Transactions on Computational Systems Biology XII
Transactions on Computational Systems Biology XII
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计算系统生物学汇刊 XII
DOI：
10.1007/978-3-642-11712-1_7
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Ciocchetta F
中科院分区：
文献类型：
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作者：
Ciocchetta F
在这项工作中，我们提出了一个Bio-PEPA模型描述核因子κB（NF-κB）信号通路。我们的模型特别关注NF-κB对外界刺激的动态反应。该途径中的每一种生物化学物质都由一个特定的Bio-PEPA组分来表示，外部刺激则由描述信号开始和结束的时间依赖性Bio-PEPA事件来抽象，Bio-PEPA模型是该途径的一种正式的中间表示，可以对该模型进行各种分析。随机和确定性模拟进行验证我们的模型对实验数据和in-silicoexperiments在文献中，并验证一些属性，如，外部刺激的持续时间和总NF-κB初始量对某些感兴趣的物种的行为的影响。此外，我们使用随机模拟来比较单个细胞的行为与细胞群体的平均行为。最后，敏感性分析被认为是调查的最有影响力的参数的模型。重要的是，所采取的方法表明，一些参数的敏感性随时间的演变的途径。
In this work we present a Bio-PEPA model describing the Nuclear FactorκB (NF-κB) signalling pathway. In particular our model focuses on the dynamic response of NF-κB to an external stimulus. Each biochemical species in the pathway is represented by a specific Bio-PEPA component and the external stimulus is abstracted by time-dependent Bio-PEPA events describing the start and the end of the signal.The Bio-PEPA model is a formal intermediate representation of the pathway on which various kinds of analysis can be performed. Both stochastic and deterministic simulations are carried out to validate our model against the experimental data andin-silicoexperiments in the literature and to verify some properties, such as, the impact of the duration of the external stimulus and of the total NF-κB initial amount on the behaviour of some species of interest. Furthermore we use stochastic simulation to compare the behaviour of the single cell against the average behaviour of a population of cells. Finally, sensitivity analysis is considered to investigate the most influential parameters of the model. Importantly, the approach taken suggests that the sensitivity of some parameters alters with the time evolution of the pathway.