融合多组学数据优化筛选恶性肿瘤中表观失调非编码RNA及其功能研究

项目名称： 融合多组学数据优化筛选恶性肿瘤中表观失调非编码RNA及其功能研究

项目编号： No.61502126

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 计算机科学学科

项目作者： 李永生

作者单位： 哈尔滨医科大学

项目金额： 21万元

中文摘要： 恶性肿瘤的发生发展是遗传与表观遗传共同驱动的结果。系统鉴定识别恶性肿瘤发生发展过程中表观失调的非编码RNA (noncoding RNA, ncRNA)并探讨其介导的调控网络在恶性肿瘤中的作用机制是具有挑战意义的课题。本课题将以恶性肿瘤中ncRNA不同层面的组学资源为起点，开发计算学方法鉴定恶性肿瘤发生发展过程中表观失调的ncRNA，进一步构建表观失调ncRNA介导的转录和转录后调控网络，归纳总结已知恶性肿瘤相关ncRNA的拓扑结构以及调控规律，开发恶性肿瘤相关ncRNA诊断、预后标记优先化方法，进一步基于表观失调ncRNA介导的转录和转录后失调靶基因预测ncRNA生物标记的分子功能，最后利用分子生物学实验证实表观失调ncRNA的调控作用以及分子功能，形成以ncRNA为核心的复杂分析系统，建立查询、计算及分析的一体化平台，为恶性肿瘤及其进展发病机制的理解提供新的视角和新的思路。

中文关键词： 表观遗传学；生物信息分析；生物分子网络；新一代测序技术；系统生物学

英文摘要： The development of human cancer is driven by changes in the genetic and epigenetic landscape of the cell. However, identification and functional analysis of epigenetically dysregulated noncoding RNAs (ncRNAs) and integration of different types of genomic datasets to discover the regulatory networks mediated by ncRNAs are challenging. This application describes the development of computational methods and integrative genomic strategies for systematically dissecting the the epigenetically dysregulated ncRNA in cancer, and a combination of computational and experimental approaches to unravel several important functional networks mediated by ncRNA in multiple types of cancer. Specifically, it will (i) develop a computational method to interrogate ncRNA methylation, histone modification and expression in tumor and normal samples and utilize an integrative genomic strategy to identify epigenetically dysregualted ncRNAs, (ii) identify the transcriptional and post-transcriptional regulatory networks mediated by ncRNAs and summarize the regulatory principles of known cancer related ncRNAs, and integration of the principles to discover the ncRNA biomarkers for the diagnosis, treatment and prognosis of human cancer, (iii) predict the functions of ncRNAs based on the regulatory targets and validate the function of ncRNAs and the regulatory relationship using experimental approaches. In addition to its scientific proposal, this application develops cutting-edge computational methods, and uses a combination of computational and experimental approaches to understand the upstream mechanism of ncRNAs expression dysregulation and the downstream regulatory networks mediated by ncRNAs in cancer. The results obtained by this application will be a highly valuable resource for investigations at understanding epigenetic regulation of cancer and identification of epigenetic-based therapeutic targets.

英文关键词： epigenetics;bioinformatic analysis;biological network;next generation sequencing;system biology