title: MeSiC: A Model-Based Method for Estimating 5 mC Levels at Single-CpG Resolution from MeDIP-seq.
abstract: As the fifth base in mammalian genome, 5-methylcytosine (5 mC) is essential for many biological processes including normal development and disease. Methylated DNA immunoprecipitation sequencing (MeDIP-seq), which uses anti-5 mC antibodies to enrich for methylated fraction of the genome, is widely used to investigate methylome at a resolution of 100-500 bp. Considering the CpG density-dependent bias and limited resolution of MeDIP-seq, we developed a Random Forest Regression (RFR) model method, MeSiC, to estimate DNA methylation levels at single-base resolution. MeSiC integrated MeDIP-seq signals of CpG sites and their surrounding neighbors as well as genomic features to construct genomic element-dependent RFR models. In the H1 cell line, a high correlation was observed between MeSiC predictions and actual 5 mC levels. Meanwhile, MeSiC enabled to calibrate CpG density-dependent bias of MeDIP-seq signals. Importantly, we found that MeSiC models constructed in the H1 cell line could be used to accurately predict DNA methylation levels for other cell types. Comparisons with methylCRF and MEDIPS showed that MeSiC achieved comparable and even better performance. These demonstrate that MeSiC can provide accurate estimations of 5 mC levels at single-CpG resolution using MeDIP-seq data alone.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.|Key Laboratory of Cardiovascular Medicine Research, Harbin Medical University, Ministry of Education.
authors.forename: Yun
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Fulong
authors.initials: F
authors.lastname: Yu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Pang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Zhao
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Guanxiong
authors.initials: G
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Liu
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Hongyi
authors.initials: H
authors.lastname: Zhang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Fan
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Genetics, Harbin Medical University, Harbin 150081, Heilongjiang 150081, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Pang
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin, Heilongjiang 150081, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
mesh_terms: D044503:5-Methylcytosine; D000818:Animals; D019295:Computational Biology / Q000379:methods*; D018899:CpG Islands; D019175:DNA Methylation; D023281:Genomics / Q000379:methods; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015233:Models, Statistical; D015203:Reproducibility of Results
chemical_list: D044503:5-Methylcytosine