swDMR: A Sliding Window Approach to Identify Differentially Methylated Regions Based on Whole Genome Bisulfite Sequencing

<div><p>DNA methylation is a widespread epigenetic modification that plays an essential role in gene expression through transcriptional regulation and chromatin remodeling. The emergence of whole genome bisulfite sequencing (WGBS) represents an important milestone in the detection of DNA methylation. Characterization of differential methylated regions (DMRs) is fundamental as well for further functional analysis. In this study, we present swDMR (<a href="http://sourceforge.net/projects/swdmr/" target="_blank">http://sourceforge.net/projects/swdmr/</a>) for the comprehensive analysis of DMRs from whole genome methylation profiles by a sliding window approach. It is an integrated tool designed for WGBS data, which not only implements accessible statistical methods to perform hypothesis test adapted to two or more samples without replicates, but false discovery rate was also controlled by multiple test correction. Downstream analysis tools were also provided, including cluster, annotation and visualization modules. In summary, based on WGBS data, swDMR can produce abundant information of differential methylated regions. As a convenient and flexible tool, we believe swDMR will bring us closer to unveil the potential functional regions involved in epigenetic regulation.</p></div

Comparison of swDMR and CpG_MPs in two and three samples.

<p>(A, D) Venn diagram of DMRs detected by fisher exact test through swDMR and CpG_MPs to two samples respectively. (B, E) Venn diagram of genes with DMRs overlapped in their promoters (promoter: -1.3kb of TSS and +0.2kb of TSS). (C, F) swDMR specific genes with methylation level of hESC, hESC-Fibro and Fibro. Methylation of each CpG ranges from 0 to 1. Red lines represent DMRs of swDMR and CpG_MPs. Blue track represents RefSeq genes.</p

Software of DMR detection.

<p>Software of DMR detection.</p

Results of swDMR.

<p>(A) Length distribution of DMR. (B). Methylation level cluster analysis of three samples (hESC, hESC-Fibro, Firbo). (C) Methylation level boxplot of three samples. (D) Enrichment analysis of genome features (5-UTR, 3-UTR, CDS, Intron, Upstream, Downstream). (E) A specific DMR related to HOXD12 gene.</p

Simulation data and DMR detection comparison.

<p>(A) Simulation DNA methylation level distribution of two samples. (C) Distribution of absolute differential methylation level in DMR. (C) Venn diagram of ComMet (lightgreen), CpG_MPs (darkorchid) and swDMR (cornflowerblue). (D) Scatter plot of DNA methylation level in DMRs of simulation data to three DMR detection methods. Color (ranged from gray to yellow with contour line) represents intensity of DMRs.</p