 11/09/2001
• Status: Expired due to Fees

• Current Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Original Assignee: Life Technologies Corporation (Thermo Fisher Scientific Incorporated)
• Inventors: Bevilacqua, Michael P., Bankaitis-Davis, Danute M., Cheronis, John C., Tryon, Victor
• Primary Examiner(s): ZEMAN, MARY K
• Application Number:
  US12/609,578
• Publication Number:
  US 20100086935A1
• Time in Patent Office: 739 Days
• Field of Search: None
• US Class Current: 702/19
• CPC Class Codes: G01N 2800/042 Disorders of carbohydrate metabolism, e.g. diabetes, glucose metabolism
• 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 20/00 ICT specially adapted for functional genomics or proteomics, e.g. genotype-phenotype associations
• 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: G16Z 99/00 Subject matter not provided for in other main groups of this subclass
• 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

A method provides an index that is indicative of the state of a subject, as to a biological condition, based on a sample from the subject. An embodiment of this method includes: deriving from the sample a profile data set, the profile data set including a plurality of members, each member being a quantitative measure of the amount of a distinct RNA or protein constituent in a panel of constituents selected so that measurement of the constituents enables evaluation of the biological condition; and in deriving the profile data set, achieving such measure for each constituent under measurement conditions that are substantially repeatable; and applying values from the profile data set to an index function that provides a mapping from an instance of a profile data set into a single-valued measure of biological condition, so as to produce an index pertinent to the biological condition of the subject.

Claims

1. A method of predicting change in a biological condition of a subject as a result of exposure to an agent, the method comprising:

a) producing a first index for a sample from the subject in the absence of the agent, the sample providing a source of RNAs comprising;

i) using amplification for quantitatively measuring the amount of RNA of at least two constituents from any one of Tables 1 through 12 from the sample from the subject, wherein a panel of constituents is selected so that measurement conditions of the constituents enables evaluation of said biological condition and wherein the measures of all constituents in the panel form a first profile data set, wherein said amplification for each constituent is under conditions that are (1) within a degree of repeatability of better than five percent; and

(2) the efficiencies of amplification are within two percent;

ii) using amplification for quantitatively 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

iii) applying values from the first profile data set to an index function derived using latent class modeling, thereby providing a single-valued measure of the biological condition so as to produce an index pertinent to the biological condition of the subject;

wherein the index function also uses data from the normative baseline profile data set,

b) producing a second index for a second sample from the subject in the presence of the agent, the second index based on the same panel of constituents; and

c) using the first and second indices to predict change in the biological condition of the subject as a result of exposure to the agent.

2. A method according to claim 1, wherein the agent is a compound.

3. A method according to claim 2, wherein the compound is therapeutic.