RNA甲基化修饰高通量测序数据的生物信息方法开发以及RNA甲基化修饰调控网络的系统重建

With the development of high-throughput sequencing technique, especially MeRIP-Seq, RNA epigenetics has drawn more and more attention. Recent studies have shown that N6-MethylAdenosine (m6A) regulates a number of important biological functions, including, cell differentiation, translation, etc.. Systematically unveil the regulatory mechanism of RNA methylation will greatly facilitate relevant studies...RNA methylation is directly related by enzymes. Due to the preference and specificity of enzymes, the handful known RNA methyltransferases and demethylases target at different RNA methylation sites, and the regulatory mechanism of tens of thousands of RNA methylation sites by enzymes appears to have a network structure. We propose here to model the regulatory mechanism of RNA methylome with a Bayesian network generative model, so as to infer the direct regulatory relationship between enzymes and the RNA methylation sites, unveiling the gene regulatory network at epitranscriptomic layer, and eventually, explore the possible application of RNA methylome regulatory network in disease treatment. Meanwhile, we will develop essential bioinformatics approaches for the analysis of RNA methylation-related high throughput sequencing data, especially in the area of data quality control, the combinatorial pattern and visualization of RNA modifications...Successful completion of the proposed project will lead to systematic prediction of the target genes of RNA methyltransferases and demethylases, the reconstruction of RNA methylation regulatory network, providing the RNA methylation research community with essential epitranscriptomic gene regulatory circuits and key computation tools.

随着高通量测序技术的发展特别是MeRIP-Seq技术的问世， RNA表观遗传学获得了更多的关注。近期的研究结果表明，RNA的6-甲基腺膘呤修饰m6A参与调控细胞分化、RNA剪切和蛋白质翻译等重要功能。..在丰富前期工作的基础上，本项目力图进一步完善针对RNA甲基化测序组学数据的生物信息学方法和工具，包括：MeRIP-Seq和RNA BS-Seq数据的质量控制和误差校正、更具统计效力的差异甲基化分析模型、RNA修饰的可视化方法以及不同种修饰的组合模式等等。本项目的核心内容重点关注RNA甲基化谱的调控手段，拟利用非参量贝叶斯网络生成模型系统重建RNA甲基化修饰位点受相关酶基因调控的网络机制，并进一步探索该系统调控机制在肝炎等疾病治疗和药物靶点筛选中的可能应用。..本项目的顺利实施将为RNA甲基化相关领域的研究项目提供关键的表观转录层面基因调控网路信息以及一系列针对RNA修饰组学数据的有效工具。

项目的背景: 随着高通量测序技术的发展特别是MeRIP-Seq技术的问世， RNA表观遗传学获得了更多的 关注。近期的研究结果表明，RNA的6-甲基腺膘呤修饰m6A参与调控细胞分化、RNA剪切和蛋白 质翻译等重要功能。.主要研究内容: 本项目进一步完善了针对RNA甲基化测序组学数据的生物信息学方法和工具，包括：MeRIP-Seq和RNA BS-Seq数据的质量控制和误差校正、更具统计效力 的差异甲基化分析模型、RNA修饰的可视化方法以及不同种修饰的组合模式等等。本项目的核 心内容重点关注RNA甲基化谱的调控手段，利用非参量贝叶斯网络生成模型系统重建RNA甲基 化修饰位点受相关酶基因调控的网络机制，并进一步探索了该系统调控机制在肝炎等疾病治疗和 药物靶点筛选中的可能应用。.重要结果: 课题组前后发表28篇科研论文，包括23篇SCI论文和5篇EI论文，包括6篇一区论文。开发了多个RNA修饰组学数据库和分析工具。 .关键数据: 研究项目主要关注方法学内容，大多采用来自NCBI的公开数据 .科学意义: 本项目为RNA甲基化相关领域的研究项目提供了关键的表观转录层面基因调控 网路信息以及一系列针对RNA修饰组学数据的有效工具。