肿瘤预后与生物学通路的异常密切相关，同时，ncRNA通过协同调控介导了异常通路之间的crosstalk。此外，isoform水平表达增加了研究的精确性。本项目通过整合遗传效应以及通路内部结构与ncRNA介导的通路之间的交互作用，提出更有效的基于isoform水平识别肿瘤预后通路区域及标志物的研究方法，并开发应用性软件及分析平台。我们首先结合序列和表达水平识别肿瘤预后相关的ncRNA-isoform调控关系。其次，将通路重构成以isoform为节点的网络模型，整合预后相关ncRNA-isoform关系构建ncRNA介导的全局isoform网络来反应通路内部与通路之间的复杂关系。最后，考虑遗传效应的预后驱动作用，计算网络中isoform及ncRNA节点受预后信号经通路内部与通路间交互作用的影响程度，开发整合节点影响程度和表达预后相关性的测度，并应用于识别预后通路区域及ncRNA标志物的研究中。

The tumor prognosis is closely related with abnormal of biological pathways, and ncRNAs are involved in the abnormal pathway crosstalk through regulatory mechanism. Moreover, isoform level expression increases the research accuracy. This project plans to develop more effectively methods for identifying tumor prognostic pathway regions and signatures based on isoform level, applicability software and analysis platform through integrating genetic effect as well as pathway internal structure and ncRNA-mediated pathway crosstalk. First, we will identify tumor prognostic regulations between ncRNAs and isoforms based on sequence and expression information. Then, we reconstruct pathway into network model with isoform as node, and construct a ncRNA-mediated global isoform network by integrating the prognosis related ncRNA-isoform relationships. This global network can reflect the relationships in and between pathways. Finally, we will consider the driver roles of genetic effect, and calculate the influence extent of isoform and ncRNA nodes which is affected from the internal effect of pathway and pathway crosstalk. A strategy integrating the influence extent and expression relevance will be developed, and applied to identify the prognostic pathway regions and ncRNA signatures. This project is of great significance in clarifying the inherent correlation mechanism between malignant tumor prognosis and biological pathways, and identifying prognostic signatures.