Haplotype-resolved de novo assembly with phased assembly graphs

TL;DR

Hifiasm is a new assembler that uses high-fidelity long reads to produce high-quality, haplotype-resolved genome assemblies, outperforming existing methods especially in complex genomes.

Contribution

The paper introduces hifiasm, a novel assembler that preserves all haplotypes in a phased assembly graph, enabling superior haplotype-resolved assemblies compared to prior algorithms.

Findings

Hifiasm outperforms existing tools on multiple datasets.

It effectively assembles complex genomes like redwood.

It advances trio binning with a new graph-based approach.

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 new 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 non-human datasets, including California redwood with a $\sim$30-gigabase hexaploid genome, we show that hifiasm frequently delivers better assemblies than existing tools and consistently outperforms others on haplotype-resolved assembly.