Exploring multiplicity conditions in enzymatic reaction networks

Otero-Muras, Irene; Banga, Julio R.; Alonso, Antonio A.

doi:10.1002/btpr.112

Cited by 15 publications

(27 citation statements)

References 10 publications

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“…As proved in [29], the elements of a basis for can be obtained from the left kernel of the matrix:where Y is the molecularity matrix and is the matrix with columns being the vectors defined in (5).…”

Section: Discussionmentioning

confidence: 99%

“…In a previous paper [29] we have introduced the parameters into the picture, providing a canonical expression for the equilibrium manifold in terms of the kinetic parameters and the so called deficiency parameters of the network. The concept of network layout , introduced in [29] as the difference between the deficiency of a network () and the dimension of the equilibrium manifold (), allowed us to classify biochemical reaction networks in three groups: proper networks (), overdimensioned networks () and underdimensioned networks ().…”

Section: Introductionmentioning

confidence: 99%

“…In this work, we formalize the geometric intuition in [29] to derive a sufficient condition for multistationarity which is general, i.e. applies to networks where the dimension of the equilibrium manifold is lower, equal or greater than the deficiency.…”

Section: Introductionmentioning

confidence: 99%

“…In a previous paper [29], we have exploited the graph structure of biochemical networks to obtain an expression of the locus of equilibria –the set of points such that in (7)– in terms of as many parameters as the deficiency of the network. For a class of networks (the so called proper networks ) we were able to partition (by continuation of variation parameters associated with the deficiency) the space of kinetic parameters in regions with different qualitative dynamic behavior.…”

Section: Introductionmentioning

confidence: 99%

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Characterizing Multistationarity Regimes in Biochemical Reaction Networks

2012

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Switch like responses appear as common strategies in the regulation of cellular systems. Here we present a method to characterize bistable regimes in biochemical reaction networks that can be of use to both direct and reverse engineering of biological switches. In the design of a synthetic biological switch, it is important to study the capability for bistability of the underlying biochemical network structure. Chemical Reaction Network Theory (CRNT) may help at this level to decide whether a given network has the capacity for multiple positive equilibria, based on their structural properties. However, in order to build a working switch, we also need to ensure that the bistability property is robust, by studying the conditions leading to the existence of two different steady states. In the reverse engineering of biological switches, knowledge collected about the bistable regimes of the underlying potential model structures can contribute at the model identification stage to a drastic reduction of the feasible region in the parameter space of search. In this work, we make use and extend previous results of the CRNT, aiming not only to discriminate whether a biochemical reaction network can exhibit multiple steady states, but also to determine the regions within the whole space of parameters capable of producing multistationarity. To that purpose we present and justify a condition on the parameters of biochemical networks for the appearance of multistationarity, and propose an efficient and reliable computational method to check its satisfaction through the parameter space.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Characterizing Multistationarity Regimes in Biochemical Reaction Networks

2012

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“…According to the deficiency and the dimension of the equilibrium manifold, we classify the networks into three groups [51]:…”

Section: Methodsmentioning

confidence: 99%

Chemical Reaction Network Theory elucidates sources of multistability in interferon signaling

2017

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Bistability has important implications in signaling pathways, since it indicates a potential cell decision between alternative outcomes. We present two approaches developed in the framework of the Chemical Reaction Network Theory for easy and efficient search of multiple steady state behavior in signaling networks (both with and without mass conservation), and apply them to search for sources of bistability at different levels of the interferon signaling pathway. Different type I interferon subtypes and/or doses are known to elicit differential bioactivities (ranging from antiviral, antiproliferative to immunomodulatory activities). How different signaling outcomes can be generated through the same receptor and activating the same JAK/STAT pathway is still an open question. Here, we detect bistability at the level of early STAT signaling, showing how two different cell outcomes are achieved under or above a threshold in ligand dose or ligand-receptor affinity. This finding could contribute to explain the differential signaling (antiviral vs apoptotic) depending on interferon dose and subtype (α vs β) observed in type I interferons.

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