Data-Driven-Based Approach to Identifying Differentially Methylated Regions Using Modified 1D Ising Model

Background. DNA methylation is essential for regulating gene expression, and the changes of DNA methylation status are commonly discovered in disease. Therefore, identification of differentially methylation patterns, especially differentially methylated regions (DMRs), in two different groups is important for understanding the mechanism of complex diseases. Few tools exist for DMR identification through considering features of methylation data, but there is no comprehensive integration of the characteristics of DNA methylation data in current methods. Results. Accounting for the characteristics of methylation data, such as the correlation characteristics of neighboring CpG sites and the high heterogeneity of DNA methylation data, we propose a data-driven approach for DMR identification through evaluating the energy of single site using modified 1D Ising model. Applied to both simulated and publicly available datasets, our approach is compared with other popular methods in terms of performance. Simulated results show that our method is more sensitive than competing methods. Applied to the real data, our method can identify more common DMRs than DMRcate, ProbeLasso, and Wang's methods with a high overlapping ratio. Also, the necessity of integrating the heterogeneity and correlation characteristics in identifying DMR is shown through comparing results with only considering mean or variance signals and without considering relationship of neighboring CpG sites, respectively. Through analyzing the number of DMRs identified in real data located in different genomic regions, we find that about 90% DMRs are located in CGI which always regulates the expression of genes. It may help us understand the functional effect of DNA methylation on disease.

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