Best practices for variant calling in clinical sequencing.
Best practices for variant calling in clinical sequencing.
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DOI：
10.1186/s13073-020-00791-w
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发表时间：
2020-10-26
期刊：
影响因子：
12.3
通讯作者：
Koboldt DC
中科院分区：
文献类型：
--
作者：
Koboldt DC
下一代测序技术极大地扩展了针对遗传性疾病和癌症等疾病的临床基因检测。 NGS 数据中准确的变异调用是几乎所有下游分析和解释过程所依赖的关键步骤。正如 NGS 技术在过去 10 年中取得了长足的发展一样，用于检测临床样本中序列变异的软件工具和方法也取得了长足的发展。在这篇综述中，我讨论了临床测序研究中变异检出的当前最佳实践，特别强调遗传性疾病的三重奏测序和癌症患者的体细胞突变检测。我描述了用于变异检测的组合测序、外显子组测序和全基因组测序的相对优势和劣势。还提供了用于调用不同类别变体的推荐工具和策略，以及有关变体审查、验证和基准测试的指导，以确保最佳性能。尽管NGS技术在不断发展，新功能（例如长读长单分子测序）不断出现，但从长远来看，本次综述中的“最佳实践”原则应该与临床变异检出相关。
Next-generation sequencing technologies have enabled a dramatic expansion of clinical genetic testing both for inherited conditions and diseases such as cancer. Accurate variant calling in NGS data is a critical step upon which virtually all downstream analysis and interpretation processes rely. Just as NGS technologies have evolved considerably over the past 10 years, so too have the software tools and approaches for detecting sequence variants in clinical samples. In this review, I discuss the current best practices for variant calling in clinical sequencing studies, with a particular emphasis on trio sequencing for inherited disorders and somatic mutation detection in cancer patients. I describe the relative strengths and weaknesses of panel, exome, and whole-genome sequencing for variant detection. Recommended tools and strategies for calling variants of different classes are also provided, along with guidance on variant review, validation, and benchmarking to ensure optimal performance. Although NGS technologies are continually evolving, and new capabilities (such as long-read single-molecule sequencing) are emerging, the “best practice” principles in this review should be relevant to clinical variant calling in the long term.
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