Comparative analysis of Illumina Mouse Methylation BeadChip and reduced-representation bisulfite sequencing for routine DNA methylation analysis

Researching the murine epigenome in disease models has been hampered by the lack of appropriate and cost-effective DNA methylation arrays. Here we perform a comprehensive, comparative analysis between the Mouse Methylation BeadChip (MMB) and reduced-representation bisulfite sequencing (RRBS) in two murine models of colorectal carcinogenesis. We evaluate the coverage, variability, and ability to identify differential DNA methylation of RRBS and MMB. We show that MMB is an effective tool for profiling the murine methylome that performs comparably with RRBS, identifying similar differentially methylated pathways. Although choice of technology is experiment dependent and will be predicated on the underlying biology being probed, these analyses provide insights into the relative strengths and weaknesses of each approach. • The Illumina Mouse Methylation array allows precise measurements of DNA methylation • RRBS and the Mouse Methylation array identify similar aberrantly methylated pathways • Choice of platform should be guided by the underlying biology of the experimental model Array-based platforms have been used extensively to evaluate human DNA methylation, but DNA methylation profiling of model systems has been limited to next-generation sequencing-based approaches. Commercial release of a murine DNA methylation array is of interest to the epigenetics community, but the performance of this platform versus existing sequencing-based methodologies has not been evaluated previously. In this resource article, we attempt to provide insight into the performance of MMB in a real-world setting. Fennell et al. comprehensively compare reduced-representation bisulfite sequencing and the Mouse Methylation BeadChip. We assess the ability of each platform to identify differentially methylated CpGs and pathways, their coverage of different genomic elements, variability and precision of methylation measurements, and other important factors that influence choice of experimental platform.