title: QDMR: a quantitative method for identification of differentially methylated regions by entropy.
abstract: DNA methylation plays critical roles in transcriptional regulation and chromatin remodeling. Differentially methylated regions (DMRs) have important implications for development, aging and diseases. Therefore, genome-wide mapping of DMRs across various temporal and spatial methylomes is important in revealing the impact of epigenetic modifications on heritable phenotypic variation. We present a quantitative approach, quantitative differentially methylated regions (QDMRs), to quantify methylation difference and identify DMRs from genome-wide methylation profiles by adapting Shannon entropy. QDMR was applied to synthetic methylation patterns and methylation profiles detected by methylated DNA immunoprecipitation microarray (MeDIP-chip) in human tissues/cells. This approach can give a reasonable quantitative measure of methylation difference across multiple samples. Then DMR threshold was determined from methylation probability model. Using this threshold, QDMR identified 10,651 tissue DMRs which are related to the genes enriched for cell differentiation, including 4740 DMRs not identified by the method developed by Rakyan et al. QDMR can also measure the sample specificity of each DMR. Finally, the application to methylation profiles detected by reduced representation bisulphite sequencing (RRBS) in mouse showed the platform-free and species-free nature of QDMR. This approach provides an effective tool for the high-throughput identification of potential functional regions involved in epigenetic regulation.
authors.affiliation: College of Bioinformatics Science and Technology, Harbin Medical University, Harbin 150081, China. yanyou1225@yahoo.com.cn
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Hongbo
authors.initials: H
authors.lastname: Liu
authors.forename: Jie
authors.initials: J
authors.lastname: Lv
authors.forename: Xue
authors.initials: X
authors.lastname: Xiao
authors.forename: Jiang
authors.initials: J
authors.lastname: Zhu
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Liu
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Su
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
mesh_terms: D000818:Animals; D019175:DNA Methylation; D019277:Entropy; D015870:Gene Expression; D023281:Genomics / Q000379:methods*; D006657:Histones / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D012984:Software
chemical_list: D006657:Histones