| Literature DB >> 33288905 |
Shilpa Garg1,2,3, Arkarachai Fungtammasan4, Andrew Carroll5, Mike Chou6, Anthony Schmitt7, Xiang Zhou7, Stephen Mac7, Paul Peluso8, Emily Hatas8, Jay Ghurye9, Jared Maguire9, Medhat Mahmoud10, Haoyu Cheng11,12, David Heller13, Justin M Zook14, Tobias Moemke15, Tobias Marschall15,16, Fritz J Sedlazeck10, John Aach6, Chen-Shan Chin17, George M Church18, Heng Li19,20.
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 1 day. 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 25 Mb 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.Entities:
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Year: 2020 PMID： 33288905 PMCID： PMC7954703 DOI： 10.1038/s41587-020-0711-0
Source DB: PubMed Journal: Nat Biotechnol ISSN： 1087-0156 Impact factor: 54.908