Long-read mapping to repetitive reference sequences using Winnowmap2

Jain, C and Rhie, A and Hansen, NF and Koren, S and Phillippy, AM (2022) Long-read mapping to repetitive reference sequences using Winnowmap2. In: Nature Methods .

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Abstract

Approximately 5�10 of the human genome remains inaccessible due to the presence of repetitive sequences such as segmental duplications and tandem repeat arrays. We show that existing long-read mappers often yield incorrect alignments and variant calls within long, near-identical repeats, as they remain vulnerable to allelic bias. In the presence of a nonreference allele within a repeat, a read sampled from that region could be mapped to an incorrect repeat copy. To address this limitation, we developed a new long-read mapping method, Winnowmap2, by using minimal confidently alignable substrings. Winnowmap2 computes each read mapping through a collection of confident subalignments. This approach is more tolerant of structural variation and more sensitive to paralog-specific variants within repeats. Our experiments highlight that Winnowmap2 successfully addresses the issue of allelic bias, enabling more accurate downstream variant calls in repetitive sequences. © 2022, The Author(s), under exclusive licence to Springer Nature America, Inc.

Item Type:	Journal Article
Publication:	Nature Methods
Publisher:	Nature Research
Additional Information:	The copyright for this article belongs to Nature Research
Keywords:	allele; article; human; paralogy
Department/Centre:	Division of Interdisciplinary Sciences > Computational and Data Sciences
Date Deposited:	18 May 2022 08:50
Last Modified:	18 May 2022 08:50
URI:	https://eprints.iisc.ac.in/id/eprint/71831

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