P-matrices and signed digraphs

We associate a signed digraph with a list of matrices whose dimensions permit them to be multiplied, and whose product is square. Cycles in this graph have a parity, that is, they are either even (termed e-cycles) or odd (termed o-cycles). The absence of e-cycles in the graph is shown to imply that the matrix product is a P0-matrix, i.e., all of its principal minors are nonnegative. Conversely, the presence of an e-cycle is shown to imply that there exists a list of matrices associated with the graph whose product fails to be a P0-matrix. The results generalise a number of previous results relating P- and P0-matrices to graphs

Monotonicity in chemical reaction systems

This paper discusses the question of when the dynamical systems arising from chemical reaction networks are monotone, preserving an order induced by some proper cone. The reaction systems studied are defined by the reaction network structure while the kinetics is only constrained very weakly. Necessary and sufficient conditions on cones preserved by these systems are presented. Linear coordinate changes which make a given reaction system cooperative are characterised. Also discussed is when a reaction system restricted to an invariant subspace is cone preserving, even when the system fails to be cone preserving on the whole of phase space. Many of the proofs allow explicit construction of preserved cones. Numerous examples of chemical reaction systems are presented to illustrate the results

Inheritance of oscillation in chemical reaction networks

Some results are presented on how oscillation is inherited by chemical reaction networks (CRNs) when they are built in natural ways from smaller oscillatory networks. The main results describe four important ways in which a CRN can be enlarged while preserving its capacity for oscillation. The results are for general CRNs, not necessarily fully open, but lead to an important corollary for fully open networks: if a fully open CRN R with mass action kinetics admits a nondegenerate (resp., linearly stable) periodic orbit, then so do all such CRNs which include R as an induced subnetwork. This claim holds for other classes of kinetics, but fails, in general, for CRNs which are not fully open. Where analogous results for multistationarity can be proved using the implicit function theorem alone, the results here call on regular and singular perturbation theory. Equipped with these results and with the help of some analysis and numerical simulation, lower bounds are put on the proportion of small fully open CRNs capable of stable oscillation under various assumptions on the kinetics. This exploration suggests that small oscillatory motifs are an important source of oscillation in CRNs

Splitting reactions preserves nondegenerate behaviors in chemical reaction networks

A family of results, referred to as inheritance results, tell us which enlargements of a chemical reaction network (CRN) preserve its capacity for nontrivial behaviours such as multistationarity and oscillation. In this paper, the following inheritance result is proved: under mild assumptions, splitting chemical reactions and inserting complexes involving some new chemical species preserves the capacity of a mass action CRN for multiple nondegenerate equilibria and/or periodic orbits. The claim has been proved previously for equilibria alone; however, the generalisation to include oscillation involves extensive development of rather different techniques. Several inheritance results for multistationarity and oscillation in mass action CRNs, including the main result of this paper, are gathered into a single theorem. Examples are presented showing how these results can be used together to make claims about reaction networks based on knowledge of their subnetworks. The examples include some networks of biological importance

Graph-theoretic conditions for injectivity of functions on rectangular domains

This paper presents sufficient graph-theoretic conditions for injectivity of collections of differentiable functions on rectangular subsets of R^n . The results have implications for the possibility of multiple fixed points of maps and flows. Well-known results on systems with signed Jacobians are shown to be easy corollaries of more general results presented here

Some results on injectivity and multistationarity in chemical reaction networks

The goal of this paper is to gather and develop some necessary and sufficient criteria for injectivity and multistationarity in vector fields associated with a chemical reaction network under a variety of more or less general assumptions on the nature of the network and the reaction rates. The results are primarily linear algebraic or matrix-theoretic, with some graph-theoretic results also mentioned. Several results appear in, or are close to, results in the literature. Here, we emphasise the connections between the results, and where possible, present elementary proofs which rely solely on basic linear algebra and calculus. A number of examples are provided to illustrate the variety of subtly different conclusions which can be reached via different computations. In addition, many of the computations are implemented in a web-based open source platform, allowing the reader to test examples including and beyond those analysed in the paper

The smallest bimolecular mass action reaction networks admitting Andronov–Hopf bifurcation

We address the question of which small, bimolecular, mass action chemical reaction networks (CRNs) are capable of Andronov–Hopf bifurcation (from here on abbreviated to ‘Hopf bifurcation’). It is easily shown that any such network must have at least three species and at least four irreversible reactions, and one example of such a network with exactly three species and four reactions was previously known due to Wilhelm. In this paper, we develop both theory and computational tools to fully classify three-species, four-reaction, bimolecular CRNs, according to whether they admit or forbid Hopf bifurcation. We show that there are, up to a natural equivalence, 86 minimal networks which admit nondegenerate Hopf bifurcation. Amongst these, we are able to decide which admit supercritical and subcritical bifurcations. Indeed, there are 25 networks which admit both supercritical and subcritical bifurcations, and we can confirm that all 25 admit a nondegenerate Bautin bifurcation. A total of 31 networks can admit more than one nondegenerate periodic orbit. Moreover, 29 of these networks admit the coexistence of a stable equilibrium with a stable periodic orbit. Thus, fairly complex behaviours are not very rare in these small, bimolecular networks. Finally, we can use previously developed theory on the inheritance of dynamical behaviours in CRNs to predict the occurrence of Hopf bifurcation in larger networks which include the networks we find here as subnetworks in a natural sense

Graph-theoretic criteria for injectivity and unique equilibria in general chemical reaction systems

In this paper we discuss the question of how to decide when a general chemical reaction system is incapable of admitting multiple equilibria, regardless of parameter values such as reaction rate constants, and regardless of the type of chemical kinetics, such as mass-action kinetics, Michaelis-Menten kinetics, etc. Our results relate previously described linear algebraic and graph-theoretic conditions for injectivity of chemical reaction systems. After developing a translation between the two formalisms, we show that a graph-theoretic test developed earlier in the context of systems with mass action kinetics, can be applied to reaction systems with arbitrary kinetics. The test, which is easy to implement algorithmically, and can often be decided without the need for any computation, rules out the possibility of multiple equilibria for the systems in question

The inheritance of nondegenerate multistationarity in chemical reaction networks

We study how the properties of allowing multiple positive nondegenerate equilibria (MPNE) and multiple positive linearly stable equilibria (MPSE) are inherited in chemical reaction networks (CRNs). Specifically, when is it that we can deduce that a CRN admits MPNE or MPSE based on analysis of its subnetworks? Using basic techniques from analysis we are able to identify a number of situations where MPNE and MPSE are inherited as we build up a network. Some of these modifications are known while others are new, but all results are proved using the same basic framework, which we believe will yield further results. The results are presented primarily for mass action kinetics, although with natural, and in some cases immediate, generalisation to other classes of kinetics

Local and global stability of equilibria for a class of chemical reaction networks

A class of chemical reaction networks is described with the property that each positive equilibrium is locally asymptotically stable relative to its stoichiometry class, an invariant subspace on which it lies. The reaction systems treated are characterized primarily by the existence of a certain factorization of their stoichiometric matrix and strong connectedness of an associated graph. Only very mild assumptions are made about the rates of reactions, and, in particular, mass action kinetics are not assumed. In many cases, local asymptotic stability can be extended to global asymptotic stability of each positive equilibrium relative to its stoichiometry class. The results are proved via the construction of Lyapunov functions whose existence follows from the fact that the reaction networks define monotone dynamical systems with increasing integrals