Application of a novel optimization-based approach to characterize integrated signalling, regulatory, and metabolic biochemical networks

Extracellular cues affect signaling, metabolic, and regulatory processes to elicit cellular responses. Although intracellular signaling, metabolic, and regulatory networks are highly integrated, previous analyses have largely focused on independent processes (e.g., metabolism) without considering the interplay that exists among them. In this paper, we present the recent development of a flux balance analysis (FBA)-based strategy, referred to as integrated dynamic FBA (idFBA), that dynamically simulates cellular phenotypes arising from integrated networks [Lee et al., 2007]. The idFBA framework solves a linear program to find the optimal fluxes of biochemical reactions in an integrated network. It assumes quasi-steady-state conditions for “fast” reactions and incorporates “slow” reactions into the stoichiometric relationships to confine the feasible solution space. We also describe its recent application to a prototypic integrated system to assess the efficacy of idFBA [Lee et al., 2007].