License: Creative Commons Attribution 3.0 Unported license (CC BY 3.0)
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DOI: 10.4230/LIPIcs.WABI.2019.17
URN: urn:nbn:de:0030-drops-110470
URL: http://dagstuhl.sunsite.rwth-aachen.de/volltexte/2019/11047/
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Jain, Chirag ; Zhang, Haowen ; Dilthey, Alexander ; Aluru, Srinivas

Validating Paired-End Read Alignments in Sequence Graphs

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LIPIcs-WABI-2019-17.pdf (0.5 MB)

Abstract

Graph based non-linear reference structures such as variation graphs and colored de Bruijn graphs enable incorporation of full genomic diversity within a population. However, transitioning from a simple string-based reference to graphs requires addressing many computational challenges, one of which concerns accurately mapping sequencing read sets to graphs. Paired-end Illumina sequencing is a commonly used sequencing platform in genomics, where the paired-end distance constraints allow disambiguation of repeats. Many recent works have explored provably good index-based and alignment-based strategies for mapping individual reads to graphs. However, validating distance constraints efficiently over graphs is not trivial, and existing sequence to graph mappers rely on heuristics. We introduce a mathematical formulation of the problem, and provide a new algorithm to solve it exactly. We take advantage of the high sparsity of reference graphs, and use sparse matrix-matrix multiplications (SpGEMM) to build an index which can be queried efficiently by a mapping algorithm for validating the distance constraints. Effectiveness of the algorithm is demonstrated using real reference graphs, including a human MHC variation graph, and a pan-genome de-Bruijn graph built using genomes of 20 B. anthracis strains. While the one-time indexing time can vary from a few minutes to a few hours using our algorithm, answering a million distance queries takes less than a second.

BibTeX - Entry

@InProceedings{jain_et_al:LIPIcs:2019:11047,
  author =	{Chirag Jain and Haowen Zhang and Alexander Dilthey and Srinivas Aluru},
  title =	{{Validating Paired-End Read Alignments in Sequence Graphs}},
  booktitle =	{19th International Workshop on Algorithms in Bioinformatics (WABI 2019)},
  pages =	{17:1--17:13},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-123-8},
  ISSN =	{1868-8969},
  year =	{2019},
  volume =	{143},
  editor =	{Katharina T. Huber and Dan Gusfield},
  publisher =	{Schloss Dagstuhl--Leibniz-Zentrum fuer Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{http://drops.dagstuhl.de/opus/volltexte/2019/11047},
  URN =		{urn:nbn:de:0030-drops-110470},
  doi =		{10.4230/LIPIcs.WABI.2019.17},
  annote =	{Keywords: Sequence graphs, read mapping, index, sparse matrix-matrix multiplication}
}

Keywords: Sequence graphs, read mapping, index, sparse matrix-matrix multiplication
Collection: 19th International Workshop on Algorithms in Bioinformatics (WABI 2019)
Issue Date: 2019
Date of publication: 03.09.2019

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