Dynamic Analysis of Integrated Signaling, Metabolic, and Regulatory Networks

摘要: Extracellular cues affect signaling, metabolic, and regulatory processes to elicit cellular responses. Although intracellular networks are highly integrated, previous analyses have largely focused on independent (e.g., metabolism) without considering the interplay that exists among them. However, there is evidence many diseases arise from multifunctional components with roles throughout networks. Therefore, in this study, we propose a flux balance analysis (FBA)–based strategy, referred as integrated dynamic FBA (idFBA), dynamically simulates phenotypes arising The idFBA framework requires an stoichiometric reconstruction of processes. It assumes quasi-steady-state conditions for “fast” reactions incorporates “slow” into formalism time-delayed manner. To assess efficacy idFBA, developed prototypic system comprising network features characteristic actual systems incorporating kinetic parameters based typical time scales observed literature. was applied system, which evaluated different environments gene rules. In addition, similar manner representative module single-cell eukaryotic organism Saccharomyces cerevisiae. Ultimately, facilitated quantitative, systemic effects extracellular generated comparable time-course predictions when contrasted equivalent model. Since solves linear programming problem does not require exhaustive list detailed parameters, it may be efficiently scaled incorporate at genome scale, such S. cerevisiae presented here.