Oscillation patterns in negative feedback loops
Oscillation patterns in negative feedback loops
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DOI：
10.1073/pnas.0610759104
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发表时间：
2007-04-17
影响因子：
11.1
通讯作者：
Jensen, Mogens H.
中科院分区：
文献类型：
--
作者：
Pigolotti, Simone;Krishna, Sandeep;Jensen, Mogens H.
生物体具有调节系统，这些调节系统表现出各种各样的动力学行为，从简单的稳定稳态到开关和多稳态，再到振荡。早期的研究表明，蛋白质浓度或基因表达水平的振荡与调控网络中至少一个负反馈环的存在有关。在这里，我们研究一个非常一般的负反馈回路类的动力学。我们的主要结果是，当一个单一的负反馈回路占主导地位的动力学行为，浓度的最大值和最小值的序列表现出一种模式，唯一识别的循环的相互作用。这使我们能够设计一种算法来（i）测试观察到的振荡时间序列是否与单个潜在的负反馈回路一致，如果是，（ii）重建回路的精确结构，即，每种相互作用的激活/抑制性质。即使数据集中缺少某些变量，或者时间序列显示出瞬态（如阻尼振荡），该方法也适用。我们举例说明了我们的方法的相关性和有效性的限制与三个例子：p53-Mdm 2振荡，在蓝藻的昼夜节律基因的表达，并在雌激素敏感的pS2启动子的辅助因子的循环结合。
Organisms are equipped with regulatory systems that display a variety of dynamical behavior ranging from simple stable steady states, to switching and multistability, to oscillations. Earlier work has shown that oscillations in protein concentrations or gene expression levels are related to the presence of at least one negative feedback loop in the regulatory network. Here, we study the dynamics of a very general class of negative feedback loops. Our main result is that, when a single negative feedback loop dominates the dynamical behavior, the sequence of maxima and minima of the concentrations exhibit a pattern that uniquely identifies the interactions of the loop. This allows us to devise an algorithm to (i) test whether observed oscillating time series are consistent with a single underlying negative feedback loop, and if so, (ii) reconstruct the precise structure of the loop, i.e., the activating/repressing nature of each interaction. This method applies even when some variables are missing from the data set, or if the time series shows transients, like damped oscillations. We illustrate the relevance and the limits of validity of our method with three examples: p53-Mdm2 oscillations, circadian gene expression in cyanobacteria, and cyclic binding of cofactors at the estrogen-sensitive pS2 promoter.