(475f) Topological Metabolic Analysis for the Interrogation of Metabolic Networks

We introduce Topological Metabolic Analysis (TMA) a novel, flexible, optimization-based framework for computational modeling of metabolic networks. The framework is adapted from the Infinite-Dimensional-State-Space approach originally introduced by Manousiouthakis and co-workers for the representation of complex networks of heat- and mass-exchangers. We claim that our approach presents certain mathematical advantages as compared to the stoichiometric balancing techniques in common use, and that these advantages are primarily conferred through a rigorous mathematical treatment of network topology. We demonstrate the ability of our technique to probe network reconstructions for potentially missing functionality. We further demonstrate the technique's unique ability not only to fully describe the topology of a particular metabolic network, but to identify a finite number of alternate network topologies that are all each globally optimal with respect to a given objective. Because this modeling framework implicitly enforces the metabolite balances typically elucidated using costly C-13/NMR experiments, it presents an \emph{in silico} means of calculating the complete set of reaction activities within a network without the need for costly and laborious in vitro experimentation. Finally, we demonstrate the ability of our modeling approach to identify network solutions which simultaneously optimize a particular teleological objective while ensuring minimal deviation from empirically observed system behavior through the use of a novel ``hybrid" objective function.