arXiv subjects

Nidhi Kaihnsa

Publications and source records attributed to Nidhi Kaihnsa.

12 recordsLinked to original sources

arXiv2026

Disconnectivity in Multistationarity Regions of Cascade of Goldbeter--Koshland Loops

Dynamics of reaction networks is often modelled by parameterised polynomials and describing the set of parameters for which the system attains multiple positive equilibrium states is a challenging problem. In the full parameter space, determined by the reaction rate constants and the total concentrations, the existing methods can give an upper bound on the number of connected components of regions that enable multistationarity and this can give sufficient condition to establish path connectivity of these regions. In this article, we focus on cascade network of Goldbeter-Koshland loops and show that for this network, with $n\geq 2$ phosphorylation sites and at least one shared phosphatase for dephosphorylation, the region in the space of reaction rates is connected while it may not be true in the full parameter space. We explicitly show that there is a gap between the upper and lower bound for the number of connected regions for the case when $n=2$.

q-bio.QM↗

arXiv2026

Algebraic Distance Optimization in Polyhedral Norms

We consider the distance minimization problem to a real algebraic variety $X \subseteq \RR^n$ when the metric is induced by a polyhedral norm. Each point in the variety has a Voronoi cell whose geometry depends on the normal space at the point and the inner normal fan of the polyhedral ball. For codimension-one varieties, we decompose $X$ into sets of points whose Voronoi cones have the same dimension, which is the expected dimension of their Voronoi cell. We prove that this decomposition is a stratification of $X$ and that each strata is a semialgebraic set. We conclude by giving an algebraic description of the medial axis, which is the locus of points whose minimal distance to $X$ is achieved at more than one point on $X$.

math.AG↗

arXiv2024

Connectivity of Parameter Regions of Multistationarity for Multisite Phosphorylation Networks

The parameter region of multistationarity of a reaction network contains all the parameters for which the associated dynamical system exhibits multiple steady states. Describing this region is challenging and remains an active area of research. In this paper, we concentrate on two biologically relevant families of reaction networks that model multisite phosphorylation and dephosphorylation of a substrate at $n$ sites. For small values of $n$, it had previously been shown that the parameter region of multistationarity is connected. Here, we extend these results and provide a proof that applies to all values of $n$. Our techniques are based on the study of the critical polynomial associated with these reaction networks together with polyhedral geometric conditions of the signed support of this polynomial.

q-bio.MN↗

arXiv2024

Network reduction and absence of Hopf Bifurcations in dual phosphorylation networks with three Intermediates

Phosphorylation networks, representing the mechanisms by which proteins are phosphorylated at one or multiple sites, are ubiquitous in cell signalling and display rich dynamics such as unlimited multistability. Dual-site phosphorylation networks are known to exhibit oscillations in the form of periodic trajectories, when phosphorylation and dephosphorylation occurs as a mixed mechanism: phosphorylation of the two sites requires one encounter of the kinase, while dephosphorylation of the two sites requires two encounters with the phosphatase. A still open question is whether a mechanism requiring two encounters for both phosphorylation and dephosphorylation also admits oscillations. In this work we provide evidence in favor of the absence of oscillations of this network by precluding Hopf bifurcations in any reduced network comprising three out of its four intermediate protein complexes. Our argument relies on a novel network reduction step that preserves the absence of Hopf bifurcations, and on a detailed analysis of the semi-algebraic conditions precluding Hopf bifurcations obtained from Hurwitz determinants of the characteristic polynomial of the Jacobian of the system. We conjecture that the removal of certain reverse reactions appearing in Michaelis-Menten-type mechanisms does not have an impact on the presence or absence of Hopf bifurcations. We prove an implication of the conjecture under certain favorable scenarios and support the conjecture with additional example-based evidence.

math.DS↗

arXiv2023

Absolute Concentration Robustness and Multistationarity in Reaction Networks: Conditions for Coexistence

Many reaction networks arising in applications are multistationary, that is, they have the capacity for more than one steady state; while some networks exhibit absolute concentration robustness (ACR), which means that some species concentration is the same at all steady states. Both multistationarity and ACR are significant in biological settings, but only recently has attention focused on the possibility for these properties to coexist. Our main result states that such coexistence in at-most-bimolecular networks (which encompass most networks arising in biology) requires at least $3$ species, $5$ complexes, and $3$ reactions. We prove additional bounds on the number of reactions for general networks based on the number of linear conservation laws. Finally, we prove that, outside of a few exceptional cases, ACR is equivalent to non-multistationarity for bimolecular networks that are small (more precisely, one-dimensional or up to two species). Our proofs involve analyses of systems of sparse polynomials, and we also use classical results from chemical reaction network theory.

math.DS↗

arXiv2023

Parameter region for multistationarity in $n-$site phosphorylation networks

Multisite phosphorylation is a signaling mechanism well known to give rise to multiple steady states, a property termed multistationarity. When phosphorylation occurs in a sequential and distributive manner, we obtain a family of networks indexed by the number of phosphorylation sites $n$. This work addresses the problem of understanding the parameter region where this family of networks displays multistationarity, by focusing on the projection of this region onto the set of kinetic parameters. The problem is phrased in the context of real algebraic geometry and reduced to studying whether a polynomial, defined as the determinant of a parametric matrix of size three, attains negative values over the positive orthant. The coefficients of the polynomial are functions of the kinetic parameters. For any $n$, we provide sufficient conditions for the polynomial to be positive and hence, preclude multistationarity, and also sufficient conditions for it to attain negative values and hence, enable multistationarity. These conditions are derived by exploiting the structure of the polynomial, its Newton polytope, and employing circuit polynomials. A relevant consequence of our results is that the set of kinetic parameters that enable or preclude multistationarity are both connected for all $n$.

q-bio.MN↗

arXiv2023

Prevalence of multistationarity and absolute concentration robustness in reaction networks

For reaction networks arising in systems biology, the capacity for two or more steady states, that is, multistationarity, is an important property that underlies biochemical switches. Another property receiving much attention recently is absolute concentration robustness (ACR), which means that some species concentration is the same at all positive steady states. In this work, we investigate the prevalence of each property while paying close attention to when the properties occur together. Specifically, we consider a stochastic block framework for generating random networks, and prove edge-probability thresholds at which - with high probability - multistationarity appears and ACR becomes rare. We also show that the small window in which both properties occur only appears in networks with many species. Taken together, our results confirm that, in random reversible networks, ACR and multistationarity together, or even ACR on its own, is highly atypical. Our proofs rely on two prior results, one pertaining to the prevalence of networks with deficiency zero, and the other "lifting" multistationarity from small networks to larger ones.

math.PR↗

arXiv2020

Coordinate-wise Powers of Algebraic Varieties

We introduce and study coordinate-wise powers of subvarieties of $\mathbb{P}^n$, i.e. varieties arising from raising all points in a given subvariety of $\mathbb{P}^n$ to the $r$-th power, coordinate by coordinate. This corresponds to studying the image of a subvariety of $\mathbb{P}^n$ under the quotient of $\mathbb{P}^n$ by the action of the finite group $\mathbb{Z}_r^{n+1}$. We determine the degree of coordinate-wise powers and study their defining equations, particularly for hypersurfaces and linear spaces. Applying these results, we compute the degree of the variety of orthostochastic matrices and determine iterated dual and reciprocal varieties of power sum hypersurfaces. We also establish a link between coordinate-wise squares of linear spaces and the study of real symmetric matrices with a degenerate eigenspectrum.

math.AG↗

arXiv2019

Cooperativity, Absolute Interaction, and Algebraic Optimization

We consider a measure of cooperativity based on the minimal absolute interaction required to generate an observed titration behavior. We describe the corresponding algebraic optimization problem and show how it can be solved using the nonlinear algebra tool \texttt{SCIP}. Moreover, we compute the minimal absolute interactions for various binding polynomials that describe the oxygen binding of various hemoglobins under different conditions. While calculated minimal absolute interactions are consistent with the expected outcome of the chemical modifications, it ranks the cooperativity of the molecules differently than the maximal Hill slope.

q-bio.BM↗

arXiv2019

Computing Convex Hulls of Trajectories

We study the convex hulls of trajectories of polynomial dynamical systems. Such trajectories include real algebraic curves. The boundaries of the resulting convex bodies are stratified into families of faces. We present numerical algorithms for identifying these patches. An implementation based on the software Bensolve Tools is given. This furnishes a key step in computing attainable regions of chemical reaction networks.

math.DS↗

arXiv2018

Attainable Regions of Dynamical Systems

We present a mathematical definition for the attainable region of a dynamical system, with primary focus on mass action kinetics for chemical reactions. We characterise this region for linear dynamical systems, and we report on experiments and conjectures for weakly reversible systems with linkage class one. A construction due to Vinzant is adapted to give a representation of faces in the convex hull of trajectories.

math.DS↗

arXiv2017

Sixty-Four Curves of Degree Six

We present a computational study of smooth curves of degree six in the real projective plane. In the Rokhlin-Nikulin classification, there are 56 topological types, refined into 64 rigid isotopy classes. We developed software that determines the topological type of a given sextic and used it to compute empirical probability distributions on the various types. We list 64 explicit representatives with integer coefficients, and we perturb these to draw many samples from each class. This allows us to explore how many of the bitangents, inflection points and tensor eigenvectors are real. We also study the real tensor rank, the construction of quartic surfaces with prescribed topology, and the avoidance locus, which is the locus of all real lines that do not meet a given sextic. This is a union of up to 46 convex regions, bounded by the dual curve.

math.AG↗