Applied and Translational Neurogenomics Group, VIB Center for Molecular Neurology, VIB, Antwerp, Belgium.
Applied and Translational Neurogenomics Group, Department of Biomedical Sciences, University of Antwerp, Antwerp, Belgium.
Nat Rev Genet. 2021 Sep;22(9):572-587. doi: 10.1038/s41576-021-00367-3. Epub 2021 May 28.
Long-read sequencing technologies have now reached a level of accuracy and yield that allows their application to variant detection at a scale of tens to thousands of samples. Concomitant with the development of new computational tools, the first population-scale studies involving long-read sequencing have emerged over the past 2 years and, given the continuous advancement of the field, many more are likely to follow. In this Review, we survey recent developments in population-scale long-read sequencing, highlight potential challenges of a scaled-up approach and provide guidance regarding experimental design. We provide an overview of current long-read sequencing platforms, variant calling methodologies and approaches for de novo assemblies and reference-based mapping approaches. Furthermore, we summarize strategies for variant validation, genotyping and predicting functional impact and emphasize challenges remaining in achieving long-read sequencing at a population scale.
长读测序技术现在已经达到了足够的准确性和产量水平，可用于对数千个样本进行变异检测。随着新的计算工具的发展，过去两年中已经出现了第一批涉及长读测序的人群规模研究，而且考虑到该领域的持续进步，可能会有更多的研究出现。在这篇综述中，我们调查了人群规模长读测序的最新进展，强调了规模化方法的潜在挑战，并就实验设计提供了指导。我们概述了当前的长读测序平台、变异调用方法以及从头组装和基于参考的映射方法。此外，我们总结了变异验证、基因分型和预测功能影响的策略，并强调了在人群规模上实现长读测序仍面临的挑战。
