MBRidge: an accurate and cost-effective method for profiling DNA methylome at single-base resolution

作     者：Wanshi Cai Fengbiao Mao Huajing Teng Tao Cai Fangqing Zhao Jinyu Wu Zhong Sheng Sun 

作者机构：Beijing Institutes of Life ScienceChinese Academy of SciencesBeijing 100101China University of Chinese Academy of SciencesBeijing 100049China Institute of ZoologyChinese Academy of SciencesBeijing 100101China Experimental Medicine SectionNIDCRNational Institutes of HealthBethesdaMD 20892USA Institute of Genomic MedicineWenzhou Medical UniversityWenzhou 325035China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2015年第7卷第4期

页      面：299-313页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by grants from the NationalHigh Technology Research and Development Program of China(2012AA02A201,2012AA02A202) China-Canada Collaboration Project from the Ministry of Science and Technology of China(2011DFA30670) the National Natural Science Foundation of China(31171236/C060503) the Astra Zeneca Innovation Centre China 

主　　题：DNA methylome MB-seq ridge regression single-base resolution 

摘      要：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 *** MethylC-seq to decipher DNA methylome at single-base resolution is prohibitively *** 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(R0.90)with much less cost(∼10%)in comparison with *** further applied MBRidge to profiling DNA methylome in T29H,an oncogenic counterpart of T29’*** comparing methylomes of T29H and T29,we identified 131790 differential methylation regions(DMRs),which are mainly enriched in carcinogenesis-related *** are substantially different from7567 DMRs that were obtained by RRBS and related with cell development or *** integrated analysis ofDMRsin the promoterand expression of DMR-corresponding genes revealed thatDNAmethylation enforced reverse regulation of gene expression,depending on the distance fromthe proximalDMRto transcription starting sites in both mRNA and *** together,our results demonstrate that MBRidge is an efficient and cost-effective method that can be widely applied to profiling DNA methylomes.