Validation of a DNA Methylation Microarray for 850,000 CpG Sites of the Human Genome Enriched in Enhancer Sequences

TLDR

DNA methylation is the best known epigenetic mark, and altered methylomes are observed in cancer and other pathologies. The study aims to validate the newly developed MethylationEPIC BeadChip microarray covering over 850,000 CpG sites. The authors performed technical and biological validation of the array, building on the success of the 450K platform. The array contains >90 % of the 450K sites, adds 333,265 enhancer CpGs, and demonstrates high reproducibility, consistency across sample types, and utility for 5‑hmC, confirming its value for genome‑wide methylation profiling.

Abstract

DNA methylation is the best known epigenetic mark. Cancer and other pathologies show an altered DNA methylome. However, delivering complete DNA methylation maps is compromised by the price and labor-intensive interpretation of single nucleotide methods.Following the success of the HumanMethylation450 BeadChip (Infinium) methylation microarray (450K), we report the technical and biological validation of the newly developed MethylationEPIC BeadChip (Infinium) microarray that covers over 850,000 CpG methylation sites (850K). The 850K microarray contains >90% of the 450K sites, but adds 333,265 CpGs located in enhancer regions identified by the ENCODE and FANTOM5 projects.The 850K array demonstrates high reproducibility at the 450K CpG sites, is consistent among technical replicates, is reliable in the matched study of fresh frozen versus formalin-fixed paraffin-embeded samples and is also useful for 5-hydroxymethylcytosine. These results highlight the value of the MethylationEPIC BeadChip as a useful tool for the analysis of the DNA methylation profile of the human genome.