De novo assembly of haplotype-resolved genomes with trio binning

By Sergey Koren, Arang Rhie, Brian Walenz, A. Dilthey, Derek M. Bickhart, S. Kingan, S. Hiendleder, John L. Williams, T. Smith, Adam M. Phillippy. Nature Biotechnology, 2018

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Complex allelic variation hampers the assembly of haplotype-resolved sequences from diploid genomes. We developed trio binning, an approach that simplifies haplotype assembly by resolving allelic variation before assembly. In contrast with prior approaches, the effectiveness of our method improved with increasing heterozygosity. Trio binning uses short reads from two parental genomes to first partition long reads from an offspring into haplotype-specific sets. Each haplotype is then assembled independently, resulting in a complete diploid reconstruction. We used trio binning to recover both haplotypes of a diploid human genome and identified complex structural variants missed by alternative approaches. We sequenced an F1 cross between the cattle subspecies Bos taurus taurus and Bos taurus indicus and completely assembled both parental haplotypes with NG50 haplotig sizes of >20 Mb and 99.998% accuracy, surpassing the quality of current cattle reference genomes. We suggest that trio binning improves diploid genome assembly and will facilitate new studies of haplotype variation and inheritance.

Subfields: Genetics, Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/85ffbe183e29c9f1815fa91ce7df184f1df83f0c

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Citations in the corpus

Merqury: reference-free quality, completeness, and phasing assessment for genome assemblies (2020, methodology): “For a comparison of multiple assemblies, we demonstrate Merqury on haplotype-resolved (TrioCanu [10]), pseudo-haplotype (FALCON-Unzip [9]), and mixed-haplotype (Canu [33]) assemblies of this hybrid genome.”
Long-read human genome sequencing and its applications (2020, neutral): “…genome assembly is now becoming feasible with new strategies that take advantage of parental information to phase long reads (such as trio binning ) 87 , computational methods that take advantage of the inherent phasing present in long-read data (such as FALCON-Unzip) 75 and methods that apply…”
Accurate circular consensus long-read sequencing improves variant detection and assembly of a human genome (2019, methodology): “Short reads from the parents of HG002 were used to identify k -mers unique to one parent and then partition (trio bin) the CCS reads by haplotype 42 father (68.9% binned).”
HiCanu: accurate assembly of segmental duplications, satellites, and allelic variants from high-fidelity long reads (2020, methodology): “Only HiCanu and TrioCanu were able to recover all alleles with 100% sequence identity (Supplemental Tables S10,S11).”