PNNL

Abstract

The partitioning of biological networks into coupled functional modules is gaining increasing attention in the biological sciences. 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, 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, we apply a system theoretical analysis approach to derive the causal input-output relationships of the functional module for the human epidermal growth factor receptor (HER) mediated Erk and Akt signaling pathways. Using a library of cell lines expressing varying levels of EGFR and HER2, we show that a transfer function-based representation can be successfully applied to quantitatively characterize information transfer in this system.