Method for personalized selection of a drug for a subject

Abstract

The present invention relates to a method and a system for selecting a drug customized on the basis of individual protein information by using individual genome sequences. The method and the system of the present invention can predict the individual side effects or danger of a certain drug by analyzing the sequence of the exon region of a gene encoding various proteins involved in the pharmacokinetics or pharmacodynamics of a predetermined drug or drug group, and have high reliability and are widely applicable and universal.

1 . A method for personalizing selection of a drug for a subject using individual genome sequence variations of the subject, comprising:
 obtaining, by a computer system, information regarding gene sequences of the subject for a set of genes involved in pharmacodynamics or pharmacokinetics of a drug group, wherein the drug group consists of a plurality of drugs;   determining, by the computer system, gene sequence variation information indicating variations present in the gene sequences involved in the pharmacodynamics or pharmacokinetics of the group;   for each gene of the set of genes:
 determining, by the computer system, a gene sequence variation score; 
   for each protein encoded by a gene of the set of genes:
 calculating, by the computer system, an individual protein damage score for the protein by using [Equation 2], wherein [Equation 2] is: 
   
       
         
           
             
               
                 
                   S 
                   g 
                 
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                   ( 
                   
                     
                       v 
                       1 
                     
                     , 
                     … 
                     ⁢ 
                     
                         
                     
                     , 
                     
                       v 
                       n 
                     
                   
                   ) 
                 
               
               = 
               
                 
                   ( 
                   
                     
                       ∏ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       v 
                       i 
                       
                         w 
                         i 
                       
                     
                   
                   ) 
                 
                 
                   1 
                   / 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
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                       w 
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           wherein Sg is the individual protein damage score of a protein encoded by a gene g, n is the number of target sequence variations for analysis among sequence variations of the gene g, v i  is a gene sequence variation score of an i th  gene sequence variation, and w i  is a weighting assigned to the gene sequence variation score v i  of the i th  gene sequence variation; 
         
         for each drug in the drug group:
 calculating, by the computer system, an individual drug score by using [Equation 4], wherein [Equation 4] is: 
 
       
       
         
           
             
               
                 
                   S 
                   d 
                 
                 ⁡ 
                 
                   ( 
                   
                     
                       g 
                       1 
                     
                     , 
                     … 
                     ⁢ 
                     
                         
                     
                     , 
                     
                       g 
                       n 
                     
                   
                   ) 
                 
               
               = 
               
                 
                   ( 
                   
                     
                       ∏ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       g 
                       i 
                       
                         w 
                         i 
                       
                     
                   
                   ) 
                 
                 
                   1 
                   / 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
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                       w 
                       i 
                     
                   
                 
               
             
           
         
         
           wherein S d  is the individual drug score of a drug d, n is a number of proteins encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d, g i  is a protein damage score of a protein encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d, and w i  is a weighting assigned to the protein damage score g i  of the protein encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d; 
         
         ranking, by the computer system, drugs in the drug group by comparing the individual drug scores for the drugs; and 
         selecting a drug based on the ranking. 
       
     
     
         2 . The method according to  claim 1 , wherein the plurality of drugs in the drug group have a same ATC code. 
     
     
         3 . The method according to  claim 1 ,
 wherein the gene sequence variation information means information about substitution, addition, or deletion of a base constituting an exon of a gene.   
     
     
         4 . The method according to  claim 3 ,
 wherein the substitution, addition, or deletion of the base results from structural abnormality including breakage, deletion, duplication, inversion, or translocation of a chromosome.   
     
     
         5 . The method according to  claim 1 ,
 wherein the gene sequence variation score is calculated by applying one or more algorithms selected from the group consisting of SIFT (Sorting Intolerant From Tolerant), PolyPhen (Polymorphism Phenotyping), PolyPhen-2, MAPP (Multivariate Analysis of Protein Polymorphism), Logre (Log R Pfam E-value), MutationAssessor, MutationTaster, MutationTaster2, PROVEAN (Protein Variation Effect Analyzer), PMut, Condel, GERP (Genomic Evolutionary Rate Profiling), GERP++, CEO (Combinatorial Entropy Optimization), SNPeffect, fathmm, and CADD (Combined Annotation-Dependent Depletion) to a gene sequence variation.   
     
     
         6 . The method according to  claim 1 ,
 wherein the weighting assigned to the gene sequence variation score or the weighting assigned to the protein damage score is determined considering a class of the protein, pharmacodynamic or pharmacokinetic classification of the protein, pharmacokinetic parameters of the enzyme protein of a corresponding drug, a population group, or a race distribution.   
     
     
         7 . The method according to  claim 1 , further comprising:
 wherein the ranking step further comprises determining an order of priorities among drugs applicable to the subject by using the individual drug score; or wherein the selecting step further comprises determining whether or not to use the drugs applicable to the subject by using the individual drug score.   
     
     
         8 . The method according to  claim 1 ,
 wherein the drug group is information input by a user, information input from a prescription, or information input from a database including information about a drug effective in treating a predetermined disease.   
     
     
         9 . The method according to  claim 1 ,
 wherein the gene sequence variation information is acquired by a comparison analysis with a genome sequence of a reference group.   
     
     
         10 . The method according to  claim 1 , further comprising:
 calculating a prescription score.   
     
     
         11 . The method according to  claim 10 ,
 wherein if two or more drugs are determined on the basis of an order of priority among drugs and need to be administered at the same time, the prescription score is calculated by summarizing drug scores determined with respect to the respective drugs.   
     
     
         12 . The method according to  claim 1 , further comprising:
 providing one or more information selected from the group consisting of gene sequence variation information, a protein damage score, a drug score, and information used for calculation thereof.   
     
     
         13 . The method according to  claim 1 ,
 wherein the method is performed to prevent drug side effects.   
     
     
         14 . A computer-readable storage medium comprising stored instructions, wherein the instructions when executed by a processor cause the processor to perform steps comprising:
 obtaining information regarding gene sequences of a subject for a set of genes involved in pharmacodynamics or pharmacokinetics of a drug group, wherein the drug group consists of a plurality of drugs;   determining gene sequence variation information indicating variations present in the gene sequences involved in the pharmacodynamics or pharmacokinetics of the drug group;   for each gene of the set of genes:
 determining, by the computer system, a gene sequence variation score; 
   for each protein encoded by a gene of the set of genes
 calculating an individual protein damage score for the protein by using [Equation 2], wherein [Equation 2] is: 
   
       
         
           
             
               
                 
                   S 
                   g 
                 
                 ⁡ 
                 
                   ( 
                   
                     
                       v 
                       1 
                     
                     , 
                     … 
                     ⁢ 
                     
                         
                     
                     , 
                     
                       v 
                       n 
                     
                   
                   ) 
                 
               
               = 
               
                 
                   ( 
                   
                     
                       ∏ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       v 
                       i 
                       
                         w 
                         i 
                       
                     
                   
                   ) 
                 
                 
                   1 
                   / 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       w 
                       i 
                     
                   
                 
               
             
           
         
         
           wherein Sg is the individual protein damage score of a protein encoded by a gene g, n is the number of target sequence variations for analysis among sequence variations of the gene g, v i  is a gene sequence variation score of an i th  gene sequence variation, and w i  is a weighting assigned to the gene sequence variation score v i  of the i th  gene sequence variation; 
         
         for each drug in the drug group:
 calculating an individual drug score by using [Equation 4], wherein [Equation 4] is: 
 
       
       
         
           
             
               
                 
                   S 
                   d 
                 
                 ⁡ 
                 
                   ( 
                   
                     
                       g 
                       1 
                     
                     , 
                     … 
                     ⁢ 
                     
                         
                     
                     , 
                     
                       g 
                       n 
                     
                   
                   ) 
                 
               
               = 
               
                 
                   ( 
                   
                     
                       ∏ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       g 
                       i 
                       
                         w 
                         i 
                       
                     
                   
                   ) 
                 
                 
                   1 
                   / 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       w 
                       i 
                     
                   
                 
               
             
           
         
         
           wherein S d  is the individual drug score of a drug d, n is a number of proteins encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d, g i  is a protein damage score of a protein encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d, and w i  is a weighting assigned to the protein damage score g i  of the protein encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d; 
         
         ranking drugs in the drug group by comparing the individual drug scores for the drugs; and 
         selecting a drug based on the ranking. 
       
     
     
         15 . The computer-readable storage medium of  claim 14 , wherein the plurality of drugs in the drug group have a same ATC code. 
     
     
         16 . A system for providing information for personalizing drug selection using individual genome sequence variations, the system comprising:
 a processor;   a computer readable storage medium comprising stored instructions, wherein the instructions when executed by a processor cause the processor to perform steps comprising:   obtaining information regarding gene sequences of a subject for a set of genes involved in pharmacodynamics or pharmacokinetics of a drug group, wherein the drug group consists of a plurality of drugs;   determining gene sequence variation information indicating variations present in the gene sequences involved in the pharmacodynamics or pharmacokinetics of the drug group;   for each gene of the set of genes:
 determining, by the computer system, a gene sequence variation score; 
   for each protein encoded by a gene of the set of genes
 calculating an individual protein damage score for the protein by using [Equation 2], wherein [Equation 2] is: 
   
       
         
           
             
               
                 
                   S 
                   g 
                 
                 ⁡ 
                 
                   ( 
                   
                     
                       v 
                       1 
                     
                     , 
                     … 
                     ⁢ 
                     
                         
                     
                     , 
                     
                       v 
                       n 
                     
                   
                   ) 
                 
               
               = 
               
                 
                   ( 
                   
                     
                       ∏ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       v 
                       i 
                       
                         w 
                         i 
                       
                     
                   
                   ) 
                 
                 
                   1 
                   / 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       w 
                       i 
                     
                   
                 
               
             
           
         
         
           wherein Sg is the individual protein damage score of a protein encoded by a gene g, n is the number of target sequence variations for analysis among sequence variations of the gene g, v i  is a gene sequence variation score of an i th  gene sequence variation, and w i  is a weighting assigned to the gene sequence variation score v i  of the i th  gene sequence variation; 
         
         for each drug in the drug group:
 calculating an individual drug score by using [Equation 4], wherein [Equation 4] is: 
 
       
       
         
           
             
               
                 
                   S 
                   d 
                 
                 ⁡ 
                 
                   ( 
                   
                     
                       g 
                       1 
                     
                     , 
                     … 
                     ⁢ 
                     
                         
                     
                     , 
                     
                       g 
                       n 
                     
                   
                   ) 
                 
               
               = 
               
                 
                   ( 
                   
                     
                       ∏ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       g 
                       i 
                       
                         w 
                         i 
                       
                     
                   
                   ) 
                 
                 
                   1 
                   / 
                   
                     
                       ∑ 
                       
                         i 
                         = 
                         1 
                       
                       n 
                     
                     ⁢ 
                     
                         
                     
                     ⁢ 
                     
                       w 
                       i 
                     
                   
                 
               
             
           
         
         
           wherein S d  is the individual drug score of a drug d, n is a number of proteins encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d, g i  is a protein damage score of a protein encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d, and w i  is a weighting assigned to the protein damage score g i  of the protein encoded by one or more genes involved in the pharmacodynamics or pharmacokinetics of the drug group d; 
         
         ranking drugs in the drug group by comparing the individual drug scores for the drugs; and 
         selecting a drug based on the ranking. 
       
     
     
         17 . The system for providing information for personalizing drug selection using individual genome sequence variations of  claim 16 , wherein the plurality of drugs in the drug group have a same ATC code 
     
     
         18 . The system for providing information for personalizing drug selection using individual genome sequence variations of  claim 16 , wherein the instructions when executed by the processor cause the processor to further perform steps comprising calculating a prescription score by summarizing drug scores determined with respect to respective drugs if two or more drugs are determined on the basis of an order of priority among drugs and need to be administered at the same time. 
     
     
         19 . The system for providing information for personalizing drug selection using individual genome sequence variations of  claim 16 , further comprising:
 a user interface configured to provide drug scores of drugs or drug groups when a list of the drug groups is inputted by a user.   
     
     
         20 . The system for providing information for personalizing drug selection using individual genome sequence variations of  claim 16 , further comprising:
 a display unit configured to display the protein damage or the drug score, or to display a calculation process, or information as a ground for the calculation.   
     
     
         21 . The system for providing information for personalizing drug selection using individual genome sequence variations of  claim 16 , wherein the gene sequence variation information, protein damage score, drug score and information as a ground for the calculation are stored in the computer-readable storage medium and are updated when the database is updated.