MethylCRF, an algorithm for estimating absolute methylation levels at single CpG resolution from methylation enrichment and restriction enzyme sequencing methods

Abstract

We introduce MethylCRF, a novel Conditional Random Fields-based algorithm to integrate methylated DNA immunoprecipitation (MeDIP-seq) and methylationsensitive restriction enzyme (MRE-seq) sequencing data to predict DNA methylation levels at single CpG resolution. MethylCRF was benchmarked for accuracy against Infinium arrays, RRBS, whole-genome shotgun-bisulfite (WGBS) sequencing and locus specific-bisufite sequencing on the same DNA. MethylCRF transformation of MeDIP/MRE was equivalent to a biological replicate of WGBS in quantification, coverage and resolution, providing a lower cost and widely accessible strategy to create full methylomes. © 2013 Springer-Verlag.