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Boolean Network Approach to Negative Feedback Loops of the p53 Pathways: Synchronized Dynamics and Stochastic Limit Cycles

机译:p53通路负反馈环的布尔网络方法:   同步动力学和随机极限环

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摘要

Deterministic and stochastic Boolean network models are build for thedynamics of negative feedback loops of the p53 pathways. It is shown that themain function of the negative feedback in the p53 pathways is to keep p53 at alow steady state level, and each sequence of protein states in the negativefeedback loops, is globally attracted to a closed cycle of the p53 dynamicsafter being perturbed by outside signal (e.g. DNA damage). Our theoretical andnumerical studies show that both the biological stationary state and thebiological oscillation after being perturbed are stable for a wide range ofnoise level. Applying the mathematical circulation theory of Markov chains, weinvestigate their stochastic synchronized dynamics and by comparing the networkdynamics of the stochastic model with its corresponding deterministic networkcounterpart, a dominant circulation in the stochastic model is the naturalgeneralization of the deterministic limit cycle in the deterministic system.Moreover, the period of the main peak in the power spectrum, which is in commonuse to characterize the synchronized dynamics, perfectly corresponds to thenumber of states in the main cycle with dominant circulation. Such a largeseparation in the magnitude of the circulations, between a dominant, main cycleand the rest, gives rise to the stochastic synchronization phenomenon.
机译:确定性和随机布尔网络模型是为p53途径的负反馈回路的动力学建立的。结果表明,p53途径中负反馈的主要功能是将p53保持在较低的稳态水平,而负反馈回路中的每个蛋白质状态序列在受到外界干扰后都被吸引到p53动力学的封闭循环中。信号(例如DNA损伤)。我们的理论和数值研究表明,扰动后的生物稳态和生物振荡在很宽的噪声水平下都是稳定的。应用马尔可夫链的数学循环理论,我们研究了它们的随机同步动力学,并通过将随机模型的网络动力学与其对应的确定性网络对等进行比较,随机模型中的主导循环是确定性系统中确定性极限环的自然概括。功率谱中主峰的周期(通常用来表征同步动力学)完全对应于具有主循环的主循环中的状态数。在主要的主循环和其余的循环之间,循环量的如此大的间隔引起了随机同步现象。

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    Ge, Hao; Qian, Min;

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  • 年度 2009
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