Systems and methods for characterizing a biological condition or agent using selected gene expression profiles

Abstract

Methods are provided for evaluating a biological condition of a subject using a calibrated profile data set derived from a data set having a plurality of members, each member being a quantitative measure of the amount of a subject's RNA or protein as distinct constituents in a panel of constituents. The biological condition may be a naturally occurring physiological state or may be responsive to treatment of the subject with one or more agents. Calibrated profile data sets may be used as a descriptive record for an agent.

We claim:  
     
         1 . A method of conducting a clinical trial of an agent, the method comprising: 
 a. administering one of a placebo or the agent to each subject of a pool of subjects; and    b. using quantitative gene expression to evaluate an effect of such administration, wherein using quantitative gene expression analysis includes quantitatively measuring the amount of a distinct RNA constituent in a panel of constituents selected so that measurement enables evaluation of a biological condition of each subject in the pool of subjects, based on a sample from each subject, the sample providing a source of RNAs, wherein such measure for each constituent is obtained under measurement conditions that are substantially reproducible.    
     
     
         2 . A method according to  claim 1 , wherein the pool of subjects is selected using quantitative gene expression analysis on a plurality of candidate subjects to identify those subjects likely to show a response to the agent.  
     
     
         3 . A method according to  claim 1  for evaluating candidate subjects to identify those subjects likely to show a response to the agent based on a sample from each candidate subject, the sample providing a source of RNAs, the method further comprising: 
 a. quantitatively measuring the amount of a distinct RNA constituent in a panel of constituents selected so that measurement enables evaluation of a biological condition of each subject and resulting in a baseline set of values for each subject;  
 b. comparing the baseline values to a set of second values contained in a library of baseline profile data sets for response to agents; the library containing a plurality of baseline profile data sets grouped according to a predetermined response to agents; and  
 c. identifying subjects likely to show a response to the agent.  
 
     
     
         4 . A method according to  claim 2  for evaluating candidate subjects to identify those subjects likely to show a response to the agent based on a sample from each candidate subject, the sample providing a source of RNAs, the method further comprising: 
 a. quantitatively measuring the amount of a distinct RNA constituent in a panel of constituents selected so that measurement enables evaluation of a biological condition of each subject and resulting in a baseline set of values for each subject;  
 b. comparing the baseline values to a set of second values contained in a library of baseline profile data sets for response to agents; the library containing a plurality of baseline profile data sets grouped according to a predetermined response to agents; and  
 c. identifying subjects likely to show a response to the agent.  
 
     
     
         5 . A method according to  claim 1 , further comprising using quantitative gene expression to determine at least one of a dosage and a dosage range.  
     
     
         6 . A method according to  claim 1 , further comprising using quantitative gene expression analysis to assist in determining at least one of efficacy and toxicity of the agent.  
     
     
         7 . A method according to  claim 1 , further comprising: selecting the subject for a clinical trial according to the biological condition of the subject, so as to determine predictively whether the subject will respond to a test compound if the compound has a predetermined biological activity.  
     
     
         8 . A method according to  claim 7 , wherein the test compound is a pharmaceutical agent.  
     
     
         9 . A method according to  claim 7  where the test compound is a nutraceutical agent.  
     
     
         10 . A method according to  claim 4 , further comprising using quantitative gene expression to determine at least one of a dosage and a dosage range.  
     
     
         11 . A method according to  claim 4 , further comprising using quantitative gene expression analysis to assist in determining at least one of efficacy and toxicity of the agent.  
     
     
         12 . A method according to  claim 4 , further comprising: selecting the subject for a clinical trial according to the biological condition of the subject, so as to determine predictively whether the subject will respond to a test compound if the compound has a predetermined biological activity.  
     
     
         13 . A method according to  claim 8 , wherein the test compound is a pharmaceutical agent.  
     
     
         14 . A method according to  claim 8  where the test compound is a nutraceutical agent.