Phys Biol. 2021 Mar 15;18(3):036002
We consider a generic biological process described by a dynamical system, subject to an input signal with a high-frequency periodic component. The rapid oscillations of the input signal induce inherently multiscale dynamics, motivating order-reduction techniques. It is intuitive that the system behaviour is well approximated by its response to the averaged input signal. However, changes to the high-frequency component that preserve the average signal are beyond the reach of such intuitive reasoning. In this study, we explore system response under the influence of such an input signal by exploiting the timescale separation between high-frequency input variations and system response time. Employing the asymptotic method of multiple scales, we establish that, in some circumstances, the intuitive approach is simply the leading-order asymptotic contribution. We focus on higher-order corrections that capture the response to the details of the high-frequency component beyond its average. This approach achieves a reduction in system complexity while providing valuable insight into the structure of the response to the oscillations. We develop the general theory for nonlinear systems, while highlighting the important case of systems affine in the state and the input signal, presenting examples of both discrete and continuum state spaces. Importantly, this class of systems encompasses biochemical reaction networks described by the chemical master equation and its continuum approximations. Finally, we apply the framework to a nonlinear system describing mRNA translation and protein expression previously studied in the literature. The analysis shines new light on several aspects of the system quantification and both extends and simplifies results previously obtained.