title: HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies.
abstract: 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.
authors.affiliation: Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California 92053, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Edge
authors.affiliation: Department of Computer Science & Engineering, University of California, San Diego, La Jolla, California 92053, USA.
authors.forename: Vineet
authors.initials: V
authors.lastname: Bafna
authors.affiliation: Department of Pediatrics, School of Medicine, University of California, San Diego, La Jolla, California 92053, USA.
authors.forename: Vikas
authors.initials: V
authors.lastname: Bansal
mesh_terms: D020451:Contig Mapping / Q000379:methods* / Q000592:standards; D015894:Genome, Human; D023281:Genomics / Q000379:methods* / Q000592:standards; D006239:Haplotypes; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods* / Q000592:standards; D012984:Software