miRNA位点产生的具序列多样性特点的isomiR是非编码RNA(ncRNA)调控的一个重要环节，解析其异常调控模式及与其它RNA的关系，有助于揭示复杂疾病的发生发展机制。基于前期研究，本课题拟结合理论研究及实验验证探讨isomiR-lncRNA的cross-talk：①基于isomiR生物学特点，利用信息熵表征其表达和功能特征；②提取isomiR与lncRNA的表达、功能、进化/位置等相关特征，特别引入靶mRNA并用熵度量RNA间关系，利用加权熵综合多种因素并投影至相互作用网络，以筛选关键分子模块；③实例应用：基于该方法筛选胆囊癌关键RNA进行实验验证及功能研究，根据反馈结果进一步完善分析策略。本课题旨在揭示这两种长度迥异的ncRNA在基因调控网络中的cross-talk，指导筛选疾病发生中功能密切相关的RNA。本研究的实施将有助于认识ncRNA复杂精确的调控功能在疾病发生中的重要作用。

IsomiRs, generated from miRNA locus with characteristics of sequence diversity, have been concerned as a pivotal link in non-coding RNA (ncRNA) regulatory network, and analyzing their abnormal regulatory patterns and relationships with other RNAs contribute to revealing the occurrence and development mechanism of complex diseases. On the basis of previous studies, the project aims to explore cross-talk between isomiR and lncRNA by combining theoretical research and experimental validation: ①Information entropy is used to characterize expression and function of isomiRs based on their biological characteristics. ②Relevant features are extracted, including expression, function, evolution/position, etc. In particular, target mRNAs are involved, and the correlations among different RNAs are measured by entropy. These multiple correlations are integrated by weighted entropy and further projected to interaction network. Then, the crucial RNA modules are screened based on the network. ③Instance application: crucial RNA molecules in gallbladder carcinoma are selected based on above mentioned method, and they are experimentally validated and performed functional studies. The validated results are used to further improve the analysis strategy. We aim to reveal the cross-talk between the two kinds of ncRNAs with diverged lengths in the gene regulatory network, and the relevant results will further guide to screen RNAs with tight functional relationships in diseases. This project will contribute to understanding the crucial roles of ncRNAs with complex and precise regulatory function in development of diseases.