Variance reduction for antithetic integral control of stochastic reaction networks

TL;DR

This paper proposes combining antithetic integral feedback with negative feedback in stochastic reaction networks to reduce variance while maintaining robustness, supported by theoretical approximations and numerical validation.

Contribution

It introduces a novel combined control strategy that decreases variance in stochastic networks, extending the antithetic integral control framework with negative feedback.

Findings

Variance can be decreased by increasing negative feedback strength.

The combined control strategy sometimes reduces variance below open-loop levels.

There is a trade-off between variance reduction and settling-time speed.

Abstract

The antithetic integral feedback motif recently introduced in Briat, Gupta & Khammash (Cell Systems, 2017) is known to ensure robust perfect adaptation for the mean dynamics of a given molecular species involved in a complex stochastic biomolecular reaction network. However, it was observed that it also leads to a higher variance in the controlled network than that obtained when using a constitutive (i.e. open-loop) control strategy. This was interpreted as the cost of the adaptation property and may be viewed as a performance deterioration for the overall controlled network. To decrease this variance and improve the performance, we propose to combine the antithetic integral feedback motif with a negative feedback strategy. Both theoretical and numerical results are obtained. The theoretical ones are based on a tailored moment closure method allowing one to obtain approximate expressions for the stationary variance for the controlled network and predict that the variance can indeed be decreased by increasing the strength of the negative feedback. Numerical results verify the accuracy of this approximation and show that the controlled species variance can indeed be decreased, sometimes below its constitutive level. Three molecular networks are considered in order to verify the wide applicability of two types of negative feedback strategies. The main conclusion is that there is a trade-off between the speed of the settling-time of the mean trajectories and the stationary variance of the controlled species; i.e. smaller variance is associated with larger settling-time.