Research Article

Spatially Enhanced Differential RNA Methylation Analysis from Affinity-Based Sequencing Data with Hidden Markov Model

Figure 2

Comparison of differential methylation analysis methods. This figure shows the difference between existing peak-based differential analysis method and the proposed method. Started from aligned reads, the left part of this figure shows how exomePeak conducts differential analysis. It firstly identifies a single methylation site and then decides whether the methylation site as a whole is differentially methylated or not. However, the newly proposed method will split the testing region into multiple adjacent small bins and then will integrate their dependency with HMM for more accurate identification of differential methylation site. In the above example, the RNA methylation site detected using exomePeak method may consist of two methylation residuals, and only the one on the right side is differentially methylated in this case-control study. The proposed FET-HMM method is likely to work better than peak-based exomePeak method under this scenario.