Dense and accurate whole-chromosome haplotyping of individual genomes.

Abstract:

:The diploid nature of the human genome is neglected in many analyses done today, where a genome is perceived as a set of unphased variants with respect to a reference genome. This lack of haplotype-level analyses can be explained by a lack of methods that can produce dense and accurate chromosome-length haplotypes at reasonable costs. Here we introduce an integrative phasing strategy that combines global, but sparse haplotypes obtained from strand-specific single-cell sequencing (Strand-seq) with dense, yet local, haplotype information available through long-read or linked-read sequencing. We provide comprehensive guidance on the required sequencing depths and reliably assign more than 95% of alleles (NA12878) to their parental haplotypes using as few as 10 Strand-seq libraries in combination with 10-fold coverage PacBio data or, alternatively, 10X Genomics linked-read sequencing data. We conclude that the combination of Strand-seq with different technologies represents an attractive solution to chart the genetic variation of diploid genomes.

journal_name

Nat Commun

journal_title

Nature communications

authors

Porubsky D,Garg S,Sanders AD,Korbel JO,Guryev V,Lansdorp PM,Marschall T

doi

10.1038/s41467-017-01389-4

subject

Has Abstract

pub_date

2017-11-03 00:00:00

pages

1293

issue

1

issn

2041-1723

pii

10.1038/s41467-017-01389-4

journal_volume

8

pub_type

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