Research

A simplified method for power-law modelling of metabolic pathways from time-course data and steady-state flux profiles

Tomoya Kitayama^1* , Ayako Kinoshita^1* , Masahiro Sugimoto^1,2 , Yoichi Nakayama^1,3 and Masaru Tomita¹

¹  Institute of Advanced Bioscience, Keio University, Fujisawa, 252-8520, Japan

²  Department of Bioinformatics, Mitsubishi Space Software Co. Ltd., Amagasaki, Hyogo, 661-0001, Japan

³  Network Biology Research Centre, Articell Systems Corporation, Keio Fujisawa Innovation Village, 4489 Endo, Fujisawa, 252-0816, Japan

author email corresponding author email* Contributed equally

Theoretical Biology and Medical Modelling 2006, 3:24doi:10.1186/1742-4682-3-24

Published:	17 July 2006

Abstract

Background

In order to improve understanding of metabolic systems there have been attempts to construct S-system models from time courses. Conventionally, non-linear curve-fitting algorithms have been used for modelling, because of the non-linear properties of parameter estimation from time series. However, the huge iterative calculations required have hindered the development of large-scale metabolic pathway models. To solve this problem we propose a novel method involving power-law modelling of metabolic pathways from the Jacobian of the targeted system and the steady-state flux profiles by linearization of S-systems.

Results

The results of two case studies modelling a straight and a branched pathway, respectively, showed that our method reduced the number of unknown parameters needing to be estimated. The time-courses simulated by conventional kinetic models and those described by our method behaved similarly under a wide range of perturbations of metabolite concentrations.

Conclusion

The proposed method reduces calculation complexity and facilitates the construction of large-scale S-system models of metabolic pathways, realizing a practical application of reverse engineering of dynamic simulation models from the Jacobian of the targeted system and steady-state flux profiles.