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从实验数据的时间斜率信息中解析细胞网络的功能相互作用结构。

Unravelling the functional interaction structure of a cellular network from temporal slope information of experimental data.

作者信息

Cho Kwang-Hyun, Shin Sung-Young, Choo Sang-Mok

机构信息

College of Medicine, Seoul National University, Jongno-gu, Seoul, Korea.

出版信息

FEBS J. 2005 Aug;272(15):3950-9. doi: 10.1111/j.1742-4658.2005.04815.x.

Abstract

Due to the unavoidable nonbiological variations accompanying many experiments, it is imperative to consider a way of unravelling the functional interaction structure of a cellular network (e.g. signalling cascades or gene networks) by using the qualitative information of time-series experimental data instead of computation through the measured absolute values. In this spirit, we propose a very simple but effective method of identifying the functional interaction structure of a cellular network based on temporal ascending or descending slope information from given time-series measurements. From this method, we can gain insight into the acceptable measurement error ranges in order to estimate the correct functional interaction structure and we can also find guidance for a new experimental design to complement the insufficient information of a given experimental dataset. We developed experimental sign equations, making use of the temporal slope sign information from time-series experimental data, without a specific assumption on parameter perturbations for each network node. Based on these equations, we further describe the available specific information from each part of experimental data in detail and show the functional interaction structure obtained by integrating such information. In this procedure, we use only simple algebra on sign changes without complicated computations on the measured absolute values of the experimental data. The result is, however, verified through rigorous mathematical definitions and proofs. The present method provides us with information about the acceptable measurement error ranges for correct estimation of the functional interaction structure and it further leads to a new experimental design to complement the given experimental data by informing us about additional specific sampling points to be chosen for further required information.

摘要

由于许多实验中不可避免地存在非生物学变异,因此必须考虑一种方法,即通过使用时间序列实验数据的定性信息,而非通过测量绝对值进行计算,来揭示细胞网络(如信号级联或基因网络)的功能相互作用结构。本着这种精神,我们提出了一种非常简单但有效的方法,用于基于给定时间序列测量的时间上升或下降斜率信息来识别细胞网络的功能相互作用结构。通过这种方法,我们可以深入了解可接受的测量误差范围,以便估计正确的功能相互作用结构,并且我们还可以为新的实验设计找到指导,以补充给定实验数据集的不足信息。我们利用时间序列实验数据的时间斜率符号信息,开发了实验符号方程,而无需对每个网络节点的参数扰动进行特定假设。基于这些方程,我们进一步详细描述了来自实验数据各部分的可用特定信息,并展示了通过整合此类信息获得的功能相互作用结构。在此过程中,我们仅对符号变化使用简单代数,而不对实验数据的测量绝对值进行复杂计算。然而,结果通过严格的数学定义和证明得到了验证。本方法为我们提供了关于正确估计功能相互作用结构的可接受测量误差范围的信息,并且通过告知我们为获取进一步所需信息而要选择的额外特定采样点,进一步引导我们进行新的实验设计以补充给定的实验数据。

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