Abstract

Complex models of biochemical reaction systems have become increasingly common in the systems biology literature. The complexity of such models can present a number of obstacles for their practical use, often making problems difficult to intuit or computationally intractable. Methods of model reduction can be employed to alleviate the issue of complexity by seeking to eliminate those portions of a reaction network that have little or no effect upon the outcomes of interest, hence yielding simplified systems that retain an accurate predictive capacity. This review paper seeks to provide a brief overview of a range of such methods and their application in the context of biochemical reaction network models. To achieve this, we provide a brief mathematical account of the main methods including timescale exploitation approaches, reduction via sensitivity analysis, optimisation methods, lumping, and singular value decomposition-based approaches. Methods are reviewed in the context of large-scale systems biology type models, and future areas of research are briefly discussed.

Highlights

  • Model complexity can be used to refer to a number of specific properties of mathematical models occurring in a range of scientific contexts

  • Model reduction has a long history in the mathematical modelling of biological systems; perhaps the most famous example is Briggs and Haldane’s application of the quasi-steady-state approximation (QSSA) for the simplification of a model of the enzyme–substrate reaction (Briggs and Haldane 1925)

  • Coordinate transforming model reduction methods can often be applied with good results to models for which an exploitable, singularly perturbed form is not readily available

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Summary

Introduction

Model complexity can be used to refer to a number of specific properties of mathematical models occurring in a range of scientific contexts. Model reduction has a long history in the mathematical modelling of biological systems; perhaps the most famous example is Briggs and Haldane’s application of the quasi-steady-state approximation (QSSA) for the simplification of a model of the enzyme–substrate reaction (Briggs and Haldane 1925). They demonstrated that a simplifying assumption could take the unsolvable, nonlinear, four-dimensional system of coupled ordinary differential equations (ODEs) that constituted the model, to a single ODE whilst still providing an accurate description of the dynamics for a wide range of possible parameterisations

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