癌症miRNA海绵因果网络与模块识别及其功能特性研究

Recent studies have discovered that miRNA sponges are closely associated with the occurrence and development of cancers, and it is a significant and challenging subject to study the mechanisms of miRNA sponges in cancers. From the perspective of systems biology, this subject integrates heterogeneous biological data including high throughput data, such as miRNA, lncRNA, mRNA, pseudogene and circRNA expression profiles, miRNA-target databases, and genes-disease relationship databases, to study the identification and reconfirmation of cancer miRNA sponges, the causal relationships between cancer miRNA sponges, and new methods and technologies of miRNA, lncRNA, mRNA, pseudogene and circRNA expression data analysis. The aim is to identify cancer-related miRNA sponges and miRNA sponge causal networks and modules in cancers, and further develop a bioinformatics analysis software package for inferring miRNA sponge causal networks and modules in cancers. By combining molecular function databases (GO, KEGG, etc.), we apply the methods into Pan-Cancer data analysis including 12 disease types to mine cancer-conserved and specific miRNA sponge causal networks and modules. The research results will be of great importance in exploring the pathogenesis mechanisms of cancers, and promoting the study on precision medicine of human cancers.

新近研究发现miRNA海绵与癌症发生发展密切相关，研究miRNA海绵在癌症疾病中的作用机制是具有挑战意义的课题。本课题从系统生物学的角度，整合异构生物数据：miRNA、lncRNA、mRNA、pseudogene和circRNA表达谱数据，miRNA靶标数据库，基因-疾病关系数据库，研究了癌症miRNA海绵识别与再确认，癌症miRNA海绵之间的因果关系，miRNA、lncRNA、mRNA、pseudogene和circRNA多重表达谱分析新方法和新技术，旨在识别癌症miRNA海绵以及miRNA海绵因果网络与模块，开发癌症miRNA海绵因果网络与模块识别的生物信息学分析软件包，并结合分子功能数据库（GO、KEGG等），应用方法于12种泛癌（Pan-Cancer）疾病的数据分析，挖掘出癌症保守和特异的miRNA海绵因果网络与模块，对探究癌症发病机制，以及推进人类癌症的精准医疗研究具有重要意义。

日益增长的证据表明miRNA海绵与癌症的发生发展密切相关，其复杂调控机制成为理解癌症发展机理的重要突破口。然而，癌症关联的miRNA海绵调控网络和模块及其功能特性研究仍处于初级阶段。本项目以miRNA海绵为核心，整合人类癌症异构数据源（表达谱数据，miRNA靶标数据，基因-疾病关系数据等），开发新方法（LncmiRSRN和LMSM）和新工具（miRspongeR），旨在识别癌症miRNA海绵以及miRNA海绵网络与模块，剖析其潜在的生物功能和临床生存预后关联；进一步，基于因果推理模型，提出新方法（hiddenICP，miRsyn和MSLCRN）挖掘非编码RNA（miRNA/lncRNA）因果调控关系，旨在识别miRNA海绵因果网络和模块，理解非编码RNA因果调控机制和辅助临床靶基因治疗；此外，为进一步拓展研究，提出新框架（miRReg和ASDmiR）识别法洛四联症和自闭症关联的miRNA海绵网络和模块，并以合作者的方式参与miRNA信息检索和名称转换工具（miRBaseConverter）开发和优化。本项目开展的系列研究工作，为整合识别人类癌症miRNA海绵网络与模块及解析miRNA海绵的功能特性提供新方法和新技术，为探究miRNA海绵在癌症发生发展中的功能机制以及推进miRNA海绵关联的临床诊断和治疗具有重要意义。