License: Creative Commons Attribution 3.0 Unported license (CC BY 3.0)
When quoting this document, please refer to the following
DOI: 10.4230/LIPIcs.WABI.2018.13
URN: urn:nbn:de:0030-drops-93158
URL: http://dagstuhl.sunsite.rwth-aachen.de/volltexte/2018/9315/
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Hartmann, Till ; Rahmann, Sven

Spalter: A Meta Machine Learning Approach to Distinguish True DNA Variants from Sequencing Artefacts

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LIPIcs-WABI-2018-13.pdf (0.4 MB)

Abstract

Being able to distinguish between true DNA variants and technical sequencing artefacts is a fundamental task in whole genome, exome or targeted gene analysis. Variant calling tools provide diagnostic parameters, such as strand bias or an aggregated overall quality for each called variant, to help users make an informed choice about which variants to accept or discard. Having several such quality indicators poses a problem for the users of variant callers because they need to set or adjust thresholds for each such indicator. Alternatively, machine learning methods can be used to train a classifier based on these indicators. This approach needs large sets of labeled training data, which is not easily available.
The new approach presented here relies on the idea that a true DNA variant exists independently of technical features of the read in which it appears (e.g. base quality, strand, position in the read). Therefore the nucleotide separability classification problem - predicting the nucleotide state of each read in a given pileup based on technical features only - should be near impossible to solve for true variants. Nucleotide separability, i.e. achievable classification accuracy, can either be used to distinguish between true variants and technical artefacts directly, using a thresholding approach, or it can be used as a meta-feature to train a separability-based classifier. This article explores both possibilities with promising results, showing accuracies around 90%.

BibTeX - Entry

@InProceedings{hartmann_et_al:LIPIcs:2018:9315,
  author =	{Till Hartmann and Sven Rahmann},
  title =	{{Spalter: A Meta Machine Learning Approach to Distinguish True DNA Variants from Sequencing Artefacts}},
  booktitle =	{18th International Workshop on Algorithms in  Bioinformatics (WABI 2018)},
  pages =	{13:1--13:8},
  series =	{Leibniz International Proceedings in Informatics (LIPIcs)},
  ISBN =	{978-3-95977-082-8},
  ISSN =	{1868-8969},
  year =	{2018},
  volume =	{113},
  editor =	{Laxmi Parida and Esko Ukkonen},
  publisher =	{Schloss Dagstuhl--Leibniz-Zentrum fuer Informatik},
  address =	{Dagstuhl, Germany},
  URL =		{http://drops.dagstuhl.de/opus/volltexte/2018/9315},
  URN =		{urn:nbn:de:0030-drops-93158},
  doi =		{10.4230/LIPIcs.WABI.2018.13},
  annote =	{Keywords: variant calling, sequencing error, technical artefact, meta machine learning, classification}
}

Keywords: variant calling, sequencing error, technical artefact, meta machine learning, classification
Collection: 18th International Workshop on Algorithms in Bioinformatics (WABI 2018)
Issue Date: 2018
Date of publication: 02.08.2018

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