Combining MeDIP-seq and MRE-seq to estimate single CpG methylation genome wide

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No current assay of DNA methylation provides single-CpG resolution, comprehensive genome-wide coverage, and cost feasibility for a typical laboratory. To address this gap, we introduce methylCRF, a novel Conditional Random Field-based algorithm that integrates methylated DNA immunoprecipitation (MeDIP-seq) and methylation-sensitive restriction enzyme (MRE-seq) sequencing data to predict DNA methylation levels at single CpG resolution. Our method is a combined computational and experimental strategy to produce DNA methylomes of all 28 million CpGs in the human genome for a fraction (<10%) of the cost of whole genome bisulfite sequencing methods.