Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae.
Reconstruction and logical modeling of glucose repression signaling pathways in Saccharomyces cerevisiae.
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DOI：
10.1186/1752-0509-3-7
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发表时间：
2009-01-14
影响因子：
--
通讯作者：
Nielsen J
中科院分区：
文献类型：
--
作者：
Christensen TS;Oliveira AP;Nielsen J
在酿酒酵母中，高水平葡萄糖的存在导致一系列被称为葡萄糖阻遏的下调效应。由于存在反馈回路和不同路径之间的串扰，该过程是复杂的，使得使用直观方法来分析系统变得复杂。我们建立了酵母葡萄糖阻遏的逻辑模型，形式化为超图。该模型是基于验证的调控相互作用构建的，它包括50个基因转录本，22个蛋白质，5个代谢产物和118个超边。我们计算了网络中所有节点的逻辑稳态，以模拟野生型和缺失突变体对不同糖可用性的反应。通过比较基因节点的逻辑状态与转录组数据的变化来评估模型的预测能力。总体而言，我们观察到71%的真实预测，并分析了其余预测的错误和差异来源。虽然逻辑（布尔）模型的二进制性质带来了固有的局限性，我们的模型构成了一个主要的工具，用于存储监管知识，搜索假设中的不一致性，并评估删除参与葡萄糖抑制的调控元件的影响。
In the yeast Saccharomyces cerevisiae, the presence of high levels of glucose leads to an array of down-regulatory effects known as glucose repression. This process is complex due to the presence of feedback loops and crosstalk between different pathways, complicating the use of intuitive approaches to analyze the system. We established a logical model of yeast glucose repression, formalized as a hypergraph. The model was constructed based on verified regulatory interactions and it includes 50 gene transcripts, 22 proteins, 5 metabolites and 118 hyperedges. We computed the logical steady states of all nodes in the network in order to simulate wildtype and deletion mutant responses to different sugar availabilities. Evaluation of the model predictive power was achieved by comparing changes in the logical state of gene nodes with transcriptome data. Overall, we observed 71% true predictions, and analyzed sources of errors and discrepancies for the remaining. Though the binary nature of logical (Boolean) models entails inherent limitations, our model constitutes a primary tool for storing regulatory knowledge, searching for incoherencies in hypotheses and evaluating the effect of deleting regulatory elements involved in glucose repression.
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影响因子：
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作者：
Kaniak, A;Xue, ZX;Johnston, M
通讯作者：
Johnston, M
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