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. 2016 Jun 15;32(12):i234-i242.
doi: 10.1093/bioinformatics/btw276.

Read-based phasing of related individuals

Shilpa Garg  1 , Marcel Martin  2 , Tobias Marschall  3
Affiliations

Read-based phasing of related individuals

Shilpa Garg et al. Bioinformatics. .

Abstract

Motivation: Read-based phasing deduces the haplotypes of an individual from sequencing reads that cover multiple variants, while genetic phasing takes only genotypes as input and applies the rules of Mendelian inheritance to infer haplotypes within a pedigree of individuals. Combining both into an approach that uses these two independent sources of information-reads and pedigree-has the potential to deliver results better than each individually.

Results: We provide a theoretical framework combining read-based phasing with genetic haplotyping, and describe a fixed-parameter algorithm and its implementation for finding an optimal solution. We show that leveraging reads of related individuals jointly in this way yields more phased variants and at a higher accuracy than when phased separately, both in simulated and real data. Coverages as low as 2× for each member of a trio yield haplotypes that are as accurate as when analyzed separately at 15× coverage per individual.

Availability and implementation: https://bitbucket.org/whatshap/whatshap

Contact: t.marschall@mpi-inf.mpg.de.

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Figures

Fig. 1.
Fig. 1.
Seven SNP loci covered by reads (horizontal bars) in three individuals. Unphased genotypes are indicated by labels 0/0, 0/1 and 1/1. The alleles that a read supports are printed in white
Fig. 2.
Fig. 2.
Simulated dataset (top) and real dataset (bottom): phasing error rate (x-axis) versus completeness in terms of the fraction of unphased SNPs (y-axis) for PedMEC-G-5 (solid line), wMEC-5 (dashed line) and wMEC-15 (dotted line). Average coverage (per individual) of input data is encoded by circles of different sizes
Fig. 3.
Fig. 3.
Three-way comparison of phasings provided by SHAPEIT, 10XGenomics and PedMEC-G-5 (on 15× coverage data). Of all pairs of consecutive SNPs phased by all three methods, the percentages of cases where the phasing reported by one method disagrees with the other two are reported. Missing to 100%: cases where all three methods agree. Left: SHAPEIT run with default parameters, corresponding to our ‘ground truth phasing’; right: SHAPEIT run with pedigree information
Fig. 4.
Fig. 4.
Two disjoint unconnected haplotype blocks for which phase information can be inferred from the genotypes
See this image and copyright information in PMC

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