Quantitative performance metrics for robustness in circadian rhythms
Quantitative performance metrics for robustness in circadian rhythms
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DOI：
10.1093/bioinformatics/btl627
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发表时间：
2007-02-01
期刊：
影响因子：
5.8
通讯作者：
Doyle, Francis J., III
中科院分区：
文献类型：
--
作者：
Bagheri, Neda;Stelling, Joerg;Doyle, Francis J., III
动机：敏感性分析提供了关键的措施，有助于解开负责生物网络的鲁棒性能的设计原则。这些指标使研究人员能够全面调查模型性能，开发更逼真的模型，并设计信息丰富的实验。然而，振荡系统的灵敏度分析侧重于周期和幅度特性，而生物相关的影响phase是ignored.Results：在这里，我们引入了一套新的基于相位的性能灵敏度指标：周期，相位，校正相位和相对相位。这两个国家和阶段为基础的工具适用于自由运行的果蝇和小家鼠昼夜节律模型。每个指标产生唯一的敏感度值，用于将参数从最不敏感到最敏感进行排序。由此产生的秩分布之间的相似性强烈建议相对于参数函数和类型的敏感性的保守。例如，一个一致的结果是，生物振荡器的模型性能对全局参数比局部（即昼夜节律特异性）参数更敏感。这些分布之间的差异突出了各个指标对性能的定义，因为特定的参数敏感度值取决于定义的指标或输出。
Motivation: Sensitivity analysis provides key measures that aid in unraveling the design principles responsible for the robust performance of biological networks. Such metrics allow researchers to investigate comprehensively model performance, to develop more realistic models, and to design informative experiments. However, sensitivity analysis of oscillatory systems focuses on period and amplitude characteristics, while biologically relevant effects on phase are neglected.Results: Here, we introduce a novel set of phase-based sensitivity metrics for performance: period, phase, corrected phase and relative phase. Both state- and phase-based tools are applied to free-running Drosophila melanogaster and Mus musculus circadian models. Each metric produces unique sensitivity values used to rank parameters from least to most sensitive. Similarities among the resulting rank distributions strongly suggest a conservation of sensitivity with respect to parameter function and type. A consistent result, for instance, is that model performance of biological oscillators is more sensitive to global parameters than local (i.e. circadian specific) parameters. Discrepancies among these distributions highlight the individual metrics' definition of performance as specific parametric sensitivity values depend on the defined metric, or output.