Model reduction and analysis of robustness for the Wnt/beta-catenin signal transduction pathway.
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.
Krüger
Roland
R
Theoretical Biophysics, Institute of Biology, Humboldt University Berlin, Invalidenstr. 42, Berlin 10115, Germany. roland.krueger@rz.hu-berlin.de
Heinrich
Reinhart
R
D000818:Animals; D002471:Cell Transformation, Neoplastic; D003598:Cytoskeletal Proteins / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology*; D007700:Kinetics; D008433:Mathematics; D008954:Models, Biological; D015398:Signal Transduction / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology*; D051153:Wnt Proteins; D014981:Xenopus; D029867:Xenopus Proteins; D051176:beta Catenin
C495266:CTNNB1 protein, Xenopus; C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D036341:Intercellular Signaling Peptides and Proteins; D015534:Trans-Activators; D051153:Wnt Proteins; D029867:Xenopus Proteins; D051176:beta Catenin