Algebraic dependency models of protein signal transduction networks from time-series data

Abstract

Signal transduction networks are crucial for inter- and intra-cellular signaling. Signals are often transmitted via covalent modification of protein structure, with phosphorylation/dephosphorylation as the primary example. In this paper, we apply a recently described method of computational algebra to the modeling of signaling networks, based on time-course protein modification data. Computational algebraic techniques are employed to construct next-state functions. A Monte Carlo method is used to approximate the Deegan–Packel Index of Power corresponding to the respective variables. The Deegan–Packel Index of Power is used to conjecture dependencies in the cellular signaling networks. We apply this method to two examples of protein modification time-course data available in the literature. These experiments identified protein carbonylation upon exposure of cells to sub-lethal concentrations of copper. We demonstrate that this method can identify protein dependencies that might correspond to regulatory mechanisms to shut down glycolysis in a reverse, step-wise fashion in response to copper-induced oxidative stress in yeast. These examples show that the computational algebra approach can identify dependencies that may outline signaling networks involved in the response of glycolytic enzymes to the oxidative stress caused by copper.