Laboratoire TIMC-IMAG, UMR CNRS/UJF 5525, Domaine de la Merci, 38710 La Tronche, France.
BMC Bioinformatics. 2010 Jul 20;11:385. doi: 10.1186/1471-2105-11-385.
A growing demand for tools to assist the building and analysis of biological networks exists in systems biology. We argue that the use of a formal approach is relevant and applicable to address questions raised by biologists about such networks. The behaviour of these systems being complex, it is essential to exploit efficiently every bit of experimental information. In our approach, both the evolution rules and the partial knowledge about the structure and the behaviour of the network are formalized using a common constraint-based language.
In this article our formal and declarative approach is applied to three biological applications. The software environment that we developed allows to specifically address each application through a new class of biologically relevant queries. We show that we can describe easily and in a formal manner the partial knowledge about a genetic network. Moreover we show that this environment, based on a constraint algorithmic approach, offers a wide variety of functionalities, going beyond simple simulations, such as proof of consistency, model revision, prediction of properties, search for minimal models relatively to specified criteria.
The formal approach proposed here deeply changes the way to proceed in the exploration of genetic and biochemical networks, first by avoiding the usual trial-and-error procedure, and second by placing the emphasis on sets of solutions, rather than a single solution arbitrarily chosen among many others. Last, the constraint approach promotes an integration of model and experimental data in a single framework.
系统生物学中对构建和分析生物网络工具的需求不断增长。我们认为,使用正式方法对于解决生物学家提出的有关这些网络的问题是相关且适用的。由于这些系统的行为复杂,因此必须有效地利用每一条实验信息。在我们的方法中,使用通用的基于约束的语言对进化规则和网络结构和行为的部分知识进行形式化。
在本文中,我们的形式化和声明式方法应用于三个生物学应用。我们开发的软件环境允许通过一类新的生物学相关查询专门解决每个应用程序。我们表明,我们可以轻松地以正式的方式描述遗传网络的部分知识。此外,我们表明,这种基于约束算法方法的环境提供了各种功能,不仅限于简单的模拟,例如一致性证明、模型修订、属性预测、相对于指定标准的最小模型搜索。
这里提出的形式化方法从根本上改变了探索遗传和生化网络的方式,首先通过避免常见的试错过程,其次通过强调解决方案集,而不是在许多其他解决方案中任意选择单个解决方案。最后,约束方法促进了模型和实验数据在单个框架中的集成。