后基因组时代系统生物学吴家睿.pptVIP

Comparison with growth phenotypes showed that experimental and computational outcomes agreed in 10,828 (78.7%) Each case is categorized by comparison type (Exp/Met/Reg), high-throughput phenotyping array data (Exp) predictions for the E. coli network with regulatory constraints (Reg) predictions for the E. coli network ignoring such constraints (Met) Results are listed as ‘+’ (predicted or observed growth), ‘-’ (no growth) or ‘n’ (for cases involving a regulatory gene knockout not predictable by the Met model). a fraction of agreement (FA) between regulatory model predictions and observed phenotypes Knockout strains (FA0.60): uncharacterized metabolic or regulatory capabilities Updated on basis of new experimental data obtained (iMC1010v2) Comparison of the predicted and observed expression changes for the v1 and v2 models. A question mark indicates either that the given gene was not included in the model or that no expression data were obtained for a given shift Biological network elucidation by a model-centric approach If model predictions are consistent with experimental observations, network is adequately characterized. If not, model identifies a knowledge gap and may be used to update, validate and generate hypotheses about organism function. 系统生物学的学派 本体论： 关注事物的不同性质 方法论： 选择不同的研究策略 科学中存在着不同的研究学派 整体分析学派 （Global-analysis School） 系统生物学就是应用生物的、遗传的或化学的方法系统地干扰生物系统，检测所有相关基因、蛋白质和信号通路的反应，整合这些数据，并最终建立数学模型以描述系统的结构和对外部作用的反应。 —— L. Hood 整体分析学派的研究对象：完整的生物系统 整体分析学派的研究策略：组学 Genome Transcriptome Proteome Citric acid cycle Metabolome Predictive models of molecular machines involved in C. elegans early embryogenesis Nature, 2005, 436:861 三类实验数据的计算生物学整合 (by RNAi) 建立整合了三种数据的早期发育网络 661 EE genes 31,173 edges 0.9/node (Int) 5.0/node (Tr) 44/node (Ph) 早期发育网络的分析 (two or more types of links) Total 305 nodes (genes) with 1036 edges 实验检测未知基因的预期的位置 Embryonic localization patterns of GFP-tagged fusion proteins analysed by time-lapse microscopy are largely consistent with model pr