| With the progress of sequencing technology,pharmacogenomics is playing a growing important role in exploring the personalized medication difference.Focusing on the pharmacogenomics,we need to think about how to reduce the drug side effects while increasing efficacy.Single nucleotide polymorphisms(SNPs)affect a patient’s response to drugs.Here we assessed the genetic predisposition to severe adverse drug reactions(SADRs)in different race/ethnic groups using the whole genome sequencing data from the gnomAD project.From 5 popular databases and Wang’s paper,we collected a total of 5,588 variant-to-drug associations containing 2,950 genetic variants within 356 genes that affect the 383 drugs.Among them,575 severe adverse events containing 372 genetic variants located in 79 genes have been annotated to be associated with 103 drugs.Nearly 90% of the SNPs associated with SADRs have maximum minor allele frequencies(MAFs)smaller than 1‰ among all races according to gnomAD.The genetic predisposition to SADRs varies from population to population,and from person to person,underscoring the significance of personalized drug prescription.Combinatorial drug can improve the therapeutic effect of the disease and reduce the dosage.At present,a widespread problem in pharmacology is to predict effective combination of drugs for improving the effectiveness of clinical practice.In order to achieve the goal of drug combination,we used the characteristics of drug properties and the biomolecular network to construct the prediction model.Evaluation results demonstrated that our model has better performance than the previous prediction methods.The AUC in test dataset is 0.84 and the model has good robustness and wide applicability.By integrating the above work,we developed a WEB-based platform for the personalized combination drug: PDCP(http://www.megabionet.org/pdcp/).PDCP can analyze the drug targets according to the CNV and mutation data submitted by user and return the possible combination of drugs.Our system provides useful resource in combinatorial drugs for both basis researches and clinical applications. |
