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Improvement of the memory function of a mutual repression network in a stochastic environment by negative autoregulation.
BMC Bioinformatics ( IF 2.9 ) Pub Date : 2019-12-27 , DOI: 10.1186/s12859-019-3315-2
A B M Shamim Ul Hasan 1, 2 , Hiroyuki Kurata 2 , Sebastian Pechmann 1
Affiliation  

BACKGROUND Cellular memory is a ubiquitous function of biological systems. By generating a sustained response to a transient inductive stimulus, often due to bistability, memory is central to the robust control of many important biological processes. However, our understanding of the origins of cellular memory remains incomplete. Stochastic fluctuations that are inherent to most biological systems have been shown to hamper memory function. Yet, how stochasticity changes the behavior of genetic circuits is generally not clear from a deterministic analysis of the network alone. Here, we apply deterministic rate equations, stochastic simulations, and theoretical analyses of Fokker-Planck equations to investigate how intrinsic noise affects the memory function in a mutual repression network. RESULTS We find that the addition of negative autoregulation improves the persistence of memory in a small gene regulatory network by reducing stochastic fluctuations. Our theoretical analyses reveal that this improved memory function stems from an increased stability of the steady states of the system. Moreover, we show how the tuning of critical network parameters can further enhance memory. CONCLUSIONS Our work illuminates the power of stochastic and theoretical approaches to understanding biological circuits, and the importance of considering stochasticity when designing synthetic circuits with memory function.

中文翻译:

通过负自动调节改善随机环境中互阻网络的存储功能。

背景技术细胞记忆是生物系统的普遍功能。通过产生对瞬态感应刺激的持续响应(通常是由于双稳态),记忆对于许多重要生物过程的稳健控制至关重要。但是,我们对细胞记忆起源的理解仍然不完整。大多数生物系统固有的随机波动已显示出会阻碍记忆功能。然而,仅从对网络的确定性分析中,通常尚不清楚随机性如何改变遗传电路的行为。在这里,我们应用确定性速率方程,随机模拟和Fokker-Planck方程的理论分析,以研究固有噪声如何影响互压网络中的记忆功能。结果我们发现,通过减少随机波动,添加负自动调节可改善小型基因调节网络中记忆的持久性。我们的理论分析表明,这种改进的记忆功能源于系统稳态的增加的稳定性。此外,我们展示了关键网络参数的调整如何进一步增强内存。结论我们的工作阐明了理解生物学电路的随机和理论方法的力量,以及在设计具有记忆功能的合成电路时考虑随机性的重要性。我们的理论分析表明,这种改进的记忆功能源于系统稳态的增加的稳定性。此外,我们展示了关键网络参数的调整如何进一步增强内存。结论我们的工作阐明了理解生物学电路的随机和理论方法的力量,以及在设计具有记忆功能的合成电路时考虑随机性的重要性。我们的理论分析表明,这种改进的记忆功能源于系统稳态的增加的稳定性。此外,我们展示了关键网络参数的调整如何进一步增强内存。结论我们的工作阐明了理解生物学电路的随机和理论方法的力量,以及在设计具有记忆功能的合成电路时考虑随机性的重要性。
更新日期:2019-12-30
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