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German Enciso

Publications and source records attributed to German Enciso.

7 recordsLinked to original sources

Identifiability of Stochastically Modelled Reaction Networks

Chemical reaction networks describe interactions between biochemical species. Once an underlying reaction network is given for a biochemical system, the system dynamics can be modelled with various mathematical frameworks such as continuous time Markov processes. In this manuscript, the identifiability of the underlying network structure with a given stochastic system dynamics is studied. It is shown that some data types related to the associated stochastic dynamics can uniquely identify the underlying network structure as well as the system parameters. The accuracy of the presented network inference is investigated when given dynamical data is obtained via stochastic simulations.

math.PR

Slack Reactants: A State-Space Truncation Framework to Estimate Quantitative Behavior of the Chemical Master Equation

State space truncation methods are widely used to approximate solutions of the chemical master equation. While most methods of this kind focus on truncating the state space directly, in this work we propose modifying the underlying chemical reaction network by introducing \emph{slack reactants} that indirectly truncate the state space. More specifically, slack reactants introduce an expanded chemical reaction network and impose a truncation scheme based on user defined properties, such as mass-conservation. This network structure allows us to prove inheritance of special properties of the original model, such as irreducibility and complex balancing. We use the network structure imposed by slack reactants to prove the convergence of the stationary distribution and first arrival times. We then provide examples comparing our method with the stationary finite state projection and finite buffer methods. Our slack reactant system appears to be more robust than some competing methods with respect to calculating first arrival times.

math.PR

Absolutely Robust Controllers for Chemical Reaction Networks

In this work, we design a type of controller that consists of adding a specific set of reactions to an existing mass-action chemical reaction network in order to control a target species. This set of reactions is effective for both deterministic and stochastic networks, in the latter case controlling the mean as well as the variance of the target species. We employ a type of network property called absolute concentration robustness (ACR). We provide applications to the control of a multisite phosphorylation model as well as a receptor-ligand signaling system. For this framework, we use the so-called deficiency zero theorem from chemical reaction network theory as well as multiscaling model reduction methods. We show that the target species has approximately Poisson distribution with the desired mean. We further show that ACR controllers can bring robust perfect adaptation to a target species and are complementary to a recently introduced antithetic feedback controller used for stochastic chemical reactions.

q-bio.MN

Accuracy of Multiscale Reduction for Stochastic Reaction Systems

Stochastic models of chemical reaction networks are an important tool to describe and analyze noise effects in cell biology. When chemical species and reaction rates in a reaction system have different orders of magnitude, the associated stochastic system is often modeled in a multiscale regime. It is known that multiscale models can be approximated with a reduced system such as mean field dynamics or hybrid systems, but the accuracy of the approximation remains unknown. In this paper, we estimate the probability distribution of low copy species in multiscale stochastic reaction systems under short-time scale. We also establish an error bound for this approximation. Throughout the manuscript, typical mass action systems are mainly handled, but we also show that the main theorem can extended to general kinetics, which generalizes existing results in the literature. Our approach is based on a direct analysis of the Kolmogorov equation, in contrast to classical approaches in the existing literature.

math.PR

Stochastic analysis of biochemical reaction networks with absolute concentration robustness

It has recently been shown that structural conditions on the reaction network, rather than a 'fine-tuning' of system parameters, often suffice to impart 'absolute concentration robustness' on a wide class of biologically relevant, deterministically modeled mass-action systems [Shinar and Feinberg, Science, 2010]. We show here that fundamentally different conclusions about the long-term behavior of such systems are reached if the systems are instead modeled with stochastic dynamics and a discrete state space. Specifically, we characterize a large class of models that exhibit convergence to a positive robust equilibrium in the deterministic setting, whereas trajectories of the corresponding stochastic models are necessarily absorbed by a set of states that reside on the boundary of the state space, i.e. the system undergoes an extinction event. If the time to extinction is large relative to the relevant time-scales of the system, the process will appear to settle down to a stationary distribution long before the inevitable extinction will occur. This quasi-stationary distribution is considered for two systems taken from the literature, and results consistent with absolute concentration robustness are recovered by showing that the quasi-stationary distribution of the robust species approaches a Poisson distribution.

math.PR

Extremely chaotic Boolean networks

It is an increasingly important problem to study conditions on the structure of a network that guarantee a given behavior for its underlying dynamical system. In this paper we report that a Boolean network may fall within the chaotic regime, even under the simultaneous assumption of several conditions which in randomized studies have been separately shown to correlate with ordered behavior. These properties include using at most two inputs for every variable, using biased and canalyzing regulatory functions, and restricting the number of negative feedback loops. We also prove for n-dimensional Boolean networks that if in addition the number of outputs for each variable is bounded and there exist periodic orbits of length c^n for c sufficiently close to 2, any network with these properties must have a large proportion of variables that simply copy previous values of other variables. Such systems share a structural similarity to a relatively small Turing machine acting on one or several tapes.

q-bio.MN

Large attractors in cooperative bi-quadratic Boolean networks. Part II

Boolean networks have been the object of much attention, especially since S. Kauffman proposed them in the 1960's as models for gene regulatory networks. These systems are characterized by being defined on a Boolean state space and by simultaneous updating at discrete time steps. Of particular importance for biological applications are networks in which the indegree for each variable is bounded by a fixed constant, as was stressed by Kauffman in his original papers. An important question is which conditions on the network topology can rule out exponentially long periodic orbits in the system. In this paper we consider cooperative systems, i.e. systems with positive feedback interconnections among all variables, which in a continuous setting guarantees a very stable dynamics. In Part I of this paper we presented a construction that shows that for an arbitrary constant 0<c<2 and sufficiently large n there exist n-dimensional Boolean cooperative networks in which both the indegree and outdegree of each for each variable is bounded by two (bi-quadratic networks) and which nevertheless contain periodic orbits of length at least c^n. In this part, we prove an inverse result showing that for sufficiently large n and for 0<c<2 sufficiently close to 2, any n-dimensional cooperative, bi-quadratic Boolean network with a cycle of length at least c^n must have a large proportion of variables with indegree 1. Such systems therefore share a structural similarity to the systems constructed in Part I.

q-bio.MN