With advances in next generation sequencing technologies, bisulfite conversion of genomic DNA followed by sequencing has become the predominant technique for quantifying DNA methylation genome-wide at single base resolution. A large number of computational approaches are available in the literature for identifying differentially methylated regions in bisulfite sequencing data, with more being developed continuously. Here, we focus on a comprehensive evaluation of commonly used differential methylation analysis methods to lay out potential strengths and limitations of each method. We find that there are large differences among methods and there is no single method always ranks first in all benchmarking. Moreover, smoothing seems help to improve the performance much and small number of replicates brings more difficulties in computational analysis of BS-seq data rather than low sequencing depth.

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2018-08-06