Extended haplotype-phasing of long-read de novo genome assemblies using Hi-C.

Journal Article (Journal Article)

Haplotype-resolved genome assemblies are important for understanding how combinations of variants impact phenotypes. To date, these assemblies have been best created with complex protocols, such as cultured cells that contain a single-haplotype (haploid) genome, single cells where haplotypes are separated, or co-sequencing of parental genomes in a trio-based approach. These approaches are impractical in most situations. To address this issue, we present FALCON-Phase, a phasing tool that uses ultra-long-range Hi-C chromatin interaction data to extend phase blocks of partially-phased diploid assembles to chromosome or scaffold scale. FALCON-Phase uses the inherent phasing information in Hi-C reads, skipping variant calling, and reduces the computational complexity of phasing. Our method is validated on three benchmark datasets generated as part of the Vertebrate Genomes Project (VGP), including human, cow, and zebra finch, for which high-quality, fully haplotype-resolved assemblies are available using the trio-based approach. FALCON-Phase is accurate without having parental data and performance is better in samples with higher heterozygosity. For cow and zebra finch the accuracy is 97% compared to 80-91% for human. FALCON-Phase is applicable to any draft assembly that contains long primary contigs and phased associate contigs.

Full Text

Duke Authors

Cited Authors

  • Kronenberg, ZN; Rhie, A; Koren, S; Concepcion, GT; Peluso, P; Munson, KM; Porubsky, D; Kuhn, K; Mueller, KA; Low, WY; Hiendleder, S; Fedrigo, O; Liachko, I; Hall, RJ; Phillippy, AM; Eichler, EE; Williams, JL; Smith, TPL; Jarvis, ED; Sullivan, ST; Kingan, SB

Published Date

  • April 28, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 1935 -

PubMed ID

  • 33911078

Pubmed Central ID

  • PMC8081726

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-020-20536-y


  • eng

Conference Location

  • England