title: Fast and sensitive mapping of bisulfite-treated sequencing data.
abstract: BACKGROUND
  Cytosine DNA methylation is one of the major epigenetic modifications and influences gene expression, developmental processes, X-chromosome inactivation, and genomic imprinting. Aberrant methylation is furthermore known to be associated with several diseases including cancer. The gold standard to determine DNA methylation on genome-wide scales is 'bisulfite sequencing': DNA fragments are treated with sodium bisulfite resulting in the conversion of unmethylated cytosines into uracils, whereas methylated cytosines remain unchanged. The resulting sequencing reads thus exhibit asymmetric bisulfite-related mismatches and suffer from an effective reduction of the alphabet size in the unmethylated regions, rendering the mapping of bisulfite sequencing reads computationally much more demanding. As a consequence, currently available read mapping software often fails to achieve high sensitivity and in many cases requires unrealistic computational resources to cope with large real-life datasets.
  
  
  RESULTS
  In this study, we present a seed-based approach based on enhanced suffix arrays in conjunction with Myers bit-vector algorithm to efficiently extend seeds to optimal semi-global alignments while allowing for bisulfite-related substitutions. It outperforms most current approaches in terms of sensitivity and performs time-competitive in mapping hundreds of millions of sequencing reads to vertebrate genomes.
  
  
  BACKGROUND
  The software segemehl is freely available at http://www.bioinf.uni-leipzig.de/Software/segemehl.
authors.affiliation: Interdisciplinary Center for Bioinformatics and Bioinformatics Group, Department of Computer Science, University Leipzig, 04107 Leipzig, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Otto
authors.forename: Peter F
authors.initials: PF
authors.lastname: Stadler
authors.forename: Steve
authors.initials: S
authors.lastname: Hoffmann
mesh_terms: D000465:Algorithms; D003596:Cytosine / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D019175:DNA Methylation; D016678:Genome; D006801:Humans; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D013447:Sulfites
chemical_list: D013447:Sulfites; D003596:Cytosine; D004247:DNA; C009279:sodium bisulfite