Detailed biological knowledge about the potential importance of the methylome is typically lacking for common diseases. Therefore, methylome-wide association studies (MWAS) are critical to detect disease relevant methylation sites. Methyl-CpG-binding domain sequencing (MBD-seq) offers potential advantages compared to antibody-based enrichment, but performance depends critically on using an optimal protocol. Using an optimized protocol, MBD-seq can approximate the sensitivity/specificity obtained with whole-genome bisulfite sequencing, but at a fraction of the costs and time to complete the project. Thus, MBD-seq offers a comprehensive first pass at the CpG methylome and is economically feasible with the samples sizes required for MWAS.
Keywords: Affinity-based capture; Blood spots; CpG; Differentially methylated regions; High-dimensional data analysis; MBD-seq; MWAS; Methyl-CpG-binding domain; MethylMiner; Methylome-wide association studies; RaMWAS; Sequencing.