RT Journal Article
SR Electronic
T1 A fully phased accurate assembly of an individual human genome
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 855049
DO 10.1101/855049
A1 David Porubsky
A1 Peter Ebert
A1 Peter A. Audano
A1 Mitchell R. Vollger
A1 William T. Harvey
A1 Katherine M. Munson
A1 Melanie Sorensen
A1 Arvis Sulovari
A1 Marina Haukness
A1 Maryam Ghareghani
A1 Human Genome Structural Variation Consortium
A1 Peter M. Lansdorp
A1 Benedict Paten
A1 Scott E. Devine
A1 Ashley D. Sanders
A1 Charles Lee
A1 Mark J.P. Chaisson
A1 Jan O. Korbel
A1 Evan E. Eichler
A1 Tobias Marschall
YR 2019
UL http://biorxiv.org/content/early/2019/11/26/855049.abstract
AB The prevailing genome assembly paradigm is to produce consensus sequences that “collapse” parental haplotypes into a consensus sequence. Here, we leverage the chromosome-wide phasing and scaffolding capabilities of single-cell strand sequencing (Strand-seq)1,2 and combine them with high-fidelity (HiFi) long sequencing reads3, in a novel reference-free workflow for diploid de novo genome assembly. Employing this strategy, we produce completely phased de novo genome assemblies separately for each haplotype of a single individual of Puerto Rican origin (HG00733) in the absence of parental data. The assemblies are accurate (QV > 40), highly contiguous (contig N50 > 25 Mbp) with low switch error rates (0.4%) providing fully phased single-nucleotide variants (SNVs), indels, and structural variants (SVs). A comparison of Oxford Nanopore and PacBio phased assemblies identifies 150 regions that are preferential sites of contig breaks irrespective of sequencing technology or phasing algorithms.