Haplotype-resolved de novo assembly using phased assembly graphs with hifiasm

Nat Methods. 2021 Feb;18(2):170-175. doi: 10.1038/s41592-020-01056-5. Epub 2021 Feb 1.

Abstract

Haplotype-resolved de novo assembly is the ultimate solution to the study of sequence variations in a genome. However, existing algorithms either collapse heterozygous alleles into one consensus copy or fail to cleanly separate the haplotypes to produce high-quality phased assemblies. Here we describe hifiasm, a de novo assembler that takes advantage of long high-fidelity sequence reads to faithfully represent the haplotype information in a phased assembly graph. Unlike other graph-based assemblers that only aim to maintain the contiguity of one haplotype, hifiasm strives to preserve the contiguity of all haplotypes. This feature enables the development of a graph trio binning algorithm that greatly advances over standard trio binning. On three human and five nonhuman datasets, including California redwood with a ~30-Gb hexaploid genome, we show that hifiasm frequently delivers better assemblies than existing tools and consistently outperforms others on haplotype-resolved assembly.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Algorithms
  • Genome*
  • Haplotypes*
  • Sequence Analysis, DNA / methods*