Background: Advancement of next-generation sequencing (NGS) technologies provides opportunities for large-scale Pharmacogenetic (PGx) studies and pre-emptive PGx testing to cover a wide range of genotypes present in diverse populations. However, NGS-based PGx testing is limited by the lack of comprehensive computational tools to support genetic data analysis and clinical decisions.
Methods: Bioinformatics utilities specialized for human genomics and the latest cloud-based technologies are used for developing a bioinformatics pipeline for analyzing the genomic sequence data and reporting PGx genotypes. A database was created and integrated in the pipeline for filtering the actionable PGx variants and clinical interpretations. Strict quality verification procedures were conducted on variant calls with whole genome sequencing (WGS) dataset of the 1000 Genomes Project (G1K). The accuracy of PGx allele identification was validated using the whole genome sequencing dataset of the Pharmacogenetics Reference Materials from the Centers for Disease Control and Prevention (CDC).
Results: The newly created bioinformatics pipeline, Pgxtools, can analyze genomic sequence data, identify actionable variants in 13 PGx relevant genes, and generate reports annotated with specific interpretations and recommendations based on clinical practice guidelines. Verified with two independent methods, we have found that Pgxtools consistently identifies variants more accurately than the results in the G1K dataset on GRCh37 and GRCh38.
Conclusions: Pgxtools provides an integrated workflow for large-scale genomic data analysis and PGx clinical decision support. Implemented with cloud-native technologies, it is highly portable in a wide variety of environments from a single laptop to high performance computing clusters and cloud platforms for different production scales and requirements.
