A structured approach for the engineering of biochemical network models, illustrated for signalling pathways
A structured approach for the engineering of biochemical network models, illustrated for signalling pathways
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DOI：
10.1093/bib/bbn026
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发表时间：
2008-09-01
影响因子：
9.5
通讯作者：
Orton, Richard
中科院分区：
文献类型：
--
作者：
Breitling, Rainer;Gilbert, David;Orton, Richard
生化网络（信号转导级联、代谢途径、基因调控回路）的定量模型是现代系统生物学的核心组成部分。构建和管理这些复杂的模型是一项重大挑战，可以从理论计算科学采用的形式化方法的应用中受益。在这里，我们提供了一个一般性的介绍正式建模，强调直观的生化基础的建模过程中，但也可以为观众在计算科学和/或模型工程的背景。我们展示了如何信号转导级联可以在一个模块化的方式建模，使用定性的方法定性Petri网，和定量的方法连续Petri网和常微分方程（ODE）。我们回顾了细胞信号模型的主要基本构建模块，讨论了在模型构建过程中必须做出的关键设计决策，并提出了一些新的计算工具，可以帮助以简单直观的方式探索替代模块化模型。这些工具，这是基于Petri网理论，提供了方便的方式组成层次ODE模型，并允许定性分析其行为。我们用信号转导作为主要例子来说明中心概念。最终的目的是介绍一个通用的方法，提供了一个结构化的正式工程的生化网络的大规模模型的基础。
Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also accessible for an audience with a background in computing science and/or model engineering. We show how signal transduction cascades can be modelled in a modular fashion, using both a qualitative approachqualitative Petri nets, and quantitative approachescontinuous Petri nets and ordinary differential equations (ODEs). We review the major elementary building blocks of a cellular signalling model, discuss which critical design decisions have to be made during model building, and present a number of novel computational tools that can help to explore alternative modular models in an easy and intuitive manner. These tools, which are based on Petri net theory, offer convenient ways of composing hierarchical ODE models, and permit a qualitative analysis of their behaviour. We illustrate the central concepts using signal transduction as our main example. The ultimate aim is to introduce a general approach that provides the foundations for a structured formal engineering of large-scale models of biochemical networks.