Dense and accurate whole-chromosome haplotyping of individual genomes

Research output: Contribution to journalJournal articleResearchpeer-review


  • David Porubsky
  • Garg, Shilpa
  • Ashley D. Sanders
  • Jan O. Korbel
  • Victor Guryev
  • Peter M. Lansdorp
  • Tobias Marschall

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.

Original languageEnglish
Article number1293
JournalNature Communications
Number of pages10
Publication statusPublished - 2017
Externally publishedYes

    Research areas

  • Alleles, Chromosomes, Human/genetics, Diploidy, Gene Library, Genetic Variation, Genome, Human, Genomics/methods, Haplotypes, High-Throughput Nucleotide Sequencing/methods, Humans, Sequence Analysis, DNA/methods

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