Simulation of E. coli gene regulation including overlapping cell cycles, growth, division, time delays and noise.
Simulation of E. coli gene regulation including overlapping cell cycles, growth, division, time delays and noise.
复制标题
模拟大肠杆菌基因调控，包括重叠细胞周期、生长、分裂、时间延迟和噪声
DOI：
10.1371/journal.pone.0062380
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Luo R;Ye L;Tao C;Wang K
由于生物系统的复杂性，生物网络的模拟是必要的，但有时很复杂。经典的吉莱斯皮随机模拟算法（SSA）及其改进算法被广泛应用于生化反应系统的随机动力学模拟。然而，它仍然是一个挑战，以实现准确和有效的模拟算法的一般反应计划，在不断增长的细胞。在这里，我们提出了一个建模和仿真工具，称为“基因电路”，这是专门开发来模拟基因调控指数增长的细菌细胞（如大肠杆菌）。coli）中的细胞周期重叠。我们的工具整合了这些细胞的三个特定特征，这些特征通常不包括在SSA工具中：1）由于转录和翻译过程导致的蛋白质调节和合成之间的时间延迟; 2）基因剂量的细胞周期依赖性周期变化;以及3）由于体积膨胀和细胞分裂而具有时间依赖性反应速率的化学反应倾向的变化。我们给出了三个生物相关的例子来说明我们的模拟工具在系统生物学和合成生物学的定量研究中的应用。
Due to the complexity of biological systems, simulation of biological networks is necessary but sometimes complicated. The classic stochastic simulation algorithm (SSA) by Gillespie and its modified versions are widely used to simulate the stochastic dynamics of biochemical reaction systems. However, it has remained a challenge to implement accurate and efficient simulation algorithms for general reaction schemes in growing cells. Here, we present a modeling and simulation tool, called ‘GeneCircuits’, which is specifically developed to simulate gene-regulation in exponentially growing bacterial cells (such as E. coli) with overlapping cell cycles. Our tool integrates three specific features of these cells that are not generally included in SSA tools: 1) the time delay between the regulation and synthesis of proteins that is due to transcription and translation processes; 2) cell cycle-dependent periodic changes of gene dosage; and 3) variations in the propensities of chemical reactions that have time-dependent reaction rates as a consequence of volume expansion and cell division. We give three biologically relevant examples to illustrate the use of our simulation tool in quantitative studies of systems biology and synthetic biology.