Sensitivity analysis of circadian entrainment in the space of phase response curves

TL;DR

This paper introduces a sensitivity analysis method for oscillator models based on phase response curves, enabling efficient exploration of high-dimensional parameter spaces relevant to circadian rhythms.

Contribution

The paper develops a novel sensitivity analysis tool specifically designed for phase response curves, overcoming the curse of dimensionality in high-dimensional oscillator models.

Findings

The method effectively analyzes circadian rhythm models.

It reveals key parameters influencing oscillator behavior.

The tool is applicable to complex biological models.

Abstract

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input--output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical exploration of the parameter space. Application of this tool to a state-of-the-art model of circadian rhythms suggests that it can be useful and instrumental to biological investigations.