CADLIVE dynamic simulator: Direct link of biochemical networks to dynamic models
CADLIVE dynamic simulator: Direct link of biochemical networks to dynamic models
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DOI：
10.1101/gr.3463705
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发表时间：
2005-04-01
期刊：
影响因子：
7
通讯作者：
Iwasaki, R
中科院分区：
文献类型：
--
作者：
Kurata, H;Masaki, K;Iwasaki, R
我们开发了CADLIVE（生命系统计算机辅助设计）模拟器，该模拟器提供了一种基于规则的自动方式，将生化网络图转换为动态模型，从而可以模拟其动力学，而无需将所有反应精确到动力学参数的细节。模拟器支持由以前开发的GUI编辑器生成的生化反应图。注意，之前已经发布了GUI编辑器的部分，但是还没有发布模拟器。为了将生化网络映射直接链接到动态模拟，我们创建了三层两阶段的策略，并在XML表示中使用有效的转换规则。该策略将分子网络划分为基因层、蛋白质层和代谢层三层，并将转化过程划分为两个阶段。一旦提供了生化图谱，CADLIVE就会自动建立一个数学模型，从而便于模拟和分析它。为了证明CADLIVE的可行性，我们分析了大肠杆菌氮同化系统（64个方程，64个变量），该系统由多个复杂的负反馈回路和正反馈回路组成。CADLIVE预测glnK基因负责氮相关（nitrogen- relevant, Ntr）基因表达相对于氨浓度的滞后性或可逆性，支持了Ntr基因失控表达的实验观察。
We have developed the CADLIVE (Computer-Aided Design of LIVing systEms) Simulator that provided a rule-based automatic way to convert biochemical network maps into dynamic models, which enables simulating their dynamics without going through all of the reactions down to the details of exact kinetic parameters. The simulator supports the biochemical reaction maps that are generated by the previously developed GUI editor. Notice that the part of the GUI editor had been previously published, but, as yet, not the simulator. To directly link biochemical network maps to dynamic simulation, we have created the strategy of three layers and two stages with the efficient conversion rules in an XML representation. This strategy divides a molecular network into three layers, i.e., gene, protein, and metabolic layers, and partitions the conversion process into two stages. Once a biochemical map is provided, CADLIVE automatically builds a mathematical model, thereby facilitating one to simulate and analyze it. In order to demonstrate the feasibility of CADLIVE, we analyzed the Escherichia coli nitrogen-assimilation system (64 equations with 64 variables) that consists of multiple and complicated negative and positive feedback loops. CADLIVE predicted that the glnK gene is responsible for hysteresis or reversibility of nitrogen-related (Ntr) gene expression with respect to the ammonia concentration, supporting the experimental observation of the runaway expression of the Ntr genes.