Bisulfite sequencing (BS-seq) technology measures DNA methylation at single nucleotide resolution.A key task in BS-seq data analysis is to identify differentially methylation (DM) under different conditions.Here we provide a tutorial for BS-seq DM analysis using Bioconductor package DSS.DSS uses a beta-binomial model to characterize the sequence counts from BS-seq,and implements rigorous statistical method for hypothesis testing.It provides flexible functionalities for a variety of DM analyses.