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A Computational Approach to Multistationarity in Poly-PL Kinetic Systems

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 Added by Bryan Hernandez
 Publication date 2020
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and research's language is English




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One important question that interests those who work in chemical reaction network theory (CRNT) is this: Does the system obtained from a reaction network admit a positive equilibrium and if it does, can there be more than one within a stoichiometric class? The higher deficiency algorithm (HDA) of Ji and Feinberg provided a method of determining the multistationarity capacity of a CRN with mass action kinetics (MAK). An extension of this, called Multistationarity Algorithm (MSA), recently came into the scene tackling CRNs with power law kinetics (PLK), a kinetic system which is more general (having MAK systems as a special case). For this paper, we provide a computational approach to study the multistationarity feature of reaction networks endowed with kinetics which are non-negative linear combinations of power law functions called poly-PL kinetics (PYK). The idea is to use MSA and combine it with a transformation called STAR-MSC (i.e., $S$-invariant Termwise Addition of Reactions via Maximal Stoichiometric Coefficients) producing PLKs that are dynamically equivalent to PYKs. This leads us to being able to determinine the multistationarity capacity of a much larger class of kinetic systems. We show that if the transformed dynamically equivalent PLK system is multistationary for a stoichiometric class for a set of particular rate constants, then so is its original corresponding PYK system. Moreover, the monostationarity property of the transformed PLK system also implies the monostationarity property of the original PYK system.

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The fundamental decomposition of a chemical reaction network (also called its $mathscr{F}$-decomposition) is the set of subnetworks generated by the partition of its set of reactions into the fundamental classes introduced by Ji and Feinberg in 2011 as the basis of their higher deficiency algorithm for mass action systems. The first part of this paper studies the properties of the $mathscr{F}$-decomposition, in particular, its independence (i.e., the networks stoichiometric subspace is the direct sum of the subnetworks stoichiometric subspaces) and its incidence-independence (i.e., the image of the networks incidence map is the direct sum of the incidence maps images of the subnetworks). We derive necessary and sufficient conditions for these properties and identify network classes where the $mathscr{F}$-decomposition coincides with other known decompositions. The second part of the paper applies the above-mentioned results to improve the Multistationarity Algorithm for power-law kinetic systems (MSA), a general computational approach that we introduced in previous work. We show that for systems with non-reactant determined interactions but with an independent $mathscr{F}$-decomposition, the transformation to a dynamically equivalent system with reactant-determined interactions -- required in the original MSA -- is not necessary. We illustrate this improvement with the subnetwork of Schmitzs carbon cycle model recently analyzed by Fortun et al.
There have been recent theoretic results that provide sufficient conditions for the existence of a species displaying absolute concentration robustness (ACR) in a power law kinetic (PLK) system. One such result involves the detection of ACR among networks of high deficiency by considering a lower deficiency subnetwork with ACR as a local property. In turn, this smaller subnetwork serves as a building block for the larger ACR-possessing network. Here, with this theorem as foundation, we construct an algorithm that systematically checks ACR in a PLK system. By slightly modifying the algorithm, we also provide a procedure that identifies balanced concentration robustness (BCR), a weaker form of concentration robustness than ACR, in a PLK system.
We provide a short supplement to the paper MAPK networks and their capacity for multistationarity due to toric steady states by Perez Millan and Turjanski. We show that the capacity for toric steady states in the three networks analyzed in that paper can be derived using the process of network translation, which corresponds the original mass action system to a generalized mass action system with the same steady states. In all three cases, the translated chemical reaction network is proper, weakly reversible, and has both a structural and kinetic deficiency of zero. This is sufficient to guarantee toric steady states by previously established work on network translations. A basis of the steady state ideal is then derived by consideration of the linkage classes of the translated chemical reaction network.
A complex balanced kinetic system is absolutely complex balanced (ACB) if every positive equilibrium is complex balanced. Two results on absolute complex balancing were foundational for modern chemical reaction network theory (CRNT): in 1972, M. Feinberg proved that any deficiency zero complex balanced system is absolutely complex balanced. In the same year, F. Horn and R. Jackson showed that the (full) converse of the result is not true: any complex balanced mass action system, regardless of its deficiency, is absolutely complex balanced. In this paper, we revive the study of ACB systems first by providing a partial converse to Feinbergs Theorem. In the spirit of Horn and Jacksons result, we then describe several methods for constructing new classes of ACB systems with positive deficiency and present classes of power law kinetic systems for each method. Furthermore, we illustrate the usefulness of the ACB property for obtaining new results on absolute concentration robustness (ACR) in a species, a concept introduced for mass action systems by Shinar and Feinberg in 2010, for a class of power law systems. Finally, we motivate the study of ACB in poly-PL systems, i.e. sums of power law systems, and indicate initial results.
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.
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