title: MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution.
abstract: Organisms and cells, in response to environmental influences or during development, undergo considerable changes in DNA methylation on a genome-wide scale, which are linked to a variety of biological processes. Using MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively costly. In this study, we develop a novel approach, named MBRidge, to detect the methylation levels of repertoire CpGs, by innovatively introducing C-hydroxylmethylated adapters and bisulfate treatment into the MeDIP-seq protocol and employing ridge regression in data analysis. A systematic evaluation of DNA methylome in a human ovarian cell line T29 showed that MBRidge achieved high correlation (R > 0.90) with much less cost (∼10%) in comparison with MethylC-seq. We further applied MBRidge to profiling DNA methylome in T29H, an oncogenic counterpart of T29's. By comparing methylomes of T29H and T29, we identified 131790 differential methylation regions (DMRs), which are mainly enriched in carcinogenesis-related pathways. These are substantially different from 7567 DMRs that were obtained by RRBS and related with cell development or differentiation. The integrated analysis of DMRs in the promoter and expression of DMR-corresponding genes revealed that DNA methylation enforced reverse regulation of gene expression, depending on the distance from the proximal DMR to transcription starting sites in both mRNA and lncRNA. Taken together, our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes.
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Wanshi
authors.initials: W
authors.lastname: Cai
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Fengbiao
authors.initials: F
authors.lastname: Mao
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Huajing
authors.initials: H
authors.lastname: Teng
authors.affiliation: Experimental Medicine Section, NIDCR, National Institutes of Health, Bethesda, MD 20892, USA.
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Fangqing
authors.initials: F
authors.lastname: Zhao
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325035, China sunzs@mail.biols.ac.cn iamwujy@gmail.com.
authors.forename: Jinyu
authors.initials: J
authors.lastname: Wu
authors.affiliation: Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing 100101, China Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou 325035, China sunzs@mail.biols.ac.cn iamwujy@gmail.com.
authors.forename: Zhong Sheng
authors.initials: ZS
authors.lastname: Sun
mesh_terms: D001483:Base Sequence; D002138:Calibration; D045744:Cell Line, Tumor; D003362:Cost-Benefit Analysis; D019175:DNA Methylation / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008954:Models, Biological; D010051:Ovarian Neoplasms / Q000235:genetics; D012044:Regression Analysis; D015203:Reproducibility of Results; D017422:Sequence Analysis, DNA / Q000191:economics* / Q000379:methods*; D012984:Software
keywords: DNA methylome; MB-seq; ridge regression; single-base resolution