HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies

By Peter Edge, Vineet Bafna, Vikas Bansal. Genome Research, 2017

331 citations recorded by the source corpus.

Many tools have been developed for haplotype assembly—the reconstruction of individual haplotypes using reads mapped to a reference genome sequence. Due to increasing interest in obtaining haplotype-resolved human genomes, a range of new sequencing protocols and technologies have been developed to enable the reconstruction of whole-genome haplotypes. However, existing computational methods designed to handle specific technologies do not scale well on data from different protocols. We describe a new algorithm, HapCUT2, that extends our previous method (HapCUT) to handle multiple sequencing technologies. Using simulations and whole-genome sequencing (WGS) data from multiple different data types—dilution pool sequencing, linked-read sequencing, single molecule real-time (SMRT) sequencing, and proximity ligation (Hi-C) sequencing—we show that HapCUT2 rapidly assembles haplotypes with best-in-class accuracy for all data types. In particular, HapCUT2 scales well for high sequencing coverage and rapidly assembled haplotypes for two long-read WGS data sets on which other methods struggled. Further, HapCUT2 directly models Hi-C specific error modalities, resulting in significant improvements in error rates compared to HapCUT, the only other method that could assemble haplotypes from Hi-C data. Using HapCUT2, haplotype assembly from a 90× coverage whole-genome Hi-C data set yielded high-resolution haplotypes (78.6% of variants phased in a single block) with high pairwise phasing accuracy (∼98% across chromosomes). Our results demonstrate that HapCUT2 is a robust tool for haplotype assembly applicable to data from diverse sequencing technologies.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/1cc74dc973f837fc6a599c9cba64d694e99939e1

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In Molecular Biology

Citations in the corpus

Piercing the dark matter: bioinformatics of long-range sequencing and mapping (2018, methodology): “Consequently, these libraries have a remarkable capability for phasing and scaffolding , allowing for nearly entire eukaryotic chromosomes to be resolved from end to end when combined with a high-quality draft assembly 13 .”
De novo assembly of haplotype-resolved genomes with trio binning (2018, unknown): “15 and 16), suggesting artefactual duplications in the UMD3.”