From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli.
From qualitative data to quantitative models: analysis of the phage shock protein stress response in Escherichia coli.
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DOI：
10.1186/1752-0509-5-69
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发表时间：
2011-05-12
影响因子：
--
通讯作者：
Stumpf MP
中科院分区：
文献类型：
--
作者：
Toni T;Jovanovic G;Huvet M;Buck M;Stumpf MP
细菌已经进化出一套丰富的机制来感知和适应环境中的不利条件。这些对于它们的生存至关重要，这需要它们对细胞外应激反应，如热休克，乙醇处理或噬菌体感染。在这里，我们专注于研究噬菌体休克蛋白（Psp）的压力反应在大肠杆菌诱导的噬菌体感染或其他损害的细菌膜。这个系统还没有被理论建模或计算机分析。我们开发了一个模型的Psp响应系统，并说明如何可以构建和分析这些模型，以产生新的生物学假说，其动力学行为的稀疏和定性的信息。我们分析这个模型使用的工具，从Petri网理论和研究其动态范围是一致的，目前可用的知识，通过条件模型参数的可用数据在一个近似贝叶斯计算（ABC）框架。在这种ABC方法中，我们分析随机和确定性动力学。这种分析使我们能够识别不同类型的行为，这些机制的见解反过来可以用来设计新的，更详细的和时间分辨的实验。我们已经开发了第一个机制模型的Psp反应在E。杆菌这个模型使我们能够预测可能的定性随机和确定性的动态行为的关键分子的球员在压力反应。我们的推理方法可以应用到压力反应和信号系统更普遍：在ABC框架中，我们可以条件的数学模型的定性数据，以划定例如参数范围或定性系统动态的终点或定性信息。
Bacteria have evolved a rich set of mechanisms for sensing and adapting to adverse conditions in their environment. These are crucial for their survival, which requires them to react to extracellular stresses such as heat shock, ethanol treatment or phage infection. Here we focus on studying the phage shock protein (Psp) stress response in Escherichia coli induced by a phage infection or other damage to the bacterial membrane. This system has not yet been theoretically modelled or analysed in silico. We develop a model of the Psp response system, and illustrate how such models can be constructed and analyzed in light of available sparse and qualitative information in order to generate novel biological hypotheses about their dynamical behaviour. We analyze this model using tools from Petri-net theory and study its dynamical range that is consistent with currently available knowledge by conditioning model parameters on the available data in an approximate Bayesian computation (ABC) framework. Within this ABC approach we analyze stochastic and deterministic dynamics. This analysis allows us to identify different types of behaviour and these mechanistic insights can in turn be used to design new, more detailed and time-resolved experiments. We have developed the first mechanistic model of the Psp response in E. coli. This model allows us to predict the possible qualitative stochastic and deterministic dynamic behaviours of key molecular players in the stress response. Our inferential approach can be applied to stress response and signalling systems more generally: in the ABC framework we can condition mathematical models on qualitative data in order to delimit e.g. parameter ranges or the qualitative system dynamics in light of available end-point or qualitative information.
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DOI：
10.1126/stke.3442006re6
发表时间：
2006-07-18
期刊：
Science's STKE : signal transduction knowledge environment
影响因子：
--
作者：
Hlavacek, William S;Faeder, James R;Fontana, Walter
通讯作者：
Fontana, Walter
影响因子：
1.6
作者：
Heiner, M;Koch, I;Will, R
通讯作者：
Will, R
影响因子：
3.6
作者：
Kobayashi, Ryuji;Suzuki, Toshiharu;Yoshida, Masasuke
通讯作者：
Yoshida, Masasuke
影响因子：
3.2
作者：
Jovanovic, G;Weiner, L;Model, P
通讯作者：
Model, P
影响因子：
3.9
作者：
Huvet, Maxime;Toni, Tina;Stumpf, Michael P. H.
通讯作者：
Stumpf, Michael P. H.