TY  - JOUR
A1  - Edge, Peter
A1  - Bafna, Vineet
A1  - Bansal, Vikas
T1  - HapCUT2: robust and accurate haplotype assembly for diverse sequencing technologies
Y1  - 2016/12/09 
JF  - Genome Research 
JO  - Genome Research 
DO  - 10.1101/gr.213462.116 
SP  - gr.213462.116 
UR  - http://genome.cshlp.org/content/early/2016/12/09/gr.213462.116.abstract 
N2  - 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 datasets 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 90x coverage whole-genome Hi-C dataset  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. 
ER  -