The Use of Next-Generation Sequencing in Pharmacogenomics.

Abstract

Next-generation sequencing (NGS) methods have become more commonly performed in clinical and research laboratories. This review summarizes the current laboratory NGS-based diagnostic approaches in pharmacogenomics including targeted multi-gene panel sequencing, whole-exome sequencing (WES), and whole-genome sequencing (WGS). Clinical laboratories perform multiple non-uniform types of pharmacogenetic panels, which can reduce the overall number of single-gene tests to be more cost-efficient. Compared to the targeted multi-gene panels, which are not typically designed to detect novel variants, WES and WGS have a greater potential to identify secondary pharmacogenomic findings, which might be predictive for the pharmacotherapy outcome of different patient settings. WGS overcomes the limitations of WES enabling a more accurate exome-sequencing at appropriate coverage and the sequencing of non-coding regions. Different NGS-based study designs with different test strategies and study populations, varying sample sizes, and distinct analytical and interpretation procedures lead to different identification results of pharmacogenomic variants. The rapid progress in gene sequencing technologies will overcome the clinical and laboratory challenges of WES and WGS. Further high throughput NGS-based pharmacogenomics studies in different populations and patient settings are necessary to expand knowledge about rare functional variants and to enhance translation in clinical practice.