Clin Lab. 2023 Aug 1;69(8). doi: 10.7754/Clin.Lab.2023.230103.
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.
下一代测序（NGS）方法在临床和研究实验室中越来越普遍。
本文综述了当前临床 NGS 基于药物基因组学的诊断方法，包括靶向多基因panel 测序、全外显子组测序（WES）和全基因组测序（WGS）。
临床实验室进行多种非统一类型的药物基因组学panel，这可以降低整体单基因测试数量，从而提高成本效益。与通常不设计用于检测新变体的靶向多基因panel 相比，WES 和 WGS 更有可能发现次要的药物基因组学发现，这些发现可能对不同患者环境的药物治疗结果具有预测性。WGS 克服了 WES 的局限性，能够以适当的覆盖度更准确地进行外显子测序，并对非编码区域进行测序。不同的基于 NGS 的研究设计具有不同的测试策略和研究人群、不同的样本量以及不同的分析和解释程序，导致药物基因组学变异的识别结果不同。
基因测序技术的快速进步将克服 WES 和 WGS 的临床和实验室挑战。在不同人群和患者环境中进行更多高通量基于 NGS 的药物基因组学研究，对于扩展对稀有功能变体的认识并增强临床实践中的转化是必要的。
