mHapBrowser: a comprehensive database for visualization and analysis of DNA methylation haplotypes

Abstract

Abstract DNA methylation acts as a vital epigenetic regulatory mechanism involved in controlling gene expression. Advances in sequencing technologies have enabled characterization of methylation patterns at single-base resolution using bisulfite sequencing approaches. However, existing methylation databases have primarily focused on mean methylation levels, overlooking phased methylation patterns. The methylation status of CpGs on individual sequencing reads represents discrete DNA methylation haplotypes (mHaps). Here, we present mHapBrowser, a comprehensive database for visualizing and analyzing mHaps. We systematically processed data of diverse tissues in human, mouse and rat from public repositories, generating mHap format files for 6366 samples. mHapBrowser enables users to visualize eight mHap metrics across the genome through an integrated WashU Epigenome Browser. It also provides an online server for comparing mHap patterns across samples. Additionally, mHap files for all samples can be downloaded to facilitate local processing using downstream analysis toolkits. The utilities of mHapBrowser were demonstrated through three case studies: (i) mHap patterns are associated with gene expression; (ii) changes in mHap patterns independent of mean methylation correlate with differential expression between lung cancer subtypes; and (iii) the mHap metric MHL outperforms mean methylation for classifying tumor and normal samples from cell-free DNA. The database is freely accessible at http://mhap.sibcb.ac.cn/.