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Dynamic modeling of gene expression in prokaryotes: application to glucose-lactose diauxie in Escherichia coli

机译:基因表达在原核生物中的动态建模:在大肠杆菌中的葡萄糖-葡萄糖双糖的应用

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摘要

Coexpression of genes or, more generally, similarity in the expression profiles poses an unsurmountable obstacle to inferring the gene regulatory network (GRN) based solely on data from DNA microarray time series. Clustering of genes with similar expression profiles allows for a course-grained view of the GRN and a probabilistic determination of the connectivity among the clusters. We present a model for the temporal evolution of a gene cluster network which takes into account interactions of gene products with genes and, through a non-constant degradation rate, with other gene products. The number of model parameters is reduced by using polynomial functions to interpolate temporal data points. In this manner, the task of parameter estimation is reduced to a system of linear algebraic equations, thus making the computation time shorter by orders of magnitude. To eliminate irrelevant networks, we test each GRN for stability with respect to parameter variations, and impose restrictions on its behavior near the steady state. We apply our model and methods to DNA microarray time series’ data collected on Escherichia coli during glucose-lactose diauxie and infer the most probable cluster network for different phases of the experiment.Electronic supplementary materialThe online version of this article (doi:10.1007/s11693-011-9079-2) contains supplementary material, which is available to authorized users.
机译:基因的共表达,或更普遍地,表达谱的相似性,对仅基于DNA微阵列时间序列数据推断基因调控网络(GRN)构成了不可克服的障碍。具有相似表达谱的基因的聚类允许对GRN进行详细了解,并可以概率确定聚类之间的连通性。我们提出了一种基因簇网络的时间演化模型,该模型考虑了基因产物与基因的相互作用以及通过非恒定降解速率与其他基因产物的相互作用。通过使用多项式函数对时间数据点进行插值,减少了模型参数的数量。以这种方式,参数估计的任务被简化为线性代数方程组,从而使计算时间缩短了几个数量级。为了消除不相关的网络,我们测试了每个GRN相对于参数变化的稳定性,并对其在稳态附近的行为施加了限制。我们将我们的模型和方法应用于在葡萄糖-乳糖双糖期间在大肠杆菌中收集的DNA微阵列时间序列数据,并推断出该实验不同阶段最可能的簇网络。电子补充材料本文的在线版本(doi:10.1007 / s11693) -011-9079-2)包含补充材料,授权用户可以使用。

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