小柯机器人

美国哈佛医学院Heng Li等研究人员合作实现染色体尺度下、单体型分辨率的人类基因组装配。相关论文于2020年12月7日在线发表在《自然—生物技术》杂志上。

研究人员提出了一种称为二倍体组装（DipAsm）的方法，该方法对单个个体使用长而准确的读长和长距离构象数据，可在1天之内生成染色体规模的定相组装。DipAsm被应用于四个公共人类基因组，PGP1、HG002、NA12878和HG00733，DipAsm产生了单体型分辨的程序集，具有最小重叠群长度，可覆盖50％的已知基因组（NG50）直至25 Mb，并在大约90.5％的杂合位点达到定相98-99％的准确性，且在连续性和定相完整性方面均优于其他方法。

研究人员证明了染色体规模的定相装配对于发现结构变异（SV）的重要性，包括数千个新的转座子插入，以及高度多态性和医学上重要的区域，例如人白细胞抗原（HLA）和杀伤细胞免疫球蛋白样受体（KIR）区域。DipAsm将促进高质量的精准医疗以及个体单体型变异和种群多样性的研究。

据了解，单体型分辨或定相的基因组组装可提供基因组及其复杂遗传变异的完整图谱。但是，当前用于定相装配的算法要么无法生成染色体尺度的定相，要么需要谱系信息，这限制了它们的应用。

附：英文原文

Title: Chromosome-scale, haplotype-resolved assembly of human genomes

Author: Shilpa Garg, Arkarachai Fungtammasan, Andrew Carroll, Mike Chou, Anthony Schmitt, Xiang Zhou, Stephen Mac, Paul Peluso, Emily Hatas, Jay Ghurye, Jared Maguire, Medhat Mahmoud, Haoyu Cheng, David Heller, Justin M. Zook, Tobias Moemke, Tobias Marschall, Fritz J. Sedlazeck, John Aach, Chen-Shan Chin, George M. Church, Heng Li

Issue&Volume: 2020-12-07

Abstract: Haplotype-resolved or phased genome assembly provides a complete picture of genomes and their complex genetic variations. However, current algorithms for phased assembly either do not generate chromosome-scale phasing or require pedigree information, which limits their application. We present a method named diploid assembly (DipAsm) that uses long, accurate reads and long-range conformation data for single individuals to generate a chromosome-scale phased assembly within 1day. Applied to four public human genomes, PGP1, HG002, NA12878 and HG00733, DipAsm produced haplotype-resolved assemblies with minimum contig length needed to cover 50% of the known genome (NG50) up to 25Mb and phased ~99.5% of heterozygous sites at 98–99% accuracy, outperforming other approaches in terms of both contiguity and phasing completeness. We demonstrate the importance of chromosome-scale phased assemblies for the discovery of structural variants (SVs), including thousands of new transposon insertions, and of highly polymorphic and medically important regions such as the human leukocyte antigen (HLA) and killer cell immunoglobulin-like receptor (KIR) regions. DipAsm will facilitate high-quality precision medicine and studies of individual haplotype variation and population diversity.

DOI: 10.1038/s41587-020-0711-0

Source: https://www.nature.com/articles/s41587-020-0711-0

Nature Biotechnology：《自然—生物技术》，创刊于1996年。隶属于施普林格·自然出版集团，最新IF：68.164
官方网址：https://www.nature.com/nbt/
投稿链接：https://mts-nbt.nature.com/cgi-bin/main.plex