A fully phased accurate assembly of an individual human genome [article]

David Porubsky, Peter Ebert, Peter A. Audano, Mitchell R. Vollger, William T. Harvey, Katherine M. Munson, Melanie Sorensen, Arvis Sulovari, Marina Haukness, Maryam Ghareghani, Peter M. Lansdorp, Benedict Paten (+8 others)
2019 biorxiv/medrxiv   pre-print
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
more » ... 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.
doi:10.1101/855049 fatcat:rviihmslgjatvlbxtgqkmyqvxa