Model reduction and analysis of robustness for the Wnt/beta-catenin signal transduction pathway

Abstract

We present a framework for model reduction of signal transduction networks. The methods are explained by considering a recent model for Wnt/beta-catenin signalling which plays an important regulatory role in cell development and oncogenesis. The procedure results in a reduction of system variables and parameters while maintaining the ability of the model to describe experimental data and to predict the in-vivo behaviour of the pathway. Using metabolic control analysis we quantified the response of the pathway towards random fluctuations of model parameters. This allows to characterise the robustness of the pathway against perturbations in stimulated and unstimulated states. We show that robustness depends on structural as well as kinetic properties of the pathway.