Uniform design-based sensitivity analysis of circadian rhythm model in Neurospora

Abstract

The period of circadian rhythms often fluctuates around 24 h due to the changes of environmental factors. Actually, the period varies directly with the ambient stimuli which could be expressed as different values of the kinetic parameters included in the circadian models. Therefore, to study the relationships between kinetic parameters and period, which is also known as sensitivity analysis, is a more convenient and direct way than experimental observation. The reduced circadian rhythm model for Neurospora, including nine kinetic parameters and three species, is selected to study the above-mentioned relationships. In order to provide an efficient and accurate sensitivity analysis method, the uniform design is adopted for the sampling strategy in which the values of these kinetic parameters could vary within a relative large region. Regression analysis is then implemented according to the recorded periods of frq mRNA with respect to different parameter sets. We obtain a quadratic model which could quantitatively explain the influences of kinetic parameters and external factors on the period and educe the conclusions accordant with other studies. Compared with another sensitivity analysis method, the Morris method, the sequence of the importance of parameters is consistent. Besides, the regression model could provide the prediction of period for a given ambient stimuli or different values of parameters. Uniform design-based sensitivity analysis can be successfully applied in the complicated circadian models.