Towards a genome-scale kinetic model of cellular metabolism

Abstract

Background: Advances in bioinformatic techniques and analyses have led to the availability of genome-scale metabolic reconstructions. The size and complexity of such networks often means that their potential behaviour can only be analysed with constraint-based methods. Whilst requiring minimal experimental data, such methods are unable to give insight into cellular substrate concentrations. Instead, the long-term goal of systems biology is to use kinetic modelling to characterize fully the mechanics of each enzymatic reaction, and to combine such knowledge to predict system behaviour.

Results: We describe a method for building a parameterized genome-scale kinetic model of a metabolic network. Simplified linlog kinetics are used and the parameters are extracted from a kinetic model repository. We demonstrate our methodology by applying it to yeast metabolism. The resultant model has 956 metabolic reactions involving 820 metabolites, and, whilst approximative, has considerably broader remit than any existing models of its type. Control analysis is used to identify key steps within the system.

Conclusions: Our modelling framework may be considered a stepping-stone toward the long-term goal of a fully-parameterized model of yeast metabolism. The model is available in SBML format from the BioModels database (BioModels ID: MODEL1001200000) and at http://www.mcisb.org/resources/genomescale/.

Figure 1

An example of the SBML model's MIRIAM-compliant annotations. The (concentration) parameter is taken from BioModels ID 70. Since the parameter is not available from yeast, it is flagged as originating from taxonomy 9606 (H. Sapiens).