Translating biochemical network models between different kinetic formats.
Mechanistic biochemical network models describe the dynamics of intracellular metabolite pools in terms of substance concentrations, stoichiometry and reaction kinetics. Data from stimulus response experiments are currently the most informative source for in-vivo parameter estimation in such models. However, only a part of the parameters of classical enzyme kinetic models can usually be estimated from typical stimulus response data. For this reason, several alternative kinetic formats using different "languages" (e.g. linear, power laws, linlog, generic and convenience) have been proposed to reduce the model complexity. The present contribution takes a rigorous "multi-lingual" approach to data evaluation by translating biochemical network models from one kinetic format into another. For this purpose, a new high-performance algorithm has been developed and tested. Starting with a given model, it replaces as many kinetic terms as possible by alternative expressions while still reproducing the experimental data. Application of the algorithm to a published model for Escherichia coli's sugar metabolism demonstrates the power of the new method. It is shown that model translation is a powerful tool to investigate the information content of stimulus response data and the predictive power of models. Moreover, the local and global approximation capabilities of the models are elucidated and some pitfalls of traditional single model approaches to data evaluation are revealed.
Hadlich
Frieder
F
Department of Simulation, Institute of Systems Engineering, University of Siegen, Germany. frieder.hadlich@uni-siegen.de
Noack
Stephan
S
Wiechert
Wolfgang
W
D000465:Algorithms; D003198:Computer Simulation; D016247:Information Storage and Retrieval / Q000379:methods; D007700:Kinetics; D055442:Metabolome / Q000502:physiology*; D008954:Models, Biological; D009097:Multienzyme Complexes / Q000378:metabolism*; D016571:Neural Networks, Computer; D015398:Signal Transduction / Q000502:physiology*
D009097:Multienzyme Complexes