旧药新用的系统生物学研究

项目名称： 旧药新用的系统生物学研究

项目编号： No.61304178

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 自动化技术、计算机技术

项目作者： 吴自凯

作者单位： 上海理工大学

项目金额： 24万元

中文摘要： 药物研发过程成本高但成功率不高，究其原因，生物是个复杂系统，很难全面准确地度量新药在体内引起的复杂效应。系统生物学用系统科学的观点研究生命科学，探求将已知用途的药物应用到治疗其它疾病的研究是目前的一个研究热点。本项目将利用优化方法集成不同尺度和层面的异源数据来对人体胞内系统进行建模，推断和比较疾病条件下和药物扰动条件下的活性子系统，构建药物功能关联网络，进行旧药新用的预测。在方法论研究中，我们将根据实际问题和数据结构的特点来建模，以保证复杂生物问题的简化以及求解算法的高效。本项目的研究不仅可以建立一个敏感而特异的旧药新用筛选鉴定平台，用来指导和补充旧药新用的生物医学实验，还可以推动优化理论、生物分子网络和数据集成的交叉研究，加快国内旧药新用研究这一新兴交叉学科的发展。

中文关键词： 旧药新用；药物敏感性预测；复杂网络模型；蛋白质结构预测；稀疏信号恢复

英文摘要： Many experimental drugs were given up during various research development phase or even withdrawn from market just because the compact effect, more importantly, side effect in human body brought out by drug administration were not captured accrately and comprehensively. Given this, repositioning existing drugs with known indications computationally becomes an hot topic in systems biology recently. In this project, we will integrate all available hetrougeneous data with various scale and level to model cellular sytems by sytems engineering methods，identify and compare active subsystems or subnetworks under disease condition and drug purtubation. Finally, drug funtional association network will be inferred and drugs with known indications repositioned. As to the methodlogy research, we will model cellular sytems or network based on various characteristic of various heterougeneous data with formula's simplicity and algorithm's efficient being taken into account. The goal of this project is to establish a platform for repositioning drug with high sensitivity and specificity, guide and complement the clinical efforts on repositoning drug, promote the interdisciplinary research among systems engineering, biomolecular network and data integration and accelerate the development of drug repositioning domestically.

英文关键词： drug repositioning；drug sensitivity prediction；complex network model；protein structure prediction；sparse signal recovery