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Computation capacities of a broad class of signaling networks are higher than their communication capacities.
Physical Biology ( IF 2.0 ) Pub Date : 2019-09-11 , DOI: 10.1088/1478-3975/ab4345
Iman Habibi 1 , Effat S Emamian , Osvaldo Simeone , Ali Abdi
Affiliation  

Due to structural and functional abnormalities or genetic variations and mutations, there may be dysfunctional molecules within an intracellular signaling network that do not allow the network to correctly regulate its output molecules, such as transcription factors. This disruption in signaling interrupts normal cellular functions and may eventually develop some pathological conditions. In this paper, computation capacity of signaling networks is introduced as a fundamental limit on signaling capability and performance of such networks. In simple terms, the computation capacity measures the maximum number of computable inputs, that is, the maximum number of input values for which the correct functional output values can be recovered from the erroneous network outputs, when the network contains some dysfunctional molecules. This contrasts with the conventional communication capacity that measures instead the maximum number of input values that can be correctly distinguished based on the erroneous network outputs. The computation capacity is higher than the communication capacity whenever the network response function is not a one-to-one function of the input signals, and, unlike the communication capacity, it takes into account the input-output functional relationships of the network. By explicitly incorporating the effect of signaling errors that result in the network dysfunction, the computation capacity provides more information about the network and its malfunction. Two examples of signaling networks are considered in the paper, one regulating caspase3 and another regulating NFκB, for which computation and communication capacities are investigated. Higher computation capacities are observed for both networks. One biological implication of this finding is that signaling networks may have more 'capacity' than that specified by the conventional communication capacity metric. The effect of feedback is studied as well. In summary, this paper reports findings on a new fundamental feature of the signaling capability of cell signaling networks.

中文翻译:

种类繁多的信令网络的计算能力高于其通信能力。

由于结构和功能异常或遗传变异和突变,细胞内信号网络中可能存在功能失调的分子,这些分子无法使网络正确调节其输出分子,例如转录因子。信号传导的这种中断会中断正常的细胞功能,并可能最终发展出某些病理状况。本文将信令网络的计算能力作为对此类网络的信令能力和性能的基本限制进行介绍。简而言之,当网络包含一些功能失常的分子时,计算能力将测量可计算输入的最大数量,即,可以从错误的网络输出中恢复正确的功能输出值的最大输入值数量。这与常规通信容量形成对比,常规通信容量可替代地测量可基于错误网络输出正确区分的输入值的最大数量。每当网络响应功能不是输入信号的一对一功能时,计算能力就高于通信能力,并且与通信能力不同,计算能力考虑了网络的输入-输出功能关系。通过显式合并导致网络故障的信令错误的影响,计算能力可提供有关网络及其故障的更多信息。本文考虑了两个信号网络示例,一个是调节胱天蛋白酶3,另一个是调节NFκB,研究了它们的计算和通信能力。对于两个网络都观察到更高的计算能力。这一发现的生物学含义是,信令网络可能比常规通信容量量度所指定的具有更多的“容量”。还研究了反馈的影响。总而言之,本文报告了有关蜂窝信令网络信令能力的新基本特征的发现。
更新日期:2019-11-01
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