Constaint-Based Modeling of Metabolic Networks.ppt

* Alternative Optima The optimal FBA solution is not unique growth growth growth One solution Optimal solutions Near-optimal solutions Basic solutions enumeration – MILP (Lee, et. al, 2000) Flux variability analysis (Mahadevan, et. al. 2003) Hit and run sampling (Almaas, et. al, 2004) Uniform random sampling (Wiback, et. al, 2004) 黎饱申脑乎御宋碎寸冲跺肥呵洼伪佃忘锤性复伴费薛箍座傲尿光瀑隙斌熄Constraint-Based Modeling of Metabolic NetworksConstraint-Based Modeling of Metabolic Networks * What Do Multiple Solutions Represent ? Some of the solutions probably do not represent biologically meaningful metabolic behaviors as there are missing constraints Previous studies tackled this problem by: Incorporating additional constraints: regulatory constraints (Covert, et. al., 2004) Looking for reactions for which new constraints may significantly reduce the solution space (Wiback, et. al., 2004) FBA solution space Meaningful solutions 苇蜂咳种企棠胚却菲砷蛾后推舜嘻懂砖豌已兆笔宪凋饿自厕耿轧涌坐顽凶Constraint-Based Modeling of Metabolic NetworksConstraint-Based Modeling of Metabolic Networks * Interpretations of Metabolic Space Effect of exogenous factors – the metabolic space corresponds to growth in a medium under various external conditions that are beyond the model’s scope such as stress or temperature Heterogeneity within a population - the metabolic space represents heterogenous metabolic behaviors by individuals within a cell population (Mahadevan, et. al., 2003, Price, et. al., 2004) Alternative evolutionary paths – the metabolic space represents different metabolic states attainable through different evolutionary paths (Mahadevan, et. al., 2003, Fong, et. al., 2004) The three interpretations are obviously not mutually exclusive 讨渴怎竭搂湾棕婉龟覆孕札疯延披鸦纱宰娩转古繁翰肮黔望袍蚀势喊察滴Constraint-Based Modeling of Metabolic NetworksConstraint-Based Modeling of Metabolic Networks * Alternative Optima: Basic Solutions Enumeration Lee, et. al, 2000 Basic solutions – metabolic states with minimal numbe