Abstract
BackgroundThe advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input. Whereas the use of Infinium Human Methylation BeadChips has shown great utility in clinical studies, no equivalent tool is available for rodent animal samples. We examined the feasibility of using the new Infinium MethylationEPIC BeadChip for studying DNA methylation in mouse.ResultsIn silico, we identified 19,420 EPIC probes (referred as mEPIC probes), which align with a unique best alignment score to the bisulfite converted reference mouse genome mm10. Further annotation revealed that 85% of mEPIC probes overlapped with mm10.refSeq genes at different genomic features including promoters (TSS1500 and TSS200), 1st exons, 5′UTRs, 3′UTRs, CpG islands, shores, shelves, open seas and FANTOM5 enhancers. Hybridization of mouse samples to Infinium Human MethylationEPIC BeadChips showed successful measurement of mEPIC probes and reproducibility between inter-array biological replicates. Finally, we demonstrated the utility of mEPIC probes for data exploration such as hierarchical clustering.ConclusionsGiven the absence of cost and labor convenient genome-wide technologies in the murine system, our findings show that the Infinium MethylationEPIC BeadChip platform is suitable for investigation of the mouse methylome. Furthermore, we provide the “mEPICmanifest” with genomic features, available to users of Infinium Human MethylationEPIC arrays for mouse samples.
Highlights
The advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input
BS treatment converts unmethylated cytosines into uracils, which during the whole genome amplification step are read as thymines, while methylated
We demonstrate the potential usability of Illumina Infinium MethylationEPIC BeadChips for mouse samples
Summary
The advent of array-based genome-wide DNA methylation methods has enabled quantitative measurement of single CpG methylation status at relatively low cost and sample input. Genome-wide DNA methylation arrays allow absolute measurement of single CpG methylation status located at various regulatory regions throughout the human genome at relatively low cost, thereby giving great utility in clinical studies. The use of Infinium HumanMethylation450 BeadChips (HM450) in epigenome-wide association studies in large cohorts has proven a very promising approach in deciphering putative pathogenic mechanisms influenced by both genetic and environmental factors [3, 4]. Such tools are failing to explore DNA methylation in animal models, such as in mouse, leaving as the only option labor-consuming and costly methodologies that often require more advanced bioinformatics resources
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