DiffMethylTools: a toolbox of the detection, annotation and visualization of differential DNA methylation

DNA methylation is a fundamental epigenetic mechanism, and its significant changes (i.e., differential methylation) regulate gene expression, cell-type specification and disease progression without altering the underlying DNA sequence. Differential methylation was usually detected via existing statistical tools by comparing two groups of methyomes (i.e. whole-genome methylation profiles) and has wide applications of various downstream investigations for human disease studies. However, few toolboxes were available to efficiently streamline methylation investigation by integrating robust detection, annotation and visualization of differential methylation. Also, differential methylation detected via tools has poor reproducibility and no tools were tested on the increasing volume of long read methylomes. To address these issues, we introduced DiffMethylTools, an end-to-end solution to eliminate analytical and computational difficulties for differential methylation dissection. Comparison of detection performance on six datasets including three long-read methylomes demonstrated that DiffMethylTools achieved overall better performance of detecting differential methylation than existing tools like MethylKit, DSS, MethylSig, and bsseq. Besides, DiffMethylTools supported versatile input formats for seamless transition from upstream methylation detection tools, and offered diverse annotations and visualizations to facilitate downstream investigations. DiffMethylTools therefore offered a robust, interpretable, and user-friendly solution for differential methylation investigation, benefiting the dissection of methylation's roles in human disease studies.