Abstract
We present Virtual Pharmacist, a web-based platform that takes common types of high-throughput data, namely microarray SNP genotyping data, FASTQ and Variant Call Format (VCF) files as inputs, and reports potential drug responses in terms of efficacy, dosage and toxicity at one glance. Batch submission facilitates multivariate analysis or data mining of targeted groups. Individual analysis consists of a report that is readily comprehensible to patients and practioners who have basic knowledge in pharmacology, a table that summarizes variants and potential affected drug response according to the US Food and Drug Administration pharmacogenomic biomarker labeled drug list and PharmGKB, and visualization of a gene-drug-target network. Group analysis provides the distribution of the variants and potential affected drug response of a target group, a sample-gene variant count table, and a sample-drug count table. Our analysis of genomes from the 1000 Genome Project underlines the potentially differential drug responses among different human populations. Even within the same population, the findings from Watson’s genome highlight the importance of personalized medicine. Virtual Pharmacist can be accessed freely at http://www.sustc-genome.org.cn/vp or installed as a local web server. The codes and documentation are available at the GitHub repository (https://github.com/VirtualPharmacist/vp). Administrators can download the source codes to customize access settings for further development.
Highlights
Since the first release of the human genome in 2000, there has been continuing interest to understand genetic variants among individuals
To meet the need for high-quality genotypic and phenotypic information, the National Institute of Health initiated the Pharmacogenetics Research Network [5], which led to the development of the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), a curated resource that contains the relationships between drugs, diseases/ phenotypes, and genes involved in pharmacokinetics and pharmacodynamics [6]
We present Virtual Pharmacist (VP), a secure online platform that can be used to interpret the potential impact of individual genetic variations on drug response, based on the high-quality resources from PharmGKB [6], dbSNP [1], and The DrugBank database [22], which is a comprehensive resource that curates knowledge about drugs and their targets
Summary
Since the first release of the human genome in 2000, there has been continuing interest to understand genetic variants among individuals. Genetic variations can affect drug responses involving efficacy and safety to different extents, and the outcomes affect drug development, prescription, and patient care [2]. The effective dosage of the drug warfarin is strongly affected by genetic variants of the P450 cytochrome CYP2C9 and the vitamin K. To meet the need for high-quality genotypic and phenotypic information, the National Institute of Health initiated the Pharmacogenetics Research Network [5], which led to the development of the Pharmacogenetics and Pharmacogenomics Knowledge Base (PharmGKB), a curated resource that contains the relationships between drugs, diseases/ phenotypes, and genes involved in pharmacokinetics and pharmacodynamics [6]. In 2010, the US Food and Drug Administration (FDA) issued a black-box warning of diminished clopidogrel effectiveness in poor metabolizers and suggested testing for the CYP2C19 genotype
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