Model Info:

Title:

Reduction of a biochemical model with preservation of its basic dynamic properties

Brief Description:

Membrane current and its application to conduction and excitation in nerve

Authors:

Sune Dano1, Mads F. Madsen1, Henning Schmidt2 and Gunnar Cedersund2

Affiliations:

1Department of Medical Biochemistry and Genetics, University of Copenhagen, Copenhagen, Denmark 2Fraunhofer Chalmers Research Centre for Industrial Mathematics, Gothenburg, Sweden

Abstract:

The complexity of full-scale metabolic models is a major obstacle for their effective use in computational systems biology. The aim of model reduction is to circumvent this problem by eliminating parts of a model, which are unimportant for the properties of interest. The choice of reduction method is influenced both by the type of model complexity, and by the objective with the reduction; therefore no single method is superior in all cases. In this work we present a comparative study of two different methods applied to a 20-dimensional model of yeast glycolytic oscillations. Our objective is to obtain biochemically meaningful reduced models, which reproduce the dynamic properties of the 20-dimensional model. The first method uses lumping and subsequent constrained parameter optimisation. The second method is a novel approach which eliminates variables, that are not essential for the dynamics. The applications of the two methods result in models of eight (lumping), six (elimination), and three (lumping followed by elimination) dimensions. All models have similar dynamical properties, and pin-point the same interactions as being crucial for the generation of the oscillations. The advantage of the novel method is that it is algorithmic, and does not require input in the form of biochemical knowledge. The lumping approach, on the other hand, is better at preserving biochemical properties, as we show through extensive analyses of the models.

Journal:

None