QSB: Computational and Experimental Studies of Pathways in Yeast

该项目的长期目标是研究一个框架，可以提高对复杂生物途径的拓扑/连通性的理解。本研究将实验分子遗传学与计算系统生物学相结合，开发了真核细胞中复杂信号转导通路的新方法。研究的初始系统是出芽酵母酿酒酵母的Ras和Tor通路。该研究将使用全基因组表达分析的数据集来开发和验证通路图。研究将侧重于三个分析途径，其目标是：(1)研究一种遗传上位分析方法，利用大量DNA微阵列数据定义路径的定性连通性图；(2)研究一种基于上层结构表示和混合整数线性优化框架的计算系统新方法，用于预测复杂路径的拓扑结构；(3)研究模型不确定性对代谢路径网络拓扑结构影响的定量分析框架。

The long range goal of this project is to investigate a framework that can improve understanding of the topology/connectivity of complex biological pathways. This research combines experimental molecular genetics with computational systems biology to develop new approaches for mapping complex signal transduction pathways in eukaryotic cells. The initial system for study is the Ras and Tor pathways in the budding yeast Saccharomyces cerevisiae. The research will employ data sets from whole genome expression analysis to develop and validate the pathway map. The research will focus on three avenues of analysis with the objectives: (1) to study a genetic epistasis analysis approach using extensive DNA microarray data to define a qualitative connectivity map of the pathways, (2) investigate a new computational systems approach based on a superstructure representation and a mixed integer linear optimization framework for the prediction of the topology of the complex pathways, and (3) study a quantitative analysis framework for the effect of model uncertainty on the network topology of the metabolic pathways.