A method of `speed coefficients' for biochemical model reduction applied to the NF-B system

zbMATH Keywords

characteristic timescales fast-slow systems Krishna model model reduction nuclear factor kappa B parameter embedding perturbation theory signaling networks

Mathematics Subject Classification ID

Computational methods for problems pertaining to biology (92-08) Systems biology, networks (92C42)

Abstract: The relationship between components of biochemical network and the resulting dynamics of the overall system is a key focus of computational biology. However, as these networks and resulting mathematical models are inherently complex and non-linear, the understanding of this relationship becomes challenging. Among many approaches, model reduction methods provide an avenue to extract components responsible for the key dynamical features of the system. Unfortunately, these approaches often require intuition to apply. In this manuscript we propose a practical algorithm for the reduction of biochemical reaction systems using fast-slow asymptotics. This method allows the ranking of system variables according to how quickly they approach their momentary steady state, thus selecting the fastest for a steady state approximation. We applied this method to derive models of the Nuclear Factor kappa B network, a key regulator of the immune response that exhibits oscillatory dynamics. Analyses with respect to two specific solutions, which corresponded to different experimental conditions identified different components of the system that were responsible for the respective dynamics. This is an important demonstration of how reduction methods that provide approximations around a specific steady state, could be utilised in order to gain a better understanding of network topology in a broader context.

Review text

The authors propose an algorithm for the reduction of biochemical reaction systems, which does not rely on a intuition-based extraction of key regulatory components. This new approach is based on fast-slow asymptotics and uses the ranking on the approach of system variables at their momentary steady-state. First, the perturbation theory for fast-slow systems is presented. It is followed by a description of the parametric embedding used for the identification of small parameters. Next, a heuristic method for the identification of speed coefficients is described; the section concludes with a full description of the model reduction algorithm. The authors present the results of this approach on several examples including the minimal model of the NF-kB system, in response to continuous or pulsed \(\mathrm{TNF}\alpha\), and an application for the Krishna model.

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