News & Publications

Dense and accurate whole-chromosome haplotyping of individual genomes

Posted November 7, 2017 | Publications

Porubsky D, Garg S, Sanders AD, Korbel JO, Guryev V, Lansdorp PM & Marschall T. Dense and accurate whole-chromosome haplotyping of individual genomes.  Nat Commun 8: 1293 2017.


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.

PMID 29101320