Department of Biological Sciences, Institute of Molecular Plant Sciences, University of Edinburgh, Edinburgh, United Kingdom.
PLoS One. 2010 Nov 30;5(11):e13867. doi: 10.1371/journal.pone.0013867.
Sensitivity and robustness are essential properties of circadian clock systems, enabling them to respond to the environment but resist noisy variations. These properties should be recapitulated in computational models of the circadian clock. Highly nonlinear kinetics and multiple loops are often incorporated into models to match experimental time-series data, but these also impact on model properties for clock models.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we study the consequences of complicated structure and nonlinearity using simple Goodwin-type oscillators and the complex Arabidopsis circadian clock models. Sensitivity analysis of the simple oscillators implies that an interlocked multi-loop structure reinforces sensitivity/robustness properties, enhancing the response to external and internal variations. Furthermore, we found that reducing the degree of nonlinearity could sometimes enhance the robustness of models, implying that ad hoc incorporation of nonlinearity could be detrimental to a model's perceived credibility.
The correct multi-loop structure and degree of nonlinearity are therefore critical in contributing to the desired properties of a model as well as its capacity to match experimental data.
敏感性和鲁棒性是生物钟系统的基本属性，使它们能够对外界环境做出响应，同时抵抗嘈杂的变化。这些特性应该在生物钟的计算模型中得到再现。高度非线性动力学和多个环路通常被纳入模型中以匹配实验时间序列数据，但这些也会影响时钟模型的模型特性。
方法/主要发现：在这里，我们使用简单的 Goodwin 型振荡器和复杂的拟南芥生物钟模型研究了复杂结构和非线性的后果。简单振荡器的敏感性分析表明，互锁的多环路结构增强了敏感性/鲁棒性特性，增强了对外部和内部变化的响应。此外，我们发现降低非线性度有时可以增强模型的鲁棒性，这意味着专门引入非线性可能会损害模型的可信度。
因此，正确的多环路结构和非线性程度对于模型的预期特性以及其匹配实验数据的能力都是至关重要的。
