基于系统发育谱的细菌sRNA靶标发现及注释研究

Bacterial sRNAs are a class of small regulatory RNAs of about 40~500nt in length. By bingding to their target mRNAs or proteins, bacterial sRNAs play an important role in a variety of biological processes such as bacterial virulence, quorum sensing, sensing the enviromental changes and even tolerance. Therefore, identification of sRNA targets is very important for sRNA functional studies. By using the idea of co-evolution and the methods of phylogenetic profile and hierarchical clustering, we intend to present a new strategy for identification of bacterial sRNA targets. Additionally, we will also construct an comprehensive platform for sRNA function annotation, pathway analysis and comparative genomics study using many kinds of data available publicly. Ultimately, this project will provide valuable bioinformatics support for identification and validation of sRNA targets, and will also promote the progress of bacterial sRNAs studies.

细菌sRNA是一类长度在40~500个核苷酸的调控小RNA，主要通过与靶标mRNA结合对靶基因表达进行转录后调控或直接与靶标蛋白结合调控靶标蛋白的活性，从而影响细菌的毒力基因表达、群体感应、环境压力应答乃至耐药性。因此，识别细菌sRNA靶标对阐明细菌sRNA功能具有重要意义。本项目拟基于进化共存的思想，综合运用系统发育谱、层次聚类等技术，尝试提出一种全新的细菌sRNA靶标发现方法并进行实验验证。此外，还将结合多套数据，构建综合性的sRNA功能分析平台，从而对细菌sRNA靶标进行功能注释、作用通路分析以及比较基因组学研究。本项目的开展，将为实验发现细菌sRNA靶标并鉴定其功能提供高效的生物信息学支持，有助于加快细菌sRNA相关研究的进程。

在该课题资助下，根据项目研究内容，开展了四个方面研究：①建立了基于系统发育谱矩阵与聚类算法的大肠杆菌sRNA靶标预测流程；②开发了细菌sRNA靶标数据库sRNATarBase3.0及sRNA功能在线注释系统(http://ccb1.bmi.ac.cn/srnatarbase/)；③基于RNA-Seq 技术发现了福氏志贺菌新sRNA，并对其致病机制进行研究；④基于系统发育谱的人lncRNA功能注释研究。这些研究为细菌sRNA或人lncRNA功能注释提供了很好的生物信息学支持。