Chromosome-scale, haplotype-resolved assembly of human genomes.

TitleChromosome-scale, haplotype-resolved assembly of human genomes.
Publication TypeJournal Article
Year of Publication2021
AuthorsGarg, S, Fungtammasan, A, Carroll, A, Chou, M, Schmitt, A, Zhou, X, Mac, S, Peluso, P, Hatas, E, Ghurye, J, Maguire, J, Mahmoud, M, Cheng, H, Heller, D, Zook, JM, Moemke, T, Marschall, T, Sedlazeck, FJ, Aach, J, Chin, C-S, Church, GM, Li, H
JournalNat Biotechnol
Date Published2021 03

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.

Alternate JournalNat Biotechnol
PubMed ID33288905
PubMed Central IDPMC7954703
Grant ListR01 HG010040 / HG / NHGRI NIH HHS / United States
RM1 HG008525 / HG / NHGRI NIH HHS / United States
U01 HG010971 / HG / NHGRI NIH HHS / United States
K99 HG010906 / HG / NHGRI NIH HHS / United States
UM1 HG008898 / HG / NHGRI NIH HHS / United States