Virginia Bioinformatics Institute, Virginia Tech, Washington Street, MC 0477, Blacksburg, VA 24061, USA.
BMC Bioinformatics. 2011 Jul 20;12:295. doi: 10.1186/1471-2105-12-295.
Many biological systems are modeled qualitatively with discrete models, such as probabilistic Boolean networks, logical models, Petri nets, and agent-based models, to gain a better understanding of them. The computational complexity to analyze the complete dynamics of these models grows exponentially in the number of variables, which impedes working with complex models. There exist software tools to analyze discrete models, but they either lack the algorithmic functionality to analyze complex models deterministically or they are inaccessible to many users as they require understanding the underlying algorithm and implementation, do not have a graphical user interface, or are hard to install. Efficient analysis methods that are accessible to modelers and easy to use are needed.
We propose a method for efficiently identifying attractors and introduce the web-based tool Analysis of Dynamic Algebraic Models (ADAM), which provides this and other analysis methods for discrete models. ADAM converts several discrete model types automatically into polynomial dynamical systems and analyzes their dynamics using tools from computer algebra. Specifically, we propose a method to identify attractors of a discrete model that is equivalent to solving a system of polynomial equations, a long-studied problem in computer algebra. Based on extensive experimentation with both discrete models arising in systems biology and randomly generated networks, we found that the algebraic algorithms presented in this manuscript are fast for systems with the structure maintained by most biological systems, namely sparseness and robustness. For a large set of published complex discrete models, ADAM identified the attractors in less than one second.
Discrete modeling techniques are a useful tool for analyzing complex biological systems and there is a need in the biological community for accessible efficient analysis tools. ADAM provides analysis methods based on mathematical algorithms as a web-based tool for several different input formats, and it makes analysis of complex models accessible to a larger community, as it is platform independent as a web-service and does not require understanding of the underlying mathematics.
许多生物系统都是用离散模型进行定性建模的,例如概率布尔网络、逻辑模型、Petri 网和基于代理的模型,以便更好地理解它们。分析这些模型的完整动态的计算复杂度随变量数量呈指数增长,这阻碍了对复杂模型的处理。存在用于分析离散模型的软件工具,但它们要么缺乏确定性分析复杂模型的算法功能,要么由于需要理解底层算法和实现、没有图形用户界面或难以安装而对许多用户不可用。需要高效的、易于使用的、易于建模人员使用的分析方法。
我们提出了一种有效识别吸引子的方法,并引入了基于网络的动态代数模型分析工具(ADAM),该工具为离散模型提供了这种方法和其他分析方法。ADAM 将几种离散模型类型自动转换为多项式动力系统,并使用计算机代数工具分析它们的动态。具体来说,我们提出了一种识别离散模型吸引子的方法,该方法等效于求解系统的多项式方程,这是计算机代数中一个长期研究的问题。通过对系统生物学中出现的离散模型和随机生成的网络进行广泛的实验,我们发现本文提出的代数算法对于大多数生物系统所维持的结构的系统来说是快速的,即稀疏性和鲁棒性。对于一组大型已发表的复杂离散模型,ADAM 在不到一秒的时间内就确定了吸引子。
离散建模技术是分析复杂生物系统的有用工具,生物学界需要易于使用的高效分析工具。ADAM 作为一种基于网络的工具,提供了基于数学算法的分析方法,适用于几种不同的输入格式,并且由于它是作为网络服务独立于平台的,并且不需要理解底层数学,因此使更广泛的社区能够进行分析复杂模型。