title: AKSmooth: enhancing low-coverage bisulfite sequencing data via kernel-based smoothing.
abstract: Whole-genome bisulfite sequencing (WGBS) is an approach of growing importance. It is the only approach that provides a comprehensive picture of the genome-wide DNA methylation profile. However, obtaining a sufficient amount of genome and read coverage typically requires high sequencing costs. Bioinformatics tools can reduce this cost burden by improving the quality of sequencing data. We have developed a statistical method Ajusted Local Kernel Smoother (AKSmooth) that can accurately and efficiently reconstruct the single CpG methylation estimate across the entire methylome using low-coverage bisulfite sequencing (Bi-Seq) data. We demonstrate the AKSmooth performance on the low-coverage (~ 4 ×) DNA methylation profiles of three human colon cancer samples and matched controls. Under the best set of parameters, AKSmooth-curated data showed high concordance with the gold standard high-coverage sample (Pearson 0.90), outperforming the popular analogous method. In addition, AKSmooth showed computational efficiency with runtime benchmark over 4.5 times better than the reference tool. To summarize, AKSmooth is a simple and efficient tool that can provide an accurate human colon methylome estimation profile from low-coverage WGBS data. The proposed method is implemented in R and is available at https://github.com/Junfang/AKSmooth.
authors.affiliation: Center for Bioinformatics, Saarland University, Saarbrücken 66123, Germany , Department of Genetics, Saarland University, Saarbrücken 66123, Germany.
authors.forename: Junfang
authors.initials: J
authors.lastname: Chen
authors.forename: Pavlo
authors.initials: P
authors.lastname: Lutsik
authors.forename: Ruslan
authors.initials: R
authors.lastname: Akulenko
authors.forename: Jörn
authors.initials: J
authors.lastname: Walter
authors.forename: Volkhard
authors.initials: V
authors.lastname: Helms
mesh_terms: D000465:Algorithms; D001483:Base Sequence; D002874:Chromosome Mapping / Q000379:methods; D003110:Colonic Neoplasms / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics*; D004273:DNA, Neoplasm / Q000737:chemistry / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D017422:Sequence Analysis, DNA / Q000379:methods*; D012984:Software; D013447:Sulfites / Q000737:chemistry
chemical_list: D004273:DNA, Neoplasm; D013447:Sulfites; C009279:sodium bisulfite
keywords: DNA methylation; read coverage; whole-genome bisulfite sequencing