Orrell David, Ramsey Stephen, de Atauri Pedro, Bolouri Hamid
Institute for Systems Biology 1441 North 34th Street, Seattle, WA 98103, USA.
Bioinformatics. 2005 Jan 15;21(2):208-17. doi: 10.1093/bioinformatics/bth479. Epub 2004 Aug 19.
Genetic regulatory networks are often affected by stochastic noise, due to the low number of molecules taking part in certain reactions. The networks can be simulated using stochastic techniques that model each reaction as a stochastic event. As models become increasingly large and sophisticated, however, the solution time can become excessive; particularly if one wishes to determine the effect on noise of changes to a series of parameters, or the model structure. Methods are therefore required to rapidly estimate stochastic noise.
This paper presents an algorithm, based on error growth techniques from non-linear dynamics, to rapidly estimate the noise characteristics of genetic networks of arbitrary size. The method can also be used to determine analytical solutions for simple sub-systems. It is demonstrated on a number of cases, including a prototype model of the galactose regulatory pathway in yeast.
A software tool which incorporates the algorithm is available for use as part of the stochastic simulation package Dizzy. It is available for download at http://labs.systemsbiology.net/bolouri/software/Dizzy/
A conceptual model of the regulatory part of the galactose utilization pathway in yeast, used as an example in the paper, is available at http://labs.systemsbiology.net/bolouri/models/galconcept.dizzy
由于参与某些反应的分子数量较少,基因调控网络常常受到随机噪声的影响。可以使用将每个反应建模为随机事件的随机技术来模拟这些网络。然而,随着模型变得越来越大且复杂,求解时间可能会变得过长;特别是当人们想要确定一系列参数变化或模型结构变化对噪声的影响时。因此,需要一些方法来快速估计随机噪声。
本文提出了一种基于非线性动力学中误差增长技术的算法,用于快速估计任意规模基因网络的噪声特征。该方法还可用于确定简单子系统的解析解。在多个案例中进行了演示,包括酵母中半乳糖调控途径的一个原型模型。
一个包含该算法的软件工具可作为随机模拟软件包Dizzy的一部分使用。可从http://labs.systemsbiology.net/bolouri/software/Dizzy/下载。
本文中用作示例的酵母半乳糖利用途径调控部分的概念模型可从http://labs.systemsbiology.net/bolouri/models/galconcept.dizzy获取。