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酵母细胞周期蛋白基因网络的虚拟突变揭示了转录控制网络的复杂动态。

Virtual mutagenesis of the yeast cyclins genetic network reveals complex dynamics of transcriptional control networks.

机构信息

Laboratory of Bioinformatics, Institute of Microbiology ASCR v.v.i., Prague, Czech Republic.

出版信息

PLoS One. 2011 Apr 25;6(4):e18827. doi: 10.1371/journal.pone.0018827.

DOI:10.1371/journal.pone.0018827
PMID:21541341
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3081828/
Abstract

Study of genetic networks has moved from qualitative description of interactions between regulators and regulated genes to the analysis of the interaction dynamics. This paper focuses on the analysis of dynamics of one particular network--the yeast cyclins network. Using a dedicated mathematical model of gene expression and a procedure for computation of the parameters of the model from experimental data, a complete numerical model of the dynamics of the cyclins genetic network was attained. The model allowed for performing virtual experiments on the network and observing their influence on the expression dynamics of the genes downstream in the regulatory cascade. Results show that when the network structure is more complicated, and the regulatory interactions are indirect, results of gene deletion are highly unpredictable. As a consequence of quantitative behavior of the genes and their connections within the network, causal relationship between a regulator and target gene may not be discovered by gene deletion. Without including the dynamics of the system into the network, its functional properties cannot be studied and interpreted correctly.

摘要

基因网络的研究已经从调控因子和受调控基因之间相互作用的定性描述发展到了相互作用动态的分析。本文的重点是分析一个特定的网络——酵母细胞周期蛋白网络的动态。使用专门的基因表达数学模型和从实验数据计算模型参数的过程,我们获得了细胞周期蛋白遗传网络动态的完整数值模型。该模型允许在网络上进行虚拟实验,并观察它们对调控级联下游基因表达动态的影响。结果表明,当网络结构更加复杂,调控相互作用是间接的时,基因缺失的结果是高度不可预测的。由于基因及其在网络中的连接的定量行为,调控因子和靶基因之间的因果关系可能不会通过基因缺失来发现。如果不将系统的动态纳入网络,就无法正确地研究和解释其功能特性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/238643979650/pone.0018827.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/3f65405600f5/pone.0018827.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/2e90eeb5d135/pone.0018827.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/5156091dafcf/pone.0018827.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/4e33eddb2e05/pone.0018827.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/f0051a6270fd/pone.0018827.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/238643979650/pone.0018827.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/3f65405600f5/pone.0018827.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/2e90eeb5d135/pone.0018827.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/5156091dafcf/pone.0018827.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/4e33eddb2e05/pone.0018827.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/f0051a6270fd/pone.0018827.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4b4b/3081828/238643979650/pone.0018827.g006.jpg

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本文引用的文献

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Comparative study of three commonly used continuous deterministic methods for modeling gene regulation networks.三种常用于基因调控网络建模的连续确定性方法的比较研究。
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