Blossey Ralf, Cardelli Luca, Phillips Andrew
HFSP J. 2008 Feb;2(1):17-28. doi: 10.2976/1.2804749. Epub 2007 Nov 14.
We present an approach for constructing dynamic models for the simulation of gene regulatory networks from simple computational elements. Each element is called a "gene gate" and defines an inputoutput relationship corresponding to the binding and production of transcription factors. The proposed reaction kinetics of the gene gates can be mapped onto stochastic processes and the standard ordinary differential equation (ODE) description. While the ODE approach requires fixing the system's topology before its correct implementation, expressing them in stochastic pi-calculus leads to a fully compositional scheme: network elements become autonomous and only the inputoutput relationships fix their wiring. The modularity of our approach allows to pass easily from a basic first-level description to refined models which capture more details of the biological system. As an illustrative application we present the stochastic repressilator, an artificial cellular clock, which oscillates readily without any cooperative effects.
我们提出了一种从简单计算元件构建用于模拟基因调控网络的动态模型的方法。每个元件称为一个“基因门”,并定义了与转录因子的结合和产生相对应的输入输出关系。所提出的基因门反应动力学可以映射到随机过程和标准常微分方程(ODE)描述上。虽然ODE方法在正确实现之前需要固定系统拓扑,但用随机π演算来表达它们会产生一个完全组合式的方案:网络元件变得自主,只有输入输出关系确定它们的连接方式。我们方法的模块化允许轻松地从基本的一级描述过渡到捕捉生物系统更多细节的精细模型。作为一个说明性应用,我们展示了随机阻遏振荡子,一种人工细胞时钟,它在没有任何协同效应的情况下就能轻松振荡。