Chromosome-scale, haplotype-resolved assembly of human genomes

Research output: Contribution to journalJournal articleResearchpeer-review


  • 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

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.

Original languageEnglish
JournalNature Biotechnology
Number of pages7
Publication statusE-pub ahead of print - 7 Dec 2020
Externally publishedYes

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