Discrepancies between extinction events and boundary equilibria in reaction networks

TL;DR

This paper investigates the relationship between deterministic and stochastic reaction network models, disproving some long-held conjectures about their correspondence, especially in cases with absolute concentration robustness.

Contribution

The paper provides counterexamples showing that long-term behaviors of deterministic and stochastic models do not always align, challenging previous conjectures in reaction network theory.

Findings

Disproved the conjecture that positive recurrence implies positive equilibria.

Disproved the link between boundary equilibria and extinction events.

Counterexamples exist even in mass-conserving, bimolecular networks with robustness.

Abstract

Reaction networks are mathematical models of interacting chemical species that are primarily used in biochemistry. There are two modeling regimes that are typically used, one of which is deterministic and one that is stochastic. In particular, the deterministic model consists of an autonomous system of differential equations, whereas the stochastic system is a continuous time Markov chain. Connections between the two modeling regimes have been studied since the seminal paper by Kurtz (1972), where the deterministic model is shown to be a limit of a properly rescaled stochastic model over compact time intervals. Further, more recent studies have connected the long-term behaviors of the two models when the reaction network satisfies certain graphical properties, such as weak reversibility and a deficiency of zero. These connections have led some to conjecture a link between the long-term behavior of the two models exists, in some sense. In particular, one is tempted to believe that positive recurrence of all states for the stochastic model implies the existence of positive equilibria in the deterministic setting, and that boundary equilibria of the deterministic model imply the occurrence of an extinction event in the stochastic setting. We prove in this paper that these implications do not hold in general, even if restricting the analysis to networks that are bimolecular and that conserve the total mass. In particular, we disprove the implications in the special case of models that have absolute concentration robustness, thus answering in the negative a conjecture stated in the literature in 2014.