Autonomous Boolean modelling of developmental gene regulatory networks
Autonomous Boolean modelling of developmental gene regulatory networks
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DOI：
10.1098/rsif.2012.0574
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发表时间：
2013-01-06
影响因子：
3.9
通讯作者：
Socolar, Joshua E. S.
中科院分区：
文献类型：
--
作者：
Cheng, Xianrui;Sun, Mengyang;Socolar, Joshua E. S.
在早期胚胎发育期间，基因之间的调控相互作用网络动态地决定了分化组织的模式。我们证明了与交互相关的重要定时信息可以在自治布尔模型中忠实地表示，其中表示表达式水平的二进制变量在连续时间内被更新，并且这种模型可以提供对从常微分方程(ODE)模型中难以提取的特征的直接洞察。作为应用，我们对经过实验研究的控制苍蝇身体分割的网络进行了建模。该布尔模型成功地生成了在正常和遗传扰动的苍蝇胚胎中形成的模式，允许推导出对时延参数的约束，澄清了与不同ODE参数集相关联的逻辑，并为在参数空间中研究连通性和稳健性提供了平台。通过阐明调控时间延迟在模式形成中的作用，结果表明在早期胚胎发育中有新类型的实验测量。
During early embryonic development, a network of regulatory interactions among genes dynamically determines a pattern of differentiated tissues. We show that important timing information associated with the interactions can be faithfully represented in autonomous Boolean models in which binary variables representing expression levels are updated in continuous time, and that such models can provide a direct insight into features that are difficult to extract from ordinary differential equation (ODE) models. As an application, we model the experimentally well-studied network controlling fly body segmentation. The Boolean model successfully generates the patterns formed in normal and genetically perturbed fly embryos, permits the derivation of constraints on the time delay parameters, clarifies the logic associated with different ODE parameter sets and provides a platform for studying connectivity and robustness in parameter space. By elucidating the role of regulatory time delays in pattern formation, the results suggest new types of experimental measurements in early embryonic development.