Identifying parameter regions for multistationarity

Mathematical modelling has become an established tool for studying the dynamics of biological systems. Current applications range from building models that reproduce quantitative data to identifying systems with predefined qualitative features, such as switching behaviour, bistability or oscillations. Mathematically, the latter question amounts to identifying parameter values associated with a given qualitative feature. We introduce a procedure to partition the parameter space of a parameterized system of ordinary differential equations into regions for which the system has a unique or multiple equilibria. The procedure is based on the computation of the Brouwer degree, and it creates a multivariate polynomial with parameter depending coefficients. The signs of the coefficients determine parameter regions with and without multistationarity. A particular strength of the procedure is the avoidance of numerical analysis and parameter sampling. The procedure consists of a number of steps. Each of these steps might be addressed algorithmically using various computer programs and available software, or manually. We demonstrate our procedure on several models of gene transcription and cell signalling, and show that in many cases we obtain a complete partitioning of the parameter space with respect to multistationarity.Comment: In this version the paper has been substantially rewritten and reorganised. Theorem 1 has been reformulated and Corollary 1 adde

A unified view on bipartite species-reaction and interaction graphs for chemical reaction networks

The Jacobian matrix of a dynamic system and its principal minors play a prominent role in the study of qualitative dynamics and bifurcation analysis. When interpreting the Jacobian as an adjacency matrix of an interaction graph, its principal minors correspond to sets of disjoint cycles in this graph and conditions for various dynamic behaviors can be inferred from its cycle structure. For chemical reaction systems, more fine-grained analyses are possible by studying a bipartite species-reaction graph. Several results on injectivity, multistationarity, and bifurcations of a chemical reaction system have been derived by using various definitions of such bipartite graph. Here, we present a new definition of the species-reaction graph that more directly connects the cycle structure with determinant expansion terms, principal minors, and the coefficients of the characteristic polynomial and encompasses previous graph constructions as special cases. This graph has a direct relation to the interaction graph, and properties of cycles and sub-graphs can be translated in both directions. A simple equivalence relation enables to decompose determinant expansions more directly and allows simpler and more direct proofs of previous results.Comment: 27 pages. submitted to J. Math. Bio

A passivity-based stability criterion for a class of interconnected systems and applications to biochemical reaction networks

This paper presents a stability test for a class of interconnected nonlinear systems motivated by biochemical reaction networks. One of the main results determines global asymptotic stability of the network from the diagonal stability of a "dissipativity matrix" which incorporates information about the passivity properties of the subsystems, the interconnection structure of the network, and the signs of the interconnection terms. This stability test encompasses the "secant criterion" for cyclic networks presented in our previous paper, and extends it to a general interconnection structure represented by a graph. A second main result allows one to accommodate state products. This extension makes the new stability criterion applicable to a broader class of models, even in the case of cyclic systems. The new stability test is illustrated on a mitogen activated protein kinase (MAPK) cascade model, and on a branched interconnection structure motivated by metabolic networks. Finally, another result addresses the robustness of stability in the presence of diffusion terms in a compartmental system made out of identical systems.Comment: See http://www.math.rutgers.edu/~sontag/PUBDIR/index.html for related (p)reprint

A delay-dependent LMI approach to dynamics analysis of discrete-time recurrent neural networks with time-varying delays

This is the post print version of the article. The official published version can be obtained from the link below - Copyright 2007 Elsevier Ltd.In this Letter, the analysis problem for the existence and stability of periodic solutions is investigated for a class of general discrete-time recurrent neural networks with time-varying delays. For the neural networks under study, a generalized activation function is considered, and the traditional assumptions on the boundedness, monotony and differentiability of the activation functions are removed. By employing the latest free-weighting matrix method, an appropriate Lyapunov–Krasovskii functional is constructed and several sufficient conditions are established to ensure the existence, uniqueness, and globally exponential stability of the periodic solution for the addressed neural network. The conditions are dependent on both the lower bound and upper bound of the time-varying time delays. Furthermore, the conditions are expressed in terms of the linear matrix inequalities (LMIs), which can be checked numerically using the effective LMI toolbox in MATLAB. Two simulation examples are given to show the effectiveness and less conservatism of the proposed criteria.This work was supported in part by the National Natural Science Foundation of China under Grant 50608072, an International Joint Project sponsored by the Royal Society of the UK and the National Natural Science Foundation of China, and the Alexander von Humboldt Foundation of Germany