title: A mostly traditional approach improves alignment of bisulfite-converted DNA.
abstract: Cytosines in genomic DNA are sometimes methylated. This affects many biological processes and diseases. The standard way of measuring methylation is to use bisulfite, which converts unmethylated cytosines to thymines, then sequence the DNA and compare it to a reference genome sequence. We describe a method for the critical step of aligning the DNA reads to the correct genomic locations. Our method builds on classic alignment techniques, including likelihood-ratio scores and spaced seeds. In a realistic benchmark, our method has a better combination of sensitivity, specificity and speed than nine other high-throughput bisulfite aligners. This study enables more accurate and rational analysis of DNA methylation. It also illustrates how to adapt general-purpose alignment methods to a special case with distorted base patterns: this should be informative for other special cases such as ancient DNA and AT-rich genomes.
authors.affiliation: Computational Biology Research Center, National Institute for Advanced Industrial Science and Technology (AIST), 2-4-7 Aomi, Koto-ku, Tokyo 135-0064, Japan. martin@cbrc.jp
authors.forename: Martin C
authors.initials: MC
authors.lastname: Frith
authors.forename: Ryota
authors.initials: R
authors.lastname: Mori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Asai
mesh_terms: D004247:DNA / Q000737:chemistry; D019175:DNA Methylation; D015894:Genome, Human; D006801:Humans; D012091:Repetitive Sequences, Nucleic Acid; D016415:Sequence Alignment / Q000379:methods*; D017422:Sequence Analysis, DNA; D013447:Sulfites
chemical_list: D013447:Sulfites; D004247:DNA; C042345:hydrogen sulfite