Ensemble Modeling of Metabolic Networks

Complete modeling of metabolic networks is desirable, but it is difficult to accomplish because of the lack of kinetics. As a step toward this goal, we have developed an approach to build an ensemble of dynamic models that reach the same steady state. The models in the ensemble are based on the same...

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Bibliographic Details
Published in:Biophysical journal 2008-12, Vol.95 (12), p.5606-5617
Main Authors: Tran, Linh M., Rizk, Matthew L., Liao, James C.
Format: Article
Language:English
Subjects:
Biophysical Theory and Modeling
Construction
Control
Enzymes
Kinetics
Mathematical models
Metabolic Networks and Pathways
Metabolism
Models, Biological
Molecular chemistry
Networks
Perturbation methods
Reaction kinetics
Steady state
Thermodynamics
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Summary:Complete modeling of metabolic networks is desirable, but it is difficult to accomplish because of the lack of kinetics. As a step toward this goal, we have developed an approach to build an ensemble of dynamic models that reach the same steady state. The models in the ensemble are based on the same mechanistic framework at the elementary reaction level, including known regulations, and span the space of all kinetics allowable by thermodynamics. This ensemble allows for the examination of possible phenotypes of the network upon perturbations, such as changes in enzyme expression levels. The size of the ensemble is reduced by acquiring data for such perturbation phenotypes. If the mechanistic framework is approximately accurate, the ensemble converges to a smaller set of models and becomes more predictive. This approach bypasses the need for detailed characterization of kinetic parameters and arrives at a set of models that describes relevant phenotypes upon enzyme perturbations.
ISSN:0006-3495
1542-0086
DOI:10.1529/biophysj.108.135442