A test for detecting differentially methylated regions

DNA methylation is one of the most important phenomena in epigenetics. Because the DNA methylation process regulates gene expression without altering the corresponding DNA sequences, it can explain many biological processes such as onset of cancer, aging, and differentiation of species. Therefore, detecting differentially methylated region (DMR) between groups has been considered one of important analyses in epigenetics. For the datasets generated by the methylated DNA immunoprecipitation (MeDIP) technique, DMR analysis has employed the previous methods developed for the microarray-based gene expression dataset. However, for the datasets generated by more recent bisulfite-sequencing (BS-seq) technologies, totally different approaches need to be used. Unfortunately, only a few methods are available for DMR analysis among which the Fisher's exact test is most widely used. We first propose a new DMR test for BS-seq data. Our approach employs Cochran-Mantel-Hantzel (CMH) test and extend it by incorporating correlation structures between adjacent CpG cytosine sites. Then we apply it to a real dataset of two subspecies of honeybee for detecting DMR regions.