School of Automation from the Northwestern Polytechnical University, China.
Key Laboratory of Information Fusion Technology of Ministry of Education, School of Automation, Northwestern Polytechnical University, China.
Brief Bioinform. 2022 Jul 18;23(4). doi: 10.1093/bib/bbac295.
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.
作为最丰富的 RNA 修饰，N6-甲基腺苷（m6A）在各种 RNA 活性中发挥重要作用，包括基因表达和翻译。随着 MeRIP-seq 技术的快速应用，从同一实验单元中提取了多个组的样本，例如涉及多种病毒/细菌感染或不同的细胞分化阶段。然而，由于缺乏有效的工具，我们目前对于动态 m6A 如何调节基因表达以及在某些生物学过程（例如在此复杂背景下的免疫反应）中的作用知之甚少。为了解决这个问题，我们提出了一种贝叶斯分层混合模型（称为 m6Aexpress-BHM），用于预测具有有限样本的多个 MeRIP-seq 实验中 m6A 对基因表达的调节（m6A-reg-exp）。m6Aexpress-BHM 在模拟数据上的综合评估表明其具有较高的预测精度和鲁棒性。将 m6Aexpress-BHM 应用于三个真实数据集（即黄病毒感染、细菌感染时间点和树突状细胞分化阶段），我们预测了更多具有阳性调节模式的 m6A-reg-exp 基因，这些基因显著参与先天免疫或适应性免疫途径，揭示了 m6A 在免疫反应中调节功能的潜在机制。此外，我们还发现 m6A 可能通过调节其相互作用的基因来影响 PD-1/PD-L1 的表达。这些结果证明了 m6Aexpress-BHM 的强大功能，帮助我们理解 m6A 在免疫系统中的调节功能。
