arXiv subjects

Anne Shiu

Publications and source records attributed to Anne Shiu.

54 records · Page 3Linked to original sources

arXiv2016

Which small reaction networks are multistationary?

Reaction networks taken with mass-action kinetics arise in many settings, from epidemiology to population biology to systems of chemical reactions. Bistable reaction networks are posited to underlie biochemical switches, which motivates the following question: which reaction networks have the capacity for multiple steady states? Mathematically, this asks: among certain parametrized families of polynomial systems, which admit multiple positive roots? No complete answer is known. This work analyzes the smallest networks, those with only a few chemical species or reactions. For these "smallest" networks, we completely answer the question of multistationarity and, in some cases, multistability too, thereby extending related work of Boros. Our results highlight the role played by the Newton polytope of a network (the convex hull of the reactant vectors). Also, our work is motivated by recent results that explain how a given network's capacity for multistationarity arises from that of certain related networks which are typically smaller. Hence, we are interested in classifying small multistationary networks, and our work forms a first step in this direction.

math.DS↗

arXiv2016

Analyzing Multistationarity in Chemical Reaction Networks using the Determinant Optimization Method

Multistationary chemical reaction networks are of interest to scientists and mathematicians alike. While some criteria for multistationarity exist, obtaining explicit reaction rates and steady states that exhibit multistationarity for a given network -- in order to check nondegeneracy or determine stability of the steady states, for instance -- is nontrivial. Nonetheless, we accomplish this task for a certain family of sequestration networks. Additionally, our results allow us to prove the existence of nondegenerate steady states for some of these sequestration networks, thereby resolving a subcase of a conjecture of Joshi and Shiu. Our work relies on the determinant optimization method, developed by Craciun and Feinberg, for asserting that certain networks are multistationary. More precisely, we implement the construction of reaction rates and multiple steady states which appears in the proofs that underlie their method. Furthermore, we describe in detail the steps of this construction so that other researchers can more easily obtain, as we did, multistationary rates and steady states.

math.DS↗

arXiv2015

A survey of methods for deciding whether a reaction network is multistationary

Which reaction networks, when taken with mass-action kinetics, have the capacity for multiple steady states? There is no complete answer to this question, but over the last 40 years various criteria have been developed that can answer this question in certain cases. This work surveys these developments, with an emphasis on recent results that connect the capacity for multistationarity of one network to that of another. In this latter setting, we consider a network $N$ that is embedded in a larger network $G$, which means that $N$ is obtained from $G$ by removing some subsets of chemical species and reactions. This embedding relation is a significant generalization of the subnetwork relation. For arbitrary networks, it is not true that if $N$ is embedded in $G$, then the steady states of $N$ lift to $G$. Nonetheless, this does hold for certain classes of networks; one such class is that of fully open networks. This motivates the search for embedding-minimal multistationary networks: those networks which admit multiple steady states but no proper, embedded networks admit multiple steady states. We present results about such minimal networks, including several new constructions of infinite families of these networks.

math.DS↗

arXiv2014

Sign conditions for injectivity of generalized polynomial maps with applications to chemical reaction networks and real algebraic geometry

We give necessary and sufficient conditions in terms of sign vectors for the injectivity of families of polynomial maps with arbitrary real exponents defined on the positive orthant. Our work relates and extends existing injectivity conditions expressed in terms of Jacobian matrices and determinants. In the context of chemical reaction networks with power-law kinetics, our results can be used to preclude as well as to guarantee multiple positive steady states. In the context of real algebraic geometry,our work recognizes a prior result of Craciun, Garcia-Puente, and Sottile, together with work of two of the authors, as the first partial multivariate generalization of the classical Descartes' rule, which bounds the number of positive real roots of a univariate real polynomial in terms of the number of sign variations of its coefficients.

math.AG↗

arXiv2014

A global convergence result for processive multisite phosphorylation systems

Multisite phosphorylation plays an important role in intracellular signaling. There has been much recent work aimed at understanding the dynamics of such systems when the phosphorylation/dephosphorylation mechanism is distributive, that is, when the binding of a substrate and an enzyme molecule results in addition or removal of a single phosphate group and repeated binding therefore is required for multisite phosphorylation. In particular, such systems admit bistability. Here we analyze a different class of multisite systems, in which the binding of a substrate and an enzyme molecule results in addition or removal of phosphate groups at all phosphorylation sites. That is, we consider systems in which the mechanism is processive, rather than distributive. We show that in contrast with distributive systems, processive systems modeled with mass-action kinetics do not admit bistability and, moreover, exhibit rigid dynamics: each invariant set contains a unique equilibrium, which is a global attractor. Additionally, we obtain a monomial parametrization of the steady states. Our proofs rely on a technique of Johnston for using "translated" networks to study systems with "toric steady states", recently given sign conditions for injectivity of polynomial maps, and a result from monotone systems theory due to Angeli and Sontag.

q-bio.MN↗

arXiv2013

A geometric approach to the Global Attractor Conjecture

This paper introduces the class of "strongly endotactic networks", a subclass of the endotactic networks introduced by G. Craciun, F. Nazarov, and C. Pantea. The main result states that the global attractor conjecture holds for complex-balanced systems that are strongly endotactic: every trajectory with positive initial condition converges to the unique positive equilibrium allowed by conservation laws. This extends a recent result by D. F. Anderson for systems where the reaction diagram has only one linkage class (connected component). The results here are proved using differential inclusions, a setting that includes power-law systems. The key ideas include a perspective on reaction kinetics in terms of combinatorial geometry of reaction diagrams, a projection argument that enables analysis of a given system in terms of systems with lower dimension, and an extension of Birch's theorem, a well-known result about intersections of affine subspaces with manifolds parameterized by monomials.

math.DS↗

arXiv2013

A Projection Argument for Differential Inclusions, with Applications to Persistence of Mass-Action Kinetics

Motivated by questions in mass-action kinetics, we introduce the notion of vertexical family of differential inclusions. Defined on open hypercubes, these families are characterized by particular good behavior under projection maps. The motivating examples are certain families of reaction networks -- including reversible, weakly reversible, endotactic, and strongly endotactic reaction networks -- that give rise to vertexical families of mass-action differential inclusions. We prove that vertexical families are amenable to structural induction. Consequently, a trajectory of a vertexical family approaches the boundary if and only if either the trajectory approaches a vertex of the hypercube, or a trajectory in a lower-dimensional member of the family approaches the boundary. With this technology, we make progress on the global attractor conjecture, a central open problem concerning mass-action kinetics systems. Additionally, we phrase mass-action kinetics as a functor on reaction networks with variable rates.

math.DS↗

arXiv2012

Atoms of multistationarity in chemical reaction networks

Chemical reaction systems are dynamical systems that arise in chemical engineering and systems biology. In this work, we consider the question of whether the minimal (in a precise sense) multistationary chemical reaction networks, which we propose to call `atoms of multistationarity,' characterize the entire set of multistationary networks. Our main result states that the answer to this question is `yes' in the context of fully open continuous-flow stirred-tank reactors (CFSTRs), which are networks in which all chemical species take part in the inflow and outflow. In order to prove this result, we show that if a subnetwork admits multiple steady states, then these steady states can be lifted to a larger network, provided that the two networks share the same stoichiometric subspace. We also prove an analogous result when a smaller network is obtained from a larger network by `removing species.' Our results provide the mathematical foundation for a technique used by Siegal-Gaskins et al. of establishing bistability by way of `network ancestry.' Additionally, our work provides sufficient conditions for establishing multistationarity by way of atoms and moreover reduces the problem of classifying multistationary CFSTRs to that of cataloging atoms of multistationarity. As an application, we enumerate and classify all 386 bimolecular and reversible two-reaction networks. Of these, exactly 35 admit multiple positive steady states. Moreover, each admits a unique minimal multistationary subnetwork, and these subnetworks form a poset (with respect to the relation of `removing species') which has 11 minimal elements (the atoms of multistationarity).

math.DS↗

arXiv2012

Simplifying the Jacobian Criterion for precluding multistationarity in chemical reaction networks

Chemical reaction networks taken with mass-action kinetics are dynamical systems that arise in chemical engineering and systems biology. In general, determining whether a chemical reaction network admits multiple steady states is difficult, as this requires determining existence of multiple positive solutions to a large system of polynomials with unknown coefficients. However, in certain cases, various easy criteria can be applied. One such test is the Jacobian Criterion, due to Craciun and Feinberg, which gives sufficient conditions for ruling out the possibility of multiple steady states. A chemical reaction network is said to pass the Jacobian Criterion if all terms in the determinant expansion of its parametrized Jacobian matrix have the same sign. In this article, we present a procedure which simplifies the application of the Jacobian Criterion, and as a result, we identify a new class of networks for which multiple steady states is precluded: those in which all chemical species have total molecularity of at most two. The total molecularity of a species refers to the sum of all of its stoichiometric coefficients in the network. We illustrate our results by examining enzyme catalysis networks.

math.DS↗

arXiv2011

Chemical reaction systems with toric steady states

Mass-action chemical reaction systems are frequently used in Computational Biology. The corresponding polynomial dynamical systems are often large (consisting of tens or even hundreds of ordinary differential equations) and poorly parametrized (due to noisy measurement data and a small number of data points and repetitions). Therefore, it is often difficult to establish the existence of (positive) steady states or to determine whether more complicated phenomena such as multistationarity exist. If, however, the steady state ideal of the system is a binomial ideal, then we show that these questions can be answered easily. The focus of this work is on systems with this property, and we say that such systems have toric steady states. Our main result gives sufficient conditions for a chemical reaction system to have toric steady states. Furthermore, we analyze the capacity of such a system to exhibit positive steady states and multistationarity. Examples of systems with toric steady states include weakly-reversible zero-deficiency chemical reaction systems. An important application of our work concerns the networks that describe the multisite phosphorylation of a protein by a kinase/phosphatase pair in a sequential and distributive mechanism.

math.DS↗

arXiv2010

Siphons in chemical reaction networks

Siphons in a chemical reaction system are subsets of the species that have the potential of being absent in a steady state. We present a characterization of minimal siphons in terms of primary decomposition of binomial ideals, we explore the underlying geometry, and we demonstrate the effective computation of siphons using computer algebra software. This leads to a new method for determining whether given initial concentrations allow for various boundary steady states.

math.AC↗

arXiv2009

The dynamics of weakly reversible population processes near facets

This paper concerns the dynamical behavior of weakly reversible, deterministically modeled population processes near the facets (codimension-one faces) of their invariant manifolds and proves that the facets of such systems are "repelling." It has been conjectured that any population process whose network graph is weakly reversible (has strongly connected components) is persistent. We prove this conjecture to be true for the subclass of weakly reversible systems for which only facets of the invariant manifold are associated with semilocking sets, or siphons. An important application of this work pertains to chemical reaction systems that are complex-balancing. For these systems it is known that within the interior of each invariant manifold there is a unique equilibrium. The Global Attractor Conjecture states that each of these equilibria is globally asymptotically stable relative to the interior of the invariant manifold in which it lies. Our results pertaining to weakly reversible systems imply that this conjecture holds for all complex-balancing systems whose boundary equilibria lie in the relative interior of the boundary facets. As a corollary, we show that the Global Attractor Conjecture holds for those systems for which the associated invariant manifolds are two-dimensional.

math.DS↗

arXiv2008

The smallest multistationary mass-preserving chemical reaction network

Biochemical models that exhibit bistability are of interest to biologists and mathematicians alike. Chemical reaction network theory can provide sufficient conditions for the existence of bistability, and on the other hand can rule out the possibility of multiple steady states. Understanding small networks is important because the existence of multiple steady states in a subnetwork of a biochemical model can sometimes be lifted to establish multistationarity in the larger network. This paper establishes the smallest reversible, mass-preserving network that admits bistability and determines the semi-algebraic set of parameters for which more than one steady state exists.

math.DS↗

arXiv2008

Convex Rank Tests and Semigraphoids

Convex rank tests are partitions of the symmetric group which have desirable geometric properties. The statistical tests defined by such partitions involve counting all permutations in the equivalence classes. Each class consists of the linear extensions of a partially ordered set specified by data. Our methods refine existing rank tests of non-parametric statistics, such as the sign test and the runs test, and are useful for exploratory analysis of ordinal data. We establish a bijection between convex rank tests and probabilistic conditional independence structures known as semigraphoids. The subclass of submodular rank tests is derived from faces of the cone of submodular functions, or from Minkowski summands of the permutohedron. We enumerate all small instances of such rank tests. Of particular interest are graphical tests, which correspond to both graphical models and to graph associahedra.

math.CO↗

arXiv2007

Toric dynamical systems

Toric dynamical systems are known as complex balancing mass action systems in the mathematical chemistry literature, where many of their remarkable properties have been established. They include as special cases all deficiency zero systems and all detailed balancing systems. One feature is that the steady state locus of a toric dynamical system is a toric variety, which has a unique point within each invariant polyhedron. We develop the basic theory of toric dynamical systems in the context of computational algebraic geometry and show that the associated moduli space is also a toric variety. It is conjectured that the complex balancing state is a global attractor. We prove this for detailed balancing systems whose invariant polyhedron is two-dimensional and bounded.

math.DS↗

arXiv2007

The Cyclohedron Test for Finding Periodic Genes in Time Course Expression Studies

The problem of finding periodically expressed genes from time course microarray experiments is at the center of numerous efforts to identify the molecular components of biological clocks. We present a new approach to this problem based on the cyclohedron test, which is a rank test inspired by recent advances in algebraic combinatorics. The test has the advantage of being robust to measurement errors, and can be used to ascertain the significance of top-ranked genes. We apply the test to recently published measurements of gene expression during mouse somitogenesis and find 32 genes that collectively are significant. Among these are previously identified periodic genes involved in the Notch/FGF and Wnt signaling pathways, as well as novel candidate genes that may play a role in regulating the segmentation clock. These results confirm that there are an abundance of exceptionally periodic genes expressed during somitogenesis. The emphasis of this paper is on the statistics and combinatorics that underlie the cyclohedron test and its implementation within a multiple testing framework.

q-bio.QM↗

arXiv2006

Three Counterexamples on Semigraphoids

Semigraphoids are combinatorial structures that arise in statistical learning theory. They are equivalent to convex rank tests and to polyhedral fans that coarsen the reflection arrangement of the symmetric group. We resolve two problems on semigraphoids posed in Studeny's book, and we answer a related question by Postnikov, Reiner, and Williams on generalized permutohedra. We also study the semigroup and the toric ideal associated with semigraphoids.

math.CO↗

arXiv2006

Geometry of rank tests

We study partitions of the symmetric group which have desirable geometric properties. The statistical tests defined by such partitions involve counting all permutations in the equivalence classes. These permutations are the linear extensions of partially ordered sets specified by the data. Our methods refine rank tests of non-parametric statistics, such as the sign test and the runs test, and are useful for the exploratory analysis of ordinal data. Convex rank tests correspond to probabilistic conditional independence structures known as semi-graphoids. Submodular rank tests are classified by the faces of the cone of submodular functions, or by Minkowski summands of the permutohedron. We enumerate all small instances of such rank tests. Graphical tests correspond to both graphical models and to graph associahedra, and they have excellent statistical and algorithmic properties.

math.ST↗