MethylSig

MethylSig is a statistical analysis package for identifying significant DNA methylation differences between groups of biological samples using reduced representation bisulfite sequencing or whole genome bisulfite sequencing data. The tool utilizes a beta-binomial approach to consider read coverage and biological variation across biological samples for a CpG site or region, and incorporates local information to improve group methylation level and/or variance estimation for small sample sizes. A permutation study and simulations show that MethylSig maintains a well-calibrated type-I error and has higher sensitivity compared to alternative methods.