Automated assembly of high-quality diploid human reference genomes

Author:

Jarvis Erich D.ORCID,Formenti GiulioORCID,Rhie ArangORCID,Guarracino AndreaORCID,Yang Chentao,Wood Jonathan,Tracey Alan,Thibaud-Nissen Francoise,Vollger Mitchell R.ORCID,Porubsky David,Cheng Haoyu,Asri Mobin,Logsdon Glennis A.,Carnevali Paolo,Chaisson Mark J.P.,Chin Chen-Shan,Cody Sarah,Collins JoannaORCID,Ebert PeterORCID,Escalona MerlyORCID,Fedrigo OlivierORCID,Fulton Robert S.,Fulton Lucinda L.,Garg Shilpa,Ghurye Jay,Granat Ana,Green EdwardORCID,Hall Ira,Harvey William,Hasenfeld Patrick,Hastie Alex,Haukness Marina,Jaeger Erich B.,Jain Miten,Kirsche MelanieORCID,Kolmogorov Mikhail,Korbel Jan O.,Koren Sergey,Korlach Jonas,Lee Joyce,Li DaofengORCID,Lindsay Tina,Lucas Julian,Luo Feng,Marschall Tobias,McDaniel Jennifer,Nie Fan,Olsen Hugh E.,Olson Nathan D.,Pesout TrevorORCID,Puiu Daniela,Regier Allison,Ruan Jue,Salzberg Steven L.,Sanders Ashley D.,Schatz Michael C.,Schmitt Anthony,Schneider Valerie A.,Selvaraj Siddarth,Shafin KishwarORCID,Shumate Alaina,Stober Catherine,Torrance James,Wagner Justin,Wang Jianxin,Wenger Aaron,Xiao Chuanle,Zimin Aleksey V.,Zhang Guojie,Wang Ting,Li HengORCID,Garrison ErikORCID,Haussler David,Zook Justin M.ORCID,Eichler Evan E.ORCID,Phillippy Adam M.,Paten Benedict,Howe KerstinORCID,Miga Karen H.,

Abstract

AbstractThe current human reference genome, GRCh38, represents over 20 years of effort to generate a high-quality assembly, which has greatly benefited society1, 2. However, it still has many gaps and errors, and does not represent a biological human genome since it is a blend of multiple individuals3, 4. Recently, a high-quality telomere-to-telomere reference genome, CHM13, was generated with the latest long-read technologies, but it was derived from a hydatidiform mole cell line with a duplicate genome, and is thus nearly homozygous5. To address these limitations, the Human Pangenome Reference Consortium (HPRC) recently formed with the goal of creating a collection of high-quality, cost-effective, diploid genome assemblies for a pangenome reference that represents human genetic diversity6. Here, in our first scientific report, we determined which combination of current genome sequencing and automated assembly approaches yields the most complete, accurate, and cost-effective diploid genome assemblies with minimal manual curation. Approaches that used highly accurate long reads and parent-child data to sort haplotypes during assembly outperformed those that did not. Developing a combination of all the top performing methods, we generated our first high- quality diploid reference assembly, containing only ∼4 gaps (range 0-12) per chromosome, most within + 1% of CHM13’s length. Nearly 1/4th of protein coding genes have synonymous amino acid changes between haplotypes, and centromeric regions showed the highest density of variation. Our findings serve as a foundation for assembling near-complete diploid human genomes at the scale required for constructing a human pangenome reference that captures all genetic variation from single nucleotides to large structural rearrangements.

Publisher

Cold Spring Harbor Laboratory

Cited by 17 articles. 订阅此论文施引文献 订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3