DNAmethylatiearrays

DNAmethylatiearrays are high-throughput platforms used to quantify DNA methylation at hundreds of thousands of CpG sites across the genome in a single experiment. They are commonly applied in epigenome-wide association studies to find methylation differences linked to disease, age, environment, or treatment.

Most arrays rely on bisulfite-treated DNA and hybridization to locus-specific probes. After bisulfite conversion, methylated cytosines remain unchanged while unmethylated cytosines convert to uracil, allowing probes to distinguish methylated versus unmethylated states. The readout is a probe intensity that is converted to methylation proportion, called a beta value (0–1) or an M-value (logit).

Commercially dominant platforms include Illumina Infinium HumanMethylation450 BeadChip (450K) and the Infinium MethylationEPIC BeadChip (850K).

Data processing includes quality control, normalization to remove technical variation (e.g., background, dye bias, probe type bias), and filtering of poor-quality or cross-reactive probes. Typical pipelines use tools such as minfi, meffil, and Genome Studio; downstream analyses use linear models or mixed effects to detect differential methylation.

Applications and limitations: DNAmethylatiearrays enable cost-efficient profiling in large cohorts, useful for EWAS, age estimation, and cell-type deconvolution. Limitations include biased genomic coverage toward CpG-dense regions, potential cross-hybridization, inability to distinguish 5-methylcytosine from 5-hydroxymethylcytosine without specialized assays, and sensitivity to sample composition. Data interpretation requires careful consideration of tissue heterogeneity and batch effects.