arXiv subjects

Hye-Won Kang

Publications and source records attributed to Hye-Won Kang.

7 recordsLinked to original sources

arXiv2026

Stochastic Averaging and Statistical Inference of Glycolytic Pathway

Many biological processes exhibit oscillatory behavior. Among these, glycolytic oscillations have been extensively studied due to their well-characterized biochemical reaction networks. However, the complexity of these networks necessitates low-dimensional ordinary differential equation (ODE) models to identify core mechanisms and perform stability analysis. While previous studies proposed reduced ODE models, these were typically introduced from deterministic descriptions rather than the underlying stochastic dynamics, which more accurately represent discrete reaction events occurring at random times. In this paper, we develop a rigorous probabilistic framework for deriving a reduced Othmer-Aldridge model of the glycolytic pathway from its stochastic formulation. The full system is modeled as a multiscale continuous-time Markov chain with different time and abundance scales. Under an appropriate scaling regime and specific structural conditions, we prove that the dynamics of the slow components are approximated by a two-dimensional ODE. The proof is technically involved due to the network's complexity and strong coupling between its components. We further consider the problem of parameter estimation when observations are limited to the slow species: fructose-6-phosphate and ADP. The reduced system yields a tractable loss function depending solely on these variables. We prove that the resulting estimators are statistically consistent when the data originate from the full stochastic reaction network. Together, these results provide a mathematically rigorous framework linking stochastic biochemical reaction networks, reduced deterministic dynamics, and statistically reliable parameter estimation.

math.PR↗

arXiv2023

Chemical systems with limit cycles

The dynamics of a chemical reaction network (CRN) is often modelled under the assumption of mass action kinetics by a system of ordinary differential equations (ODEs) with polynomial right-hand sides that describe the time evolution of concentrations of chemical species involved. Given an arbitrarily large integer $K \in {\mathbb N}$, we show that there exists a CRN such that its ODE model has at least $K$ stable limit cycles. Such a CRN can be constructed with reactions of at most second order provided that the number of chemical species grows linearly with $K$. Bounds on the minimal number of chemical species and the minimal number of chemical reactions are presented for CRNs with $K$ stable limit cycles and at most second order or seventh order kinetics. We also show that CRNs with only two chemical species can have $K$ stable limit cycles, when the order of chemical reactions grows linearly with $K$.

math.DS↗

arXiv2020

Incorporating age and delay into models for biophysical systems

In many biological systems, chemical reactions or changes in a physical state are assumed to occur instantaneously. For describing the dynamics of those systems, Markov models that require exponentially distributed inter-event times have been used widely. However, some biophysical processes such as gene transcription and translation are known to have a significant gap between the initiation and the completion of the processes, which renders the usual assumption of exponential distribution untenable. In this paper, we consider relaxing this assumption by incorporating age-dependent random time delays into the system dynamics. We do so by constructing a measure-valued Markov process on a more abstract state space, which allows us to keep track of the "ages" of molecules participating in a chemical reaction. We study the large-volume limit of such age-structured systems. We show that, when appropriately scaled, the stochastic system can be approximated by a system of Partial Differential Equations (PDEs) in the large-volume limit, as opposed to Ordinary Differential Equations (ODEs) in the classical theory. We show how the limiting PDE system can be used for the purpose of further model reductions and for devising efficient simulation algorithms. In order to describe the ideas, we use a simple transcription process as a running example. We, however, note that the methods developed in this paper apply to a wide class of biophysical systems.

q-bio.PE↗

arXiv2017

Quasi-steady-state approximations derived from the stochastic model of enzyme kinetics

In this paper we derive several quasi steady-state approximations (QSSAs) to the stochastic reaction network describing the Michaelis-Menten enzyme kinetics. We show how the different assumptions about chemical species abundance and reaction rates lead to the standard QSSA (sQSSA), the total QSSA (tQSSA), and the reverse QSSA (rQSSA) approximations. These three QSSAs have been widely studied in the literature in deterministic ordinary differential equation (ODE) settings and several sets of conditions for their validity have been proposed. By using multiscaling techniques introduced in Kang (and Kurtz 2013) and Ball et al. (2006) we show that these conditions for deterministic QSSAs largely agree with the ones for QSSAs in the large volume limits of the underlying stochastic enzyme kinetic network.

q-bio.MN↗

arXiv2017

Reduction for stochastic biochemical reaction networks with multiscale conservations

Biochemical reaction networks frequently consist of species evolving on multiple timescales. Stochastic simulations of such networks are often computationally challenging and therefore various methods have been developed to obtain sensible stochastic approximations on the timescale of interest. One of the rigorous and popular approaches is the multiscale approximation method for continuous time Markov processes. In this approach, by scaling species abundances and reaction rates, a family of processes parameterized by a scaling parameter is defined. The limiting process of this family is then used to approximate the original process. However, we find that such approximations become inaccurate when combinations of species with disparate abundances either constitute conservation laws or form virtual slow auxiliary species. To obtain more accurate approximation in such cases, we propose here an appropriate modification of the original method.

q-bio.MN↗

arXiv2014

Central limit theorems and diffusion approximations for multiscale Markov chain models

Ordinary differential equations obtained as limits of Markov processes appear in many settings. They may arise by scaling large systems, or by averaging rapidly fluctuating systems, or in systems involving multiple time-scales, by a combination of the two. Motivated by models with multiple time-scales arising in systems biology, we present a general approach to proving a central limit theorem capturing the fluctuations of the original model around the deterministic limit. The central limit theorem provides a method for deriving an appropriate diffusion (Langevin) approximation.

math.PR↗

arXiv2010

Separation of time-scales and model reduction for stochastic reaction networks

A stochastic model for a chemical reaction network is embedded in a one-parameter family of models with species numbers and rate constants scaled by powers of the parameter. A systematic approach is developed for determining appropriate choices of the exponents that can be applied to large complex networks. When the scaling implies subnetworks have different time-scales, the subnetworks can be approximated separately providing insight into the behavior of the full network through the analysis of these lower dimensional approximations.

math.PR↗