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

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.

1 . A method of providing an index that is indicative of the inflammatory state 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 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;    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    applying values from the first profile data set to an index function I=ΣC i M i   P(i)  wherein I is the index, M is the value of the member i of the profile data set, C; is a constant, and P(i) is a power to which M i  is raised, the sum being formed for all integral values of i up to the number of members in the data set, 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.    
   
   
       2 . A method of providing an index according to  claim 1  wherein, in deriving the first profile data set and the normative baseline data set, 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.  
   
   
       3 . A method of determining at least one of (i) an effective dose of an agent to be administered to a subject and (ii) a schedule for administration of an agent to a subject, the method comprising: 
 producing an index according to  claim 1 , and using the index as an indicator in establishing at least one of the effective dose and the schedule.    
   
   
       4 . A method of guiding a decision to continue or modify therapy for a biological condition of a subject, the method comprising: 
 producing an index according to  claim 1  and    using the index to guide the decision to modify therapy for the biological condition of the subject.    
   
   
       5 . A method of predicting change in a biological condition of a subject as a result of exposure to an agent, the method comprising: 
 producing a first index for a sample from the subject in the absence of the agent according to  claim 1;     producing a second index for a second sample from the subject in the presence of the agent, the second index based on the same Signature Panel; and    using the first and second indices to predict change in the biological condition of the subject as a result of exposure to the agent.    
   
   
       6 . A method according to  claim 5 , wherein the agent is a compound.  
   
   
       7 . A method according to  claim 6 , wherein the compound is therapeutic.  
   
   
       8 . A method of evaluating a property of an agent, the property being at least one of purity, potency, quality, efficacy or safety, the method comprising: 
 producing an index according to  claim 1;  and    using the index in evaluating at least one the purity, potency, quality, efficacy or safety of the agent.