Many previous BS-Seq programs were solely mapping applications, which meant that extracting the underlying methylation data required a lot of post-processing and computational knowledge. Bismark aims to generate a bisulfite mapping output that can be readily explored by bench scientists. Thus, in addition to the alignment process Bismark determines the methylation state of each cytosine position in the read (Fig. 1B). DNA methylation in mammals is thought to occur predominantly at CpG dinucleotides; however, a certain amount of non-CpG methylation has been shown in embryonic stem cells (Lister et al., 2009). In plants, methylation is quite common in both the symmetric CpG or CHG, and asymmetric CHH context (whereby H can be either A, T or C) (Feng et al., 2010; Law and Jacobsen, 2010). To enable methylation analysis in different sequence contexts and/or model organisms, methylation calls in Bismark take the surrounding sequence context into consideration and discriminate between cytosines in CpG, CHG and CHH context.
