Method and system for selecting drug on basis of individual protein damage information for preventing side effects of drug

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 of predicting a functional deficiency of a protein based on individual genome sequence information of a subject, comprising the steps of:
 determining, by an evaluation system, gene sequence variation information of a gene encoding the protein by using individual genome sequence information;   calculating, by the evaluation system, an individual protein damage score associated with the protein using the gene sequence variation information; and   predicting, by the evaluation system, the functional deficiency of the protein based on the individual protein damage score.   
     
     
         2 . The method of  claim 1 , wherein the gene sequence variation information comprises a gene sequence variation score calculated using 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). 
     
     
         3 . The method of  claim 2 , wherein gene sequence variation information comprises two or more gene sequence variation scores, and the protein damage score is calculated as a mean of the two or more gene sequence variation scores. 
     
     
         4 . The method of  claim 3 , wherein the mean is calculated by one or more selected from the group consisting of: a geometric mean, an arithmetic mean, a harmonic mean, an arithmetic geometric mean, an arithmetic harmonic mean, a geometric harmonic mean, Pythagorean means, a Heronian mean, a contraharmonic mean, a root mean square deviation, a centroid mean, an interquartile mean, a quadratic mean, a truncated mean, a Winsorized mean, a weighted mean, a weighted geometric mean, a weighted arithmetic mean, a weighted harmonic mean, a mean of a function, a generalized mean, a generalized f-mean, a percentile, a maximum value, a minimum value, a mode, a median, a mid-range, a central tendency, or by simple multiplication or weighted multiplication. 
     
     
         5 . The method of  claim 1 , wherein the gene sequence variation information is determined by a comparison analysis with a genome sequence of a reference group. 
     
     
         6 . The method of  claim 1 , wherein the individual protein damage score is calculated by the following Equation 1: 
       
         
           
             
               
                 
                   
                     
                       
                         S 
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                            
                           
                             v 
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                         ) 
                       
                     
                     = 
                     
                       
                         ( 
                         
                           
                             1 
                             n 
                           
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                               ∑ 
                               
                                 i 
                                 = 
                                 1 
                               
                               n 
                             
                              
                             
                               v 
                               i 
                               p 
                             
                           
                         
                         ) 
                       
                       
                         1 
                         p 
                       
                     
                   
                 
                 
                   
                     [ 
                     
                       Equation 
                        
                       
                           
                       
                        
                       1 
                     
                     ] 
                   
                 
               
             
           
         
         wherein in Equation 1, S g  is a 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 p is a real number other than 0. 
       
     
     
         7 . The method of  claim 1 , wherein the individual protein damage score is calculated by the following Equation 2: 
       
         
           
             
               
                 
                   
                     
                       
                         S 
                         g 
                       
                        
                       
                         ( 
                         
                           
                             v 
                             
                               
                                 1 
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                                 … 
                               
                                
                               
                                   
                               
                             
                           
                            
                           
                             v 
                             n 
                           
                         
                         ) 
                       
                     
                     = 
                     
                       
                         ( 
                         
                           
                             ∏ 
                             
                               i 
                               = 
                               1 
                             
                             n 
                           
                            
                           
                             v 
                             i 
                             
                               w 
                               i 
                             
                           
                         
                         ) 
                       
                       
                         1 
                         / 
                         
                           
                             ∑ 
                             
                               i 
                               = 
                               1 
                             
                             n 
                           
                            
                           
                             w 
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                     [ 
                     
                       Equation 
                        
                       
                           
                       
                        
                       2 
                     
                     ] 
                   
                 
               
             
           
         
         wherein in Equation 2, S g  is a 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. 
       
     
     
         8 . The method of  claim 1 , wherein the individual protein damage score is calculated by assigning a weighting determined considering a class of the protein, pharmacodynamics or pharmacokinetics of the protein, a population group of the subject, or a distribution of protein damage scores in the population. 
     
     
         9 . The method of  claim 1 , further comprising the step of: predicting, by the evaluation system, an effect of a drug on the subject based on the functional deficiency of the protein, wherein the protein is associated with pharmacodynamics or pharmacokinetics of the drug. 
     
     
         10 . The method of  claim 9 , the protein is a target, an enzyme, a carrier, or a transporter protein. 
     
     
         11 . The method of  claim 10 , wherein the drug is an inhibitor of the protein. 
     
     
         12 . The method of  claim 11 , wherein the drug is Rivaroxaban and the protein is Factor 10. 
     
     
         13 . The method of  claim 9 , wherein the effect of the drug to the subject comprises: a therapeutic effect, or a side effect to the subject. 
     
     
         14 . The method of  claim 1 , further comprising the step of: providing, by the evaluation system, one or more of the information selected from the group consisting of the gene sequence variation information, the gene sequence variation score, the individual protein damage score, and information used for calculation thereof. 
     
     
         15 . The method of  claim 14 , wherein the one or more of the information is provided on a user interface of a device of the subject or a doctor to prevent a side effect of the drug to the subject. 
     
     
         16 . A system for predicting a functional deficiency of a protein, comprising:
 a processor;   a communication unit configured to receive individual genome sequence information;   a computer readable medium storing modules executable by the processor, the modules comprising:
 a first calculation module configured to determine gene sequence variation information of a gene encoding the protein by using the individual genome sequence information, 
 a second calculation module configured to calculate an individual protein damage score associated with the protein by using the gene sequence variation information, the individual protein damage score providing for prediction of the functional deficiency of the protein based on the individual protein damage score; and 
 a display unit configured to display the individual protein damage score for the prediction of the functional deficiency of the protein. 
   
     
     
         17 . The system of  claim 16 , further comprising:
 a fourth calculation module configured to predict an effect of a drug on the subject based on the functional deficiency of the protein, wherein the protein is associated with pharmacodynamics or pharmacokinetics of the drug.   
     
     
         18 . A computer-readable medium comprising an execution module for executing a processor that performs an operation of predicting a functional deficiency of a protein, comprising the steps of:
 acquiring individual genome sequence information;   calculating gene sequence variation information of a gene encoding the protein by using the individual genome sequence information;   calculating an individual protein damage score associated with the protein by using the gene sequence variation information; and   predicting the functional deficiency of the protein based on the individual protein damage score.   
     
     
         19 . The computer-readable medium of  claim 18 , wherein the execution module further performs an operation of: predicting an effect of a drug to the subject based on the functional deficiency of the protein, wherein the protein is associated with pharmacodynamics or pharmacokinetics of the drug.