美国贝勒医学院Fritz J. Sedlazeck等研究人员，合作完成跨串联重复序列的大小基因组变异分析和基准测试。该项研究成果于2024年4月26日在线发表在《自然—生物技术》杂志上。

研究人员表示，串联重复序列（TR）在人类基因组中具有高度多态性，有数千个相关的分子特征，并与60多种疾病表型相关。然而，由于在变异捕捉和展示方面存在挑战，以及缺乏全基因组标准，它们常常被排除在大规模研究之外。

为了促进TR方法的发展，研究人员创建了一个TR区域目录，并在86个单体型解析的人类长读数集合中探索了TR的特性。研究人员从“瓶中基因组”（Genome in a Bottle，GIAB）HG002个体中整理出变异，创建了一个TR数据集，用于对现有和未来的TR分析方法进行基准测试。

研究人员还提出了一种改进的变异比较方法，它能处理长度超过4bp的变异和不同等位基因的代表性。TR目录覆盖了基因组的8.1%，每个个体拥有约24.9%的变异，其中包括GIAB HG002“真相集”TR基准的124728个小型变异和17988个大型变异。研究人员展示了这一管线在短读数和长读数技术中的实用性。

附：英文原文

Title: Analysis and benchmarking of small and large genomic variants across tandem repeats

Author: English, Adam C., Dolzhenko, Egor, Ziaei Jam, Helyaneh, McKenzie, Sean K., Olson, Nathan D., De Coster, Wouter, Park, Jonghun, Gu, Bida, Wagner, Justin, Eberle, Michael A., Gymrek, Melissa, Chaisson, Mark J. P., Zook, Justin M., Sedlazeck, Fritz J.

Issue&Volume: 2024-04-26

Abstract: Tandem repeats (TRs) are highly polymorphic in the human genome, have thousands of associated molecular traits and are linked to over 60 disease phenotypes. However, they are often excluded from at-scale studies because of challenges with variant calling and representation, as well as a lack of a genome-wide standard. Here, to promote the development of TR methods, we created a catalog of TR regions and explored TR properties across 86 haplotype-resolved long-read human assemblies. We curated variants from the Genome in a Bottle (GIAB) HG002 individual to create a TR dataset to benchmark existing and future TR analysis methods. We also present an improved variant comparison method that handles variants greater than 4bp in length and varying allelic representation. The 8.1% of the genome covered by the TR catalog holds ~24.9% of variants per individual, including 124,728 small and 17,988 large variants for the GIAB HG002 ‘truth-set’ TR benchmark. We demonstrate the utility of this pipeline across short-read and long-read technologies.

DOI: 10.1038/s41587-024-02225-z

Source: https://www.nature.com/articles/s41587-024-02225-z