title: Discovering motifs that induce sequencing errors.
abstract: BACKGROUND
  Elevated sequencing error rates are the most predominant obstacle in single-nucleotide polymorphism (SNP) detection, which is a major goal in the bulk of current studies using next-generation sequencing (NGS). Beyond routinely handled generic sources of errors, certain base calling errors relate to specific sequence patterns. Statistically principled ways to associate sequence patterns with base calling errors have not been previously described. Extant approaches either incur decisive losses in power, due to relating errors with individual genomic positions rather than motifs, or do not properly distinguish between motif-induced and sequence-unspecific sources of errors.
  
  
  RESULTS
  Here, for the first time, we describe a statistically rigorous framework for the discovery of motifs that induce sequencing errors. We apply our method to several datasets from Illumina GA IIx, HiSeq 2000, and MiSeq sequencers. We confirm previously known error-causing sequence contexts and report new more specific ones.
  
  
  CONCLUSIONS
  Checking for error-inducing motifs should be included into SNP calling pipelines to avoid false positives. To facilitate filtering of sets of putative SNPs, we provide tracks of error-prone genomic positions (in BED format).
  
  
  BACKGROUND
  http://discovering-cse.googlecode.com.
authors.affiliation: Life Sciences Group, Centrum Wiskunde & Informatica, Amsterdam, Netherlands. T.Marschall@cwi.nl.
authors.forename: Manuel
authors.initials: M
authors.lastname: Allhoff
authors.forename: Alexander
authors.initials: A
authors.lastname: Schönhuth
authors.forename: Marcel
authors.initials: M
authors.lastname: Martin
authors.forename: Ivan G
authors.initials: IG
authors.lastname: Costa
authors.forename: Sven
authors.initials: S
authors.lastname: Rahmann
authors.forename: Tobias
authors.initials: T
authors.lastname: Marschall
mesh_terms: D000465:Algorithms; D004247:DNA / Q000737:chemistry; D016678:Genome; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D059372:Nucleotide Motifs; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*
chemical_list: D004247:DNA