Noise propagation and signaling sensitivity in biological networks: a role for positive feedback.
Noise propagation and signaling sensitivity in biological networks: a role for positive feedback.
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DOI：
10.1371/journal.pcbi.0040008
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发表时间：
2008-01
影响因子：
4.3
通讯作者：
Barkai N
中科院分区：
文献类型：
--
作者：
Hornung G;Barkai N
基因和蛋白质之间的相互作用对于有效处理内部或外部信号至关重要，但这种连通性也通过在组件之间传播噪声而放大了随机波动。线性（无分支）级联显示出对输入信号变化的敏感性和缓冲噪声的能力之间的相互作用。我们寻找能够在保持信号敏感性的同时最小化噪声传播的生物电路，重点关注噪声以快速波动为特征的情况。负反馈可以缓冲这种类型的噪声，但这种缓冲是以更大程度上降低信号灵敏度为代价的。通过系统地分析三分量电路，我们确定正反馈作为一个中心主题，允许传播噪声的缓冲，同时保持对输入信号长期变化的灵敏度。我们分析地表明，在正反馈的存在下，噪声的降低来自于对快速波动随时间的平均的改进，并详细讨论了酵母中营养稳态控制的一种特殊实现。由于生物网络的设计针对多个约束条件进行了优化，因此可以使用正反馈来提高灵敏度，而不会损害缓冲传播噪声的能力。生物电路需要对环境信号的变化敏感，但同时又要缓冲可能施加在输入上的快速波动（噪声）。在本文中，我们分析了信号灵敏度和缓冲噪声能力之间的相互作用。先前的研究报告称，负反馈可以减弱噪音。然而，我们表明，这种能力是以更大幅度的灵敏度降低为代价的。事实上，当比较具有相同灵敏度的系统时，具有负反馈的系统比没有负反馈的系统更容易受到噪声的影响。我们寻找能够在保持高灵敏度的同时缓冲噪声的小型生物电路，并发现正反馈具有这种特性。这种正反馈缓冲噪声的能力反映了其缓慢的动态。我们讨论了作为噪声过滤装置的正反馈功能的一般要求，并描述了在酵母营养稳态中起作用的一种特殊实现。我们的研究强调在分析生物网络的设计逻辑时需要考虑多个约束。
Interactions between genes and proteins are crucial for efficient processing of internal or external signals, but this connectivity also amplifies stochastic fluctuations by propagating noise between components. Linear (unbranched) cascades were shown to exhibit an interplay between the sensitivity to changes in input signals and the ability to buffer noise. We searched for biological circuits that can maintain signaling sensitivity while minimizing noise propagation, focusing on cases where the noise is characterized by rapid fluctuations. Negative feedback can buffer this type of noise, but this buffering comes at the expense of an even greater reduction in signaling sensitivity. By systematically analyzing three-component circuits, we identify positive feedback as a central motif allowing for the buffering of propagated noise while maintaining sensitivity to long-term changes in input signals. We show analytically that noise reduction in the presence of positive feedback results from improved averaging of rapid fluctuations over time, and discuss in detail a particular implementation in the control of nutrient homeostasis in yeast. As the design of biological networks optimizes for multiple constraints, positive feedback can be used to improve sensitivity without a compromise in the ability to buffer propagated noise. Biological circuits need to be sensitive to changes in environmental signals but at the same time buffer rapid fluctuations (noise) that might be imposed on this input. In this paper, we analyze the interplay between sensitivity to signals and the ability to buffer noise. Previous studies reported that negative feedback attenuates noise. We show, however, that this ability comes at the expense of an even more dramatic reduction in sensitivity. In fact, when comparing systems of the same sensitivity, a system with negative feedback is more amenable to noise than a system without such feedback. We searched for small biological circuits that can buffer noise while maintaining high sensitivity, and found that positive feedback exhibits this property. This ability of positive feedback to buffer noise reflects its slowed-down dynamics. We discuss general requirements for the function of positive feedback as a noise-filtering device and describe a particular implementation that appears to function in yeast nutrient homeostasis. Our study emphasizes the need to consider multiple constraints when analyzing the design logic of biological networks.
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影响因子：
64.8
作者：
Becskei, A;Serrano, L
通讯作者：
Serrano, L
影响因子：
9.9
作者：
Dublanche, Yann;Michalodimitrakis, Konstantinos;Serrano, Luis
通讯作者：
Serrano, Luis
影响因子：
64.8
作者：
Austin, DW;Allen, MS;Simpson, ML
通讯作者：
Simpson, ML
DOI：
10.1073/pnas.162041399
发表时间：
2002-10-01
影响因子：
11.1
作者：
Swain, PS;Elowitz, MB;Siggia, ED
通讯作者：
Siggia, ED
DOI：
10.1073/pnas.0408507102
发表时间：
2005-03-08
影响因子：
11.1
作者：
Hooshangi, S;Thiberge, S;Weiss, R
通讯作者：
Weiss, R