miRNA调控复杂疾病相关蛋白质互作网络的研究

The purpose of the project is to construct and study miRNA regulatory cardiovascular and cerebrovascular diseases associated human protein-protein interaction networks. We construct miRNA target protein-relevent protein interaction network, miRNA-relevent protein bidirection network, miRNA/disease gene-relevent protein birection network. Based on the information from gene expression profiles, Gene ontology and KEGG pathway database, a novel method is proposed and used to construct dynamic protein interaction network (DPIN). The characteristics of disease-related proteins and other proteins are researched based on the graph theory. A novel feature with global and local information of network is proposed and used to identify disease-related potential protein based on the machine learning method of supported vector machine, random forest, etc. On the basis of bionic optimization algorithm, a comparison algorithm with heuristic properties is presented and utilized to compare the protein interaction network. Proteins, protein complexes, pairs of protein-protein interaction and function modules, which play key roles in the occurrence and development of cardiovascular and cerebrovascular disease, are recognized by using the proposed comparison algorithm for protein interaction networks contained in different time points. The studies of molecular docking and homology modeling, combined with electrochemistry and other analytical method, are performed to provide potential targets for drug research. The project will not only help the understanding of the pathogenesis of the cardiovascular and cerebrovascular disease, but also help the finding of the drug target. In addition, it also has an important theoretical significance and practical value in the diagnosis and treatment of the cardiovascular and cerebrovascular disease.

本项目以miRNA调控人类心脑血管疾病相关蛋白质互作网络的构建与分析为研究目标。构建miRNA靶蛋白质-相关蛋白质互作网络，miRNA-相关蛋白质双向网络，miRNA/疾病基因-相关蛋白质双向网络。基于基因表达谱和基因本体论等注释信息，构建动态蛋白质互作网络。建立全局和局部网络拓扑结构特征的描述符，结合建模技术，研究与疾病相关的潜在蛋白质预测模型。建立基于仿生优化算法的蛋白质互作网络比对算法。通过对不同时间点上的心脑血管细胞内蛋白质互作网络的比对，发现重要的蛋白质，蛋白质复合物，蛋白质相互作用对，以及功能模块。采用分子对接和同源模建等技术，并结合电分析化学和其它分析方法，为疾病的治疗提供潜在靶标。本项目的研究不仅有助于从系统和全局角度理解蛋白质之间的相互作用对参与的重要信号转导和生物调控路径等信息，而且有助于心脑血管疾病的防治、临床诊断和致病机理等研究，具有重要的理论意义和实际应用价值。

本项目以miRNA调控人类心脑血管疾病相关蛋白质互作网络的构建与分析为研究目标。构建miRNA靶蛋白质-相关蛋白质互作网络，miRNA-相关蛋白质双向网络，miRNA/疾病基因-相关蛋白质双向网络。基于基因表达谱和基因本体论等注释信息，构建动态蛋白质互作网络。建立全局和局部网络拓扑结构特征的描述符，结合建模技术，研究与疾病相关的潜在蛋白质预测模型。建立基于仿生优化算法的蛋白质互作网络比对算法。通过对不同时间点上的心脑血管细胞内蛋白质互作网络的比对，发现重要的蛋白质，蛋白质复合物，蛋白质相互作用对，以及功能模块。采用分子对接和同源模建等技术，并结合电分析化学和其它分析方法，为疾病的治疗提供潜在靶标。本项目的研究不仅有助于从系统和全局角度理解蛋白质之间的相互作用对参与的重要信号转导和生物调控路径等信息，而且有助于心脑血管疾病的防治、临床诊断和致病机理等研究，具有重要的理论意义和实际应用价值。