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Illumina Infinium DNA Methylation BeadChips represent the most widely used genome-scale DNA methylation assays. Existing strategies for masking Infinium probes overlapping repeats or single nucleotide polymorphisms (SNPs) are based largely on ad hoc assumptions and subjective criteria. In addition, the recently introduced MethylationEPIC (EPIC) array expands on the utility of this platform, but has not yet been well characterized. We present in this paper an extensive characterization of probes on the EPIC and HM450 microarrays, including mappability to the latest genome build, genomic copy number of the 3΄ nested subsequence and influence of polymorphisms including a previously unrecognized color channel switch for Type I probes. We show empirical evidence for exclusion criteria for underperforming probes, providing a sounder basis than current ad hoc criteria for exclusion. In addition, we describe novel probe uses, exemplified by the addition of a total of 1052 SNP probes to the existing 59 explicit SNP probes on the EPIC array and the use of these probes to predict ethnicity. Finally, we present an innovative out-of-band color channel application for the dual use of 62 371 probes as internal bisulfite conversion controls.

Comprehensive characterization, annotation and innovative use of Infinium DNA methylation BeadChip probes