Multiparameter analysis for drug response and related methods

Abstract

The invention provides a method of determining a comparative expression profile in an individual by comparing the expression levels of a sample of molecules in a population of molecules in a specimen from the individual with a health-associated reference expression region of the sample of molecules, wherein expression levels within the health-associated reference expression region indicate a reference expression profile and wherein expression levels outside the health-associated reference expression region indicate a perturbed expression profile. The invention also provides methods of diagnosing a disease or a health state in an individual by comparing the expression level of a sample of molecules in a specimen from the individual with a health-associated reference expression region of the sample of molecules. The invention additionally provides a method of classifying a population by drug responsiveness.

1 - 16 . (canceled) 
     
     
         17 . A method of predicting a drug response in an individual, comprising:
 (a) determining a multidimensional coordinate point representative of the expression levels of a sample of molecules in a specimen from an individual treated with a drug;   (b) comparing said multidimensional coordinate point to a drug response-associated reference expression region for individuals treated with said drug; and   (c) determining if said multidimensional coordinate point for said individual is within or outside said drug response-associated reference expression region, wherein said multidimensional coordinate point within said drug response-associated reference expression region indicates said individual has a substantially similar response to said drug as individuals in a drug response reference population used for said drug response-associated reference expression region.   
     
     
         18 . The method of  claim 17 , further comprising the step of inputting the expression level of said molecules in said sample. 
     
     
         19 . The method of  claim 17 , further comprising the step of determining the expression level of said molecules in said sample. 
     
     
         20 . The method of  claim 19 , wherein the expression levels of said sample of molecules in said specimen are determined by direct comparison with reference expression levels correlated with health-associated reference expression intervals of said molecules in said sample. 
     
     
         21 . The method of  claim 17 , further comprising the step of contacting said specimen with a target. 
     
     
         22 . The method of  claim 17 , wherein said specimen is selected from the group consisting of leukocytes, blood, and serum. 
     
     
         23 . The method of  claim 21 , wherein said target is an array. 
     
     
         24 . The method of  claim 17 , wherein said molecules in said specimen comprise nucleic acids. 
     
     
         25 . The method of  claim 21 , wherein said target comprises nucleic acid ligands. 
     
     
         26 . The method of  claim 17 , wherein said molecules in said specimen comprise polypeptides. 
     
     
         27 . The method of  claim 21 , wherein said target comprises antibody ligands. 
     
     
         28 . The method of  claim 17 , wherein said molecules in said specimen comprise small molecules. 
     
     
         29 . A method of predicting a drug response in an individual, comprising:
 (a) determining a multidimensional coordinate point representative of the expression levels of a sample of molecules in a specimen comprising leukocytes from an individual treated with a drug;   (b) comparing said multidimensional coordinate point to a drug response-associated reference expression region for individuals treated with said drug; and   (c) determining if said multidimensional coordinate point for said individual is within or outside said drug response-associated reference expression region, wherein said multidimensional coordinate point within said drug response-associated reference expression region indicates said individual has a substantially similar response to said drug as individuals in a drug response reference population used for said drug response-associated reference expression region.   
     
     
         30 . A method of categorizing drug responsiveness in a population, comprising:
 (a) determining a multidimensional coordinate point representative of the expression levels of a sample of molecules in specimens from a population of individuals treated with a drug;   (b) identifying a first group of individuals having a substantially similar response to said drug; and   (c) determining a drug response-associated reference expression region of said first group of individuals using said multidimensional coordinate points of said first group of individuals, thereby categorizing the drug responsiveness of said first group of individuals.   
     
     
         31 . The method of  claim 30 , further comprising the steps of:
 (d) identifying a second group of individuals having a substantially similar response to said drug, said drug response in said second group being different than the drug response of said first group; and   (e) determining a drug response-associated reference expression region of said second group of individuals using said multidimensional coordinate points of said second group of individuals, thereby categorizing the drug responsiveness of said second group of individuals.   
     
     
         32 . The method of  claim 31 , further comprising optionally repeating steps (d) and (e) one or more times for an additional group of individuals having a substantially similar response to said drug, said drug response in said additional group of individuals being different than the drug response of identified groups. 
     
     
         33 . The method of  claim 30 , further comprising the step of inputting the expression level of said molecules in said sample. 
     
     
         34 . The method of  claim 30 , further comprising the step of determining the expression level of said molecules in said sample. 
     
     
         35 . The method of  claim 34 , wherein the expression levels of said sample of molecules in said specimen are determined by direct comparison with reference expression levels correlated with health-associated reference expression intervals of said molecules in said sample. 
     
     
         36 . The method of  claim 30 , further comprising the step of contacting said specimen with a target. 
     
     
         37 . The method of  claim 30 , wherein said specimen is selected from the group consisting of leukocytes, blood, and serum. 
     
     
         38 . The method of  claim 36 , wherein said target is an array. 
     
     
         39 . The method of  claim 30 , wherein said molecules in said specimen comprise nucleic acids. 
     
     
         40 . The method of  claim 36 , wherein said target comprises nucleic acid ligands. 
     
     
         41 . The method of  claim 30 , wherein said molecules in said specimen comprise polypeptides. 
     
     
         42 . The method of  claim 36 , wherein said target comprises antibody ligands. 
     
     
         43 . The method of  claim 30 , wherein said molecules in said specimen comprise small molecules.