Guaranteed error bounds for structured complexity reduction of biochemical networks

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• 作者：Thomas P. Prescott^a ; ^b ; ^{thomas.prescott@dtc.ox.ac.uk} ; Antonis Papachristodoulou^b ; ^c
• 关键词：Model reduction ; Systems biology ; Mathematical biology ; Singular perturbation
• 刊名：Journal of Theoretical Biology
• 出版年：2012
• 期刊代码：79_00225193
• 类别：mt
• 出版时间：7 July, 2012
• 卷：304
• 期：Complete
• 页码：172-182
• 文件大小：386 K

摘要

Biological systems are typically modelled by nonlinear differential equations. In an effort to produce high fidelity representations of the underlying phenomena, these models are usually of high dimension and involve multiple temporal and spatial scales. However, this complexity and associated stiffness makes numerical simulation difficult and mathematical analysis impossible. In order to understand the functionality of these systems, these models are usually approximated by lower dimensional descriptions. These can be analysed and simulated more easily, and the reduced description also simplifies the parameter space of the model. This model reduction inevitably introduces error: the accuracy of the conclusions one makes about the system, based on reduced models, depends heavily on the error introduced in the reduction process.

In this paper we propose a method to calculate the error associated with a model reduction algorithm, using ideas from dynamical systems. We first define an error system, whose output is the error between observables of the original and reduced systems. We then use convex optimisation techniques in order to find approximations to the error as a function of the initial conditions. In particular, we use the Sum of Squares decomposition of polynomials in order to compute an upper bound on the worst-case error between the original and reduced systems. We give biological examples to illustrate the theory, which leads us to a discussion about how these techniques can be used to model-reduce large, structured models typical of systems biology.