Publications about 'chemical reaction networks' |
Articles in journal or book chapters |
In previous work, we have developed an approach to understanding the long-term dynamics of classes of chemical reaction networks, based on rate-dependent Lyapunov functions. In this paper, we show that stronger notions of convergence can be established by proving contraction with respect to non-standard norms. This enables us to show that such networks entrain to periodic inputs. We illustrate our theory with examples from signaling pathways and genetic circuits. |
Metastasis can occur after malignant cells transition from the epithelial phenotype to the mesenchymal phenotype. This transformation allows cells to migrate via the circulatory system and subsequently settle in distant organs after undergoing the reverse transition. The core gene regulatory network controlling these transitions consists of a system made up of coupled SNAIL/miRNA-34 and ZEB1/miRNA-200 subsystems. In this work, we formulate a mathematical model and analyze its long-term behavior. We start by developing a detailed reaction network with 24 state variables. Assuming fast promoter and mRNA kinetics, we then show how to reduce our model to a monotone four-dimensional system. For the reduced system, monotone dynamical systems theory can be used to prove generic convergence to the set of equilibria for all bounded trajectories. The theory does not apply to the full model, which is not monotone, but we briefly discuss results for singularly-perturbed monotone systems that provide a tool to extend convergence results from reduced to full systems, under appropriate time separation assumptions. |
Long-term behaviors of biochemical reaction networks (BRNs) are described by steady states in deterministic models and stationary distributions in stochastic models. Unlike deterministic steady states, stationary distributions capturing inherent fluctuations of reactions are extremely difficult to derive analytically due to the curse of dimensionality. Here, we develop a method to derive analytic stationary distributions from deterministic steady states by transforming BRNs to have a special dynamic property, called complex balancing. Specifically, we merge nodes and edges of BRNs to match in- and out-flows of each node. This allows us to derive the stationary distributions of a large class of BRNs, including autophosphorylation networks of EGFR, PAK1, and Aurora B kinase and a genetic toggle switch. This reveals the unique properties of their stochastic dynamics such as robustness, sensitivity, and multimodality. Importantly, we provide a user-friendly computational package, CASTANET, that automatically derives symbolic expressions of the stationary distributions of BRNs to understand their long-term stochasticity. |
This paper deals with the analysis of the dynamics of chemical reaction networks, developing a theoretical framework based only on graphical knowledge and applying regardless of the particular form of kinetics. This paper introduces a class of networks that are "structurally (mono) attractive", by which we mean that they are incapable of exhibiting multiple steady states, oscillation, or chaos by the virtue of their reaction graphs. These networks are characterized by the existence of a universal energy-like function which we call a Robust Lyapunov function (RLF). To find such functions, a finite set of rank-one linear systems is introduced, which form the extremals of a linear convex cone. The problem is then reduced to that of finding a common Lyapunov function for this set of extremals. Based on this characterization, a computational package, Lyapunov-Enabled Analysis of Reaction Networks (LEARN), is provided that constructs such functions or rules out their existence. An extensive study of biochemical networks demonstrates that LEARN offers a new unified framework. We study basic motifs, three-body binding, and transcriptional networks. We focus on cellular signalling networks including various post-translational modification cascades, phosphotransfer and phosphorelay networks, T-cell kinetic proofreading, ERK signaling, and the Ribosome Flow Model. |
The goal of many single-cell studies on eukaryotic cells is to gain insight into the biochemical reactions that control cell fate and state. This paper introduces the concept of effective stoichiometric space (ESS) to guide the reconstruction of biochemical networks from multiplexed, fixed time-point, single-cell data. In contrast to methods based solely on statistical models of data, the ESS method leverages the power of the geometric theory of toric varieties to begin unraveling the structure of chemical reaction networks (CRN). This application of toric theory enables a data-driven mapping of covariance relationships in single cell measurements into stoichiometric information, one in which each cell subpopulation has its associated ESS interpreted in terms of CRN theory. In the development of ESS we reframe certain aspects of the theory of CRN to better match data analysis. As an application of our approach we process cytomery- and image-based single-cell datasets and identify differences in cells treated with kinase inhibitors. Our approach is directly applicable to data acquired using readily accessible experimental methods such as Fluorescence Activated Cell Sorting (FACS) and multiplex immunofluorescence. |
The study of stochastic biomolecular networks is a key part of systems biology, as such networks play a central role in engineered synthetic biology constructs as well as in naturally occurring cells. This expository paper reviews in a unified way a pair of recent approaches to the finite computation of statistics for chemical reaction networks. |
Biochemical reaction networks in cells frequently consist of reactions with disparate timescales. Stochastic simulations of such multiscale BRNs are prohibitively slow due to the high computational cost incurred in the simulations of fast reactions. One way to resolve this problem is to replace fast species by their stationary conditional expectation values conditioned on slow species. While various approximations schemes for this quasi-steady state approximation have been developed, they often lead to considerable errors. This paper considers two classes of multiscale BRNs which can be reduced by through an exact QSS rather than approximations. Specifically, we assume that fast species constitute either a feedforward network or a complex balanced network. Exact reductions for various examples are derived, and the computational advantages of this approach are illustrated through simulations. |
Chemical systems are inherently stochastic, as reactions depend on random (thermal) motion. This motivates the study of stochastic models, and specifically the Chemical Master Equation (CME), a discrete-space continuous-time Markov process that describes stochastic chemical kinetics. Exact studies using the CME are difficult, and several moment closure tools related to "mass fluctuation kinetics" and "fluctuation-dissipation" formulas can be used to obtain approximations of moments. This paper, in contrast, introduces a class of nonlinear chemical reaction networks for which exact computation is possible, by means of finite-dimensional linear differential equations. This class allows second and higher order reactions, but only under special assumptions on structure and/or conservation laws. |
This paper studies the direction of change of steady states to parameter perturbations in chemical reaction networks, and, in particular, to changes in conserved quantities. Theoretical considerations lead to the formulation of a computational procedure that provides a set of possible signs of such sensitivities. The procedure is purely algebraic and combinatorial, only using information on stoichiometry, and is independent of the values of kinetic constants. Two examples of important intracellular signal transduction models are worked out as an illustration. In these examples, the set of signs found is minimal, but there is no general guarantee that the set found will always be minimal in other examples. The paper also briefly discusses the relationship of the sign problem to the question of uniqueness of steady states in stoichiometry classes. |
New checkable criteria for persistence of chemical reaction networks are proposed, which extend and complement existing ones. The new results allow the consideration of reaction rates which are time-varying, thus incorporating the effects of external signals, and also relax the assumption of existence of global conservation laws, thus allowing for inflows (production) and outflows (degradation). For time-invariant networks parameter-dependent conditions for persistence of certain classes of networks are provided. As an illustration, two networks arising in the systems biology literature are analyzed, namely a hypoxia and an apoptosis network. |
This paper derives new results for certain classes of chemical reaction networks, linking structural to dynamical properties. In particular, it investigates their monotonicity and convergence without making assumptions on the form of the kinetics (e.g., mass-action) of the dynamical equations involved, and relying only on stoichiometric constraints. The key idea is to find an alternative representation under which the resulting system is monotone. As a simple example, the paper shows that a phosphorylation/dephosphorylation process, which is involved in many signaling cascades, has a global stability property. |
Persistency is the property, for differential equations in Rn, that solutions starting in the positive orthant do not approach the boundary. For chemical reactions and population models, this translates into the non-extinction property: provided that every species is present at the start of the reaction, no species will tend to be eliminated in the course of the reaction. This paper provides checkable conditions for persistence of chemical species in reaction networks, using concepts and tools from Petri net theory, and verifies these conditions on various systems which arise in the modeling of cell signaling pathways. |
We analyze certain chemical reaction networks and show that every solution converges to some steady state. The reaction kinetics are assumed to be monotone but otherwise arbitrary. When diffusion effects are taken into account, the conclusions remain unchanged. The main tools used in our analysis come from the theory of monotone dynamical systems. We review some of the features of this theory and provide a self-contained proof of a particular attractivity result which is used in proving our main result. |
This paper provides a necessary and sufficient condition for detectability, and an explicit construction of observers when this condition is satisfied, for chemical reaction networks of the Feinberg-Horn-Jackson zero deficiency type. |
Conference articles |
This is a very summarized version ofthe first part of the paper "Persistence results for chemical reaction networks with time-dependent kinetics and no global conservation laws". |
This paper derives new results for certain classes of chemical reaction networks, linking structural to dynamical properties. In particular, it investigates their monotonicity and convergence without making assumptions on the structure (e.g., mass-action kinetics) of the dynamical equations involved, and relying only on stoichiometric constraints. The key idea is to find a suitable set of coordinates under which the resulting system is cooperative. As a simple example, the paper shows that a phosphorylation/dephosphorylation process, which is involved in many signaling cascades, has a global stability property. |
Monotone systems are dynamical systems for which the flow preserves a partial order. Some applications will be briefly reviewed in this paper. Much of the appeal of the class of monotone systems stems from the fact that roughly, most solutions converge to the set of equilibria. However, this usually requires a stronger monotonicity property which is not always satisfied or easy to check in applications. Following work of J.F. Jiang, we show that monotonicity is enough to conclude global attractivity if there is a unique equilibrium and if the state space satisfies a particular condition. The proof given here is self-contained and does not require the use of any of the results from the theory of monotone systems. We will illustrate it on a class of chemical reaction networks with monotone, but otherwise arbitrary, reaction kinetics. |
Internal reports |
We review in a unified way results for two types of stochastic chemical reaction systems for which moments can be effectively computed: feedforward networks and complex-balanced networks. |
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