title: Detection of differentially methylated regions from whole-genome bisulfite sequencing data without replicates.
abstract: DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Recent developments in whole genome bisulfite sequencing (WGBS) technology have enabled genome-wide measurements of DNA methylation at single base pair resolution. Many experiments have been conducted to compare DNA methylation profiles under different biological contexts, with the goal of identifying differentially methylated regions (DMRs). Due to the high cost of WGBS experiments, many studies are still conducted without biological replicates. Methods and tools available for analyzing such data are very limited.We develop a statistical method, DSS-single, for detecting DMRs from WGBS data without replicates. We characterize the count data using a rigorous model that accounts for the spatial correlation of methylation levels, sequence depth and biological variation. We demonstrate that using information from neighboring CG sites, biological variation can be estimated accurately even without replicates. DMR detection is then carried out via a Wald test procedure. Simulations demonstrate that DSS-single has greater sensitivity and accuracy than existing methods, and an analysis of H1 versus IMR90 cell lines suggests that it also yields the most biologically meaningful results. DSS-single is implemented in the Bioconductor package DSS.
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University. 1518 Clifton Road. Atlanta, GA 30322, USA hao.wu@emory.edu.
authors.forename: Hao
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Mathematics and Computer Science, Emory University. 400 Dowman Dr., W401. Atlanta, GA 30322, USA.
authors.forename: Tianlei
authors.initials: T
authors.lastname: Xu
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University. 1518 Clifton Road. Atlanta, GA 30322, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Mathematics and Computer Science, Emory University. 400 Dowman Dr., W401. Atlanta, GA 30322, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University. 1518 Clifton Road. Atlanta, GA 30322, USA.
authors.forename: Ben
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University. 615 Michael Street, Atlanta, GA 30322, USA.
authors.forename: Bing
authors.initials: B
authors.lastname: Yao
authors.affiliation: Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University. 1518 Clifton Road. Atlanta, GA 30322, USA.
authors.forename: Zhaohui
authors.initials: Z
authors.lastname: Qin
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University. 615 Michael Street, Atlanta, GA 30322, USA.
authors.forename: Peng
authors.initials: P
authors.lastname: Jin
authors.affiliation: Department of Human Genetics, School of Medicine, Emory University. 615 Michael Street, Atlanta, GA 30322, USA.
authors.forename: Karen N
authors.initials: KN
authors.lastname: Conneely
mesh_terms: D002460:Cell Line; D019175:DNA Methylation; D003627:Data Interpretation, Statistical; D023281:Genomics / Q000379:methods; D006801:Humans; D017422:Sequence Analysis, DNA / Q000379:methods*; D013447:Sulfites
chemical_list: D013447:Sulfites; C042345:hydrogen sulfite