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A method for the generation of standardized qualitative dynamical systems of regulatory networks

机译:一种生成监管网络标准化定性动力系统的方法

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Background Modeling of molecular networks is necessary to understand their dynamical properties. While a wealth of information on molecular connectivity is available, there are still relatively few data regarding the precise stoichiometry and kinetics of the biochemical reactions underlying most molecular networks. This imbalance has limited the development of dynamical models of biological networks to a small number of well-characterized systems. To overcome this problem, we wanted to develop a methodology that would systematically create dynamical models of regulatory networks where the flow of information is known but the biochemical reactions are not. There are already diverse methodologies for modeling regulatory networks, but we aimed to create a method that could be completely standardized, i.e. independent of the network under study, so as to use it systematically. Results We developed a set of equations that can be used to translate the graph of any regulatory network into a continuous dynamical system. Furthermore, it is also possible to locate its stable steady states. The method is based on the construction of two dynamical systems for a given network, one discrete and one continuous. The stable steady states of the discrete system can be found analytically, so they are used to locate the stable steady states of the continuous system numerically. To provide an example of the applicability of the method, we used it to model the regulatory network controlling T helper cell differentiation. Conclusion The proposed equations have a form that permit any regulatory network to be translated into a continuous dynamical system, and also find its steady stable states. We showed that by applying the method to the T helper regulatory network it is possible to find its known states of activation, which correspond the molecular profiles observed in the precursor and effector cell types.
机译:分子网络的背景建模对于理解它们的动力学特性是必要的。尽管可以获得有关分子连通性的大量信息,但是有关大多数分子网络基础的生化反应的精确化学计量和动力学的数据仍然相对较少。这种不平衡将生物网络的动力学模型的开发限制在少数具有良好特征的系统上。为了克服这个问题,我们希望开发一种方法,该方法可以系统地创建监管网络的动态模型,在该模型中,信息流已知,但生化反应未知。已经有用于建模监管网络的多种方法,但是我们旨在创建一种可以完全标准化的方法,即独立于所研究的网络,以便系统地使用它。结果我们开发了一组方程式,可用于将任何调节网络的图转换为连续的动力学系统。此外,还可以定位其稳定的稳态。该方法基于给定网络的两个动力学系统的构建,一个是离散的,一个是连续的。可以通过分析找到离散系统的稳定稳态,因此将其用于数值定位连续系统的稳定稳态。为了提供该方法的适用性示例,我们使用它来建模控制T辅助细胞分化的调控网络。结论所提出的方程式的形式允许将任何调节网络转化为连续的动力学系统,并找到其稳态稳态。我们表明,通过将该方法应用于T辅助物调控网络,可以找到其已知的激活状态,该状态对应于在前体细胞和效应细胞类型中观察到的分子谱。

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