title: Dynamic regulatory on/off minimization for biological systems under internal temporal perturbations.
abstract: BACKGROUND
  Flux balance analysis (FBA) together with its extension, dynamic FBA, have proven instrumental for analyzing the robustness and dynamics of metabolic networks by employing only the stoichiometry of the included reactions coupled with adequately chosen objective function. In addition, under the assumption of minimization of metabolic adjustment, dynamic FBA has recently been employed to analyze the transition between metabolic states.
  
  
  RESULTS
  Here, we propose a suite of novel methods for analyzing the dynamics of (internally perturbed) metabolic networks and for quantifying their robustness with limited knowledge of kinetic parameters. Following the biochemically meaningful premise that metabolite concentrations exhibit smooth temporal changes, the proposed methods rely on minimizing the significant fluctuations of metabolic profiles to predict the time-resolved metabolic state, characterized by both fluxes and concentrations. By conducting a comparative analysis with a kinetic model of the Calvin-Benson cycle and a model of plant carbohydrate metabolism, we demonstrate that the principle of regulatory on/off minimization coupled with dynamic FBA can accurately predict the changes in metabolic states.
  
  
  CONCLUSIONS
  Our methods outperform the existing dynamic FBA-based modeling alternatives, and could help in revealing the mechanisms for maintaining robustness of dynamic processes in metabolic networks over time.
authors.affiliation: Max-Planck Institute of Molecular Plant Physiology, Potsdam, Germany. kleessen@mpimp-golm.mpg.de
authors.forename: Sabrina
authors.initials: S
authors.lastname: Kleessen
authors.forename: Zoran
authors.initials: Z
authors.lastname: Nikoloski
mesh_terms: D050260:Carbohydrate Metabolism; D007700:Kinetics; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D010944:Plants / Q000378:metabolism; D049490:Systems Biology / Q000379:methods*; D013997:Time Factors