Journal of Theoretical Biology

The internal behaviour of a population is an important feature to take account of when modelling its dynamics. In line with kin selection theory, many social species tend to cluster into distinct groups in order to enhance their overall population fitness. Temporal interactions between populations are often modelled using classical mathematical models, but these sometimes fail to delve deeper into the, often uncertain, relationships within populations. Here, we introduce a stochastic framework that aims to capture the interactions of animal groups and an auxiliary population over time...

This paper revisits the observability and identifiability properties of a popular ODE model commonly adopted to characterize the HIV dynamics in HIV-infected patients with antiretroviral treatment. These properties are determined by using the general analytical solution of the unknown input observability problem, introduced very recently in Martinelli (2022). This solution provides the systematic procedures able to determine the state observability and the parameter identifiability of any ODE model, in particular, even in the presence of time varying parameters...

Our objective was to decompose mortality mechanisms during the coronavirus disease 2019 (COVID-19) pandemic to estimate direct, indirect, and associated deaths from COVID-19. Given the confirmatory diagnosis of COVID-19, a death event that was not necessarily caused by respiratory complications but stemmed from other complications was categorized as an indirect death from COVID-19. Associated deaths occurred in patients who did not have COVID-19 but died during the surge in COVID-19 cases when overwhelming pressure was exerted on the healthcare system...

Studies have shown that the internal structure of modules is hardly important for the spread of epidemics. However, most of these studies have assumed that intra-module connectivity and inter-module connectivity do not affect each other. In reality, changes in the internal structure of modules may affect inter-module links and thus change the modularity of the entire network. Therefore, we have developed a theoretical network model with adjustable modularity to investigate the impact of this situation on disease transmission...

This paper aims to present a comprehensive framework for coupling tumor-bone remodeling processes in a 2-dimensional geometry. This is achieved by introducing a bio-inspired damage that represents the growing tumor, which subsequently affects the main populations involved in the remodeling process, namely, osteoclasts, osteoblasts, and bone tissue. The model is constructed using a set of differential equations based on the Komarova's and Ayati's models, modified to incorporate the bio-inspired damage that may result in tumor mass formation...

Surface-feeding aquatic animals navigate towards the source of water disturbances and must differentiate prey from other environmental stimuli. Medicinal leeches locate prey, in part, using a distribution of mechanosensory hairs along their body that deflect under fluid flow. Leech's behavioral responses to surface wave temporal frequency are well documented. However, a surface wave's temporal frequency depends on many underlying environmental and fluid properties that vary substantially in natural habitats (e...

Oxygen (O2 ) regulated pathways modulate B cell activation, migration and proliferation during infection, vaccination, and other diseases. Modeling these pathways in health and disease is critical to understand B cell states and ways to mediate them. To characterize B cells by their activation of O2 regulated pathways we develop pathway specific discrete state models using previously published single-cell RNA-sequencing (scRNA-seq) datasets from isolated B cells...

In this note, we discuss the range of parameters for which the total quasi-steady-state approximation of the Michaelis-Menten reaction mechanism holds validity. We challenge the prevalent notion that total quasi-steady-state approximation is "roughly valid" across all parameters, showing that its validity cannot be assumed, even roughly, across the entire parameter space - when the initial substrate concentration is high. On the positive side, we show that the linearized one-dimensional equation for total substrate is a valid approximation when the initial reduced substrate concentration s0 /KM is small...

We developed a comprehensive mathematical model of cancer immunotherapy that takes into account: i) Immune checkpoint blockers (ICBs) and the interactions between cancer cells and the immune system, ii) characteristics of the tumor microenvironment, such as the tumor hydraulic conductivity, interstitial fluid pressure, and vascular permeability, iii) spatial and temporal variations of the modeled components within the tumor and the surrounding host tissue, iv) the transport of modeled components through the vasculature and between the tumor-host tissue with convection and diffusion, and v) modeling of the tumor draining lymph nodes were the antigen presentation and the development of cytotoxic immune cells take place...

Some viruses exhibit "rebound" when the administration of antiviral drugs is discontinued. Viral rebound caused by resistance mutations or latent reservoirs has been studied mathematically. In this study, we investigated the viral rebound due to other causes. Since immunity is weaker during antiviral treatment than without the treatment, drug discontinuation may lead to an increase in the viral load. We analyzed the dynamics of the number of virus-infected cells, cytotoxic T lymphocytes, and memory cells and identified the conditions under which the viral load increased upon drug discontinuation...

Complete synchronization among the metacommunity is known to elevate the risk of their extinction due to stochasticity and other environmental perturbations. Owing to the inherent heterogeneous nature of the metacommunity, we demonstrate the emergence of generalized synchronization among the patches of dispersally connected tritrophic food web using the framework of an auxiliary system approach and the mutual false nearest neighbor. We find that the critical value of the dispersal rate increases significantly with the size of the metacommunity for both unidirectional and bidirectional dispersals, which in turn corroborates that larger metacommunities are more stable than smaller ones...

Multivariate count distributions are crucial for the inference of ecological processes underpinning biodiversity. In particular, neutral theory provides useful null distributions allowing the evaluation of adaptation or natural selection. In this paper, we build a broader family of multivariate distributions: the Polya-splitting distributions. We show that they emerge naturally as stationary distributions of a multivariate birth-death process. This family of distributions is a consistent extension of non-zero sum neutral models based on a master equation approach...

We describe a cell-based fixed-lattice model to simulate immune cell and tumor cell interaction involving MHC recognition, and FasL vs perforin lysis. We are motivated by open questions about the mechanisms behind observed kill rates of tumor cells by different types of effector cells. These mechanisms play a big role in the effectiveness of many cancer immunotherapies. The model is a stochastic cellular automaton on a hexagonal grid.

BACKGROUND: Stent implantation is a highly efficacious intervention for the treatment of coronary atherosclerosis. Nevertheless, stent thrombosis and other post-operative complications persist, and the underlying mechanism of adverse event remains elusive. METHODS: In the present study, a dissipative particle dynamics model was formulated to simulate the motion, adhesion, activation, and aggregation of platelets, with the aim of elucidating the mechanisms of in-stent thrombosis...

BACKGROUND: Factor X activation by the phospholipid-bound intrinsic tenase complex is a critical membrane-dependent reaction of blood coagulation. Its regulation mechanisms are unclear, and a number of questions regarding diffusional limitation, pathways of assembly and substrate delivery remain open. METHODS: We develop and analyze here a detailed mechanism-driven computer model of intrinsic tenase on phospholipid surfaces. Three-dimensional reaction-diffusion-advection and stochastic simulations were used where appropriate...

Boolean modeling is a mathematical modeling framework used for defining and studying gene-regulatory networks (GRNs). It serves as a means to develop mechanistic models, offering insights into the trajectories and dynamic properties of GRNs. In this review, I delve into seminal papers published in the Journal of Theoretical Biology that have spearheaded this field. Additionally, I explore the application of these modeling methods in the current era of data-intensive science.

The dominant paradigm for modeling the obesity-induced T2DM (type 2 diabetes mellitus) today focuses on glucose and insulin regulatory systems, diabetes pathways, and diagnostic test evaluations. The problem with this approach is that it is not possible to explicitly account for the glucose transport mechanism from the blood to the liver, where the glucose is stored, and from the liver to the blood. This makes it inaccurate, if not incorrect, to properly model the concentration of glucose in the blood in comparison to actual glycated hemoglobin (A1C) test results...

OBJECTIVE: Owing to the heterogeneity in the evolution of cancer, distinguishing between diverse growth patterns and predicting long-term outcomes based on short-term measurements poses a great challenge. METHODS: A novel multiscale framework is proposed to unravel the connections between the population dynamics of cancer growth (i.e., aggressive, bounded, and indolent) and the cellular-subclonal dynamics of cancer evolution. This framework employs the non-negative lasso (NN-LASSO) algorithm to forge a link between an ordinary differential equation (ODE)-based population model and a cellular evolution model...

Many-to-many mapping of form-to-function posits that multiple morphological and physiological traits affect the performance of multiple tasks in an organism, and that redundancy and multitasking occur simultaneously to shape the evolution of an organism's phenotype. Many-to-many mapping is expected to be ubiquitous in nature, yet little is known about how it influences the evolution of organismal phenotype. The F-matrix is a powerful tool to study these issues because it describes how multiple traits affect multiple tasks...

We construct a multi-stage cell lineage model for cell division, apoptosis and movement. Cells are assumed to secrete and respond to negative feedback molecules which act as a control on the stem cell divisions (including self-renewal, asymmetrical cell division (ACD) and differentiation). The densities of cells and molecules are described by coupled reaction-diffusion partial differential equations, and the plane wavefront propagation speeds can be obtained analytically and verified numerically. It is found that with ACD the population and propagation of stem cells can be promoted but the negative regulation on self-renewal and differentiation will work slowly...