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System theoretical investigation of human epidermal growth factor receptor-mediated signalling

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4 Author(s)
Y. Zhang ; Pacific Northwest National Laboratory ; H. Shankaran ; L. Opresko ; H. Resat

The partitioning of biological networks into coupled-functional modules is being increasingly applied for developing predictive models of biological systems. This approach has the advantage that predicting a system-level response does not require a mechanistic description of the internal dynamics of each module. Identification of the input-output characteristics of the network modules and the connectivity between the modules provide the necessary quantitative representation of system dynamics. However, the determination of the input-output relationships of the modules is not trivial; it requires the controlled perturbation of module inputs and systematic analysis of experimental data. In this report, the authors apply a system theoretical analysis approach to derive the time-dependent input-output relationships of the functional module for the human epidermal growth factor receptor (HER) mediated Erk and Akt signalling pathways. Using a library of cell lines expressing endogenous levels of epidermal growth factor receptor (EGFR) and varying levels of HER2, the authors show that a transfer function-based representation can be successfully applied to quantitatively characterise information transfer in this system.

Published in:

IET Systems Biology  (Volume:2 ,  Issue: 5 )