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Oxford University Press, Bioinformatics, 2(36), p. 400-407, 2019

DOI: 10.1093/bioinformatics/btz575

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Haplotype-aware graph indexes

Journal article published in 2019 by Jouni Sirén ORCID, Erik Garrison, Adam M. Novak, Benedict Paten, Richard Durbin
This paper is made freely available by the publisher.
This paper is made freely available by the publisher.

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Abstract

Abstract Motivation The variation graph toolkit (VG) represents genetic variation as a graph. Although each path in the graph is a potential haplotype, most paths are non-biological, unlikely recombinations of true haplotypes. Results We augment the VG model with haplotype information to identify which paths are more likely to exist in nature. For this purpose, we develop a scalable implementation of the graph extension of the positional Burrows–Wheeler transform. We demonstrate the scalability of the new implementation by building a whole-genome index of the 5008 haplotypes of the 1000 Genomes Project, and an index of all 108 070 Trans-Omics for Precision Medicine Freeze 5 chromosome 17 haplotypes. We also develop an algorithm for simplifying variation graphs for k-mer indexing without losing any k-mers in the haplotypes. Availability and implementation Our software is available at https://github.com/vgteam/vg, https://github.com/jltsiren/gbwt and https://github.com/jltsiren/gcsa2. Supplementary information Supplementary data are available at Bioinformatics online.