Cytosine methylation of DNA serves as an important epigenetic mechanism to control gene expression, silencing or genomic imprinting both during development and in the adult (Law and Jacobsen, 2010). Aberrant methylation has been associated with a variety of diseases, including cancer (Robertson, 2005). Current massively parallel sequencing methods to study DNA methylation include enrichment-based methods such as methylated DNA immunoprecipitation (MeDIP-Seq) or methylated DNA binding domain sequencing (MBD-Seq), as well as direct sequencing of sodium bisulfite-treated DNA (BS-Seq) [methods compared in (Harris et al., 2010)].