m 6  Aexpress-BHM: predicting m6A regulation of gene expression in multiple-groups context by a Bayesian hierarchical mixture model.

As the most abundant RNA modification, N6-methyladenosine (m6A) plays an important role in various RNA activities including gene expression and translation. With the rapid application of MeRIP-seq technology, samples of multiple groups, such as the involved multiple viral/ bacterial infection or distinct cell differentiation stages, are extracted from same experimental unit. However, our current knowledge about how the dynamic m6A regulating gene expression and the role in certain biological processes (e.g. immune response in this complex context) is largely elusive due to lack of effective tools. To address this issue, we proposed a Bayesian hierarchical mixture model (called m6Aexpress-BHM) to predict m6A regulation of gene expression (m6A-reg-exp) in multiple groups of MeRIP-seq experiment with limited samples. Comprehensive evaluations of m6Aexpress-BHM on the simulated data demonstrate its high predicting precision and robustness. Applying m6Aexpress-BHM on three real-world datasets (i.e. Flaviviridae infection, infected time-points of bacteria and differentiation stages of dendritic cells), we predicted more m6A-reg-exp genes with positive regulatory mode that significantly participate in innate immune or adaptive immune pathways, revealing the underlying mechanism of the regulatory function of m6A during immune response. In addition, we also found that m6A may influence the expression of PD-1/PD-L1 via regulating its interacted genes. These results demonstrate the power of m6Aexpress-BHM, helping us understand the m6A regulatory function in immune system.