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Biochemical Systems Theory: A Review

DOI: 10.1155/2013/897658

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Abstract:

Biochemical systems theory (BST) is the foundation for a set of analytical andmodeling tools that facilitate the analysis of dynamic biological systems. This paper depicts major developments in BST up to the current state of the art in 2012. It discusses its rationale, describes the typical strategies and methods of designing, diagnosing, analyzing, and utilizing BST models, and reviews areas of application. The paper is intended as a guide for investigators entering the fascinating field of biological systems analysis and as a resource for practitioners and experts. 1. Preamble Biochemical systems theory (BST) is a mathematical and computational framework for analyzing and simulating systems. It was originally developed for biochemical pathways but by now has become much more widely applied to systems throughout biology and beyond. BST is called “canonical,” which means that model construction, diagnosis, and analysis follow stringent rules, which will be discussed throughout this paper. The key ingredient of BST is the power-law representation of all processes in a system. BST has been the focus of a number of books [1–6], including some in Chinese and Japanese [7–9]. The most detailed modern text dedicated specifically to BST is [3]. Moreover, since its inception, numerous reviews have portrayed the evolving state of the art in BST. Most of these reviews summarized methodological advances for the analysis of biochemical pathway systems [10–50]. Others compared BST models with alternative modeling frameworks [32, 51–63]; some of these comparisons will be discussed later. Yet other reviews focused on specialty areas, such as customized methods for optimizing BST models (e.g., [64–67]) or estimating their parameters (e.g., [68–72]), strategies for discovering design and operating principles in natural system (e.g., [73–78]), and even the use of BST models in statistics [79–81]. A historical account of the first twenty years of BST was presented in [82]. Supporting the methodological developments in the field, several software packages were developed for different aspects of BST analysis. The earliest was ESSYNS [83–85], which supported all standard steady-state analyses and also contained a numerical solver that, at the time, was many times faster than any off-the-shelf software [86, 87]; see also [88]. Utilizing advances in computing and an extension of the solver from ESSYNS, Ferreira created the very user-friendly package PLAS, which is openly available and still very widely used [89] (see also [3]). Yamada and colleagues developed software to

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