Journal of Theoretical Biology最新文献_第2页

Stably encoding phylogenetic trees with folios of leaf addresses 稳定地编码具有叶位对开的系统发育树。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-16 DOI: 10.1016/j.jtbi.2025.112265

Mark M. Tanaka , Ruiting Lan , Andrew R. Francis

{"title":"Stably encoding phylogenetic trees with folios of leaf addresses","authors":"Mark M. Tanaka , Ruiting Lan , Andrew R. Francis","doi":"10.1016/j.jtbi.2025.112265","DOIUrl":"10.1016/j.jtbi.2025.112265","url":null,"abstract":"<div><div>As genome sequencing data continue to expand, a persistent research challenge is to accommodate the growth of a phylogeny. This situation arises in molecular epidemiology, for example, where new taxonomic groups can appear in real time as pathogen isolates are sequenced. Efficient computational methods have been developed to place new leaves in existing trees, which removes the need to reconstruct trees from scratch. But for these tree extensions to be fully integrated with classification schemes requires a stable encoding of trees that keeps existing tree structures intact as new branches appear. Here, we propose a tree encoding, which we call a <em>folio</em>, that records the path from a reference vertex to each leaf, giving each leaf an <em>address</em>. We present a simple set of rules to assign new addresses to added leaves. The encoding is stable in the sense that it does not change as further leaf addresses are added to the folio. The tree can be uniquely recovered from a folio of addresses. We illustrate the methods using <em>Salmonella</em> genome data. Due to the properties of our encoding framework, we anticipate that it can be used for a range of different phylogenetic analyses.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112265"},"PeriodicalIF":2.0,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145088414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Modelling phylogeny in 16S rRNA gene sequencing datasets using string-based kernels 基于字符串核的16S rRNA基因测序数据集系统发育建模。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-12 DOI: 10.1016/j.jtbi.2025.112249

Jonathan Ish-Horowicz , Sarah Filippi

{"title":"Modelling phylogeny in 16S rRNA gene sequencing datasets using string-based kernels","authors":"Jonathan Ish-Horowicz , Sarah Filippi","doi":"10.1016/j.jtbi.2025.112249","DOIUrl":"10.1016/j.jtbi.2025.112249","url":null,"abstract":"<div><div>The bacterial microbiome is increasingly being recognised as a key factor in human health, driven in large part by datasets collected using 16S rRNA (ribosomal ribonucleic acid) gene sequencing, which enable cost-effective quantification of the composition of an individual’s bacterial community. One of the defining characteristics of 16S rRNA datasets is the evolutionary relationships that exist between taxa (phylogeny). Here, we demonstrate the utility of modelling these phylogenetic relationships in two statistical tasks (the two sample test and host trait prediction) and propose a novel family of kernels for analysing microbiome datasets by leveraging string kernels from the natural language processing literature. We show via simulation studies that a kernel two-sample test using the proposed kernel is sensitive to the phylogenetic scale of the difference between the two populations. In a second set of simulations we also show how Gaussian process modelling with string kernels can infer the distribution of bacterial-host effects across the phylogenetic tree and apply this approach to a real host-trait prediction task. The results in the paper can be reproduced by running the code at <span><span>https://github.com/jonathanishhorowicz/modelling_phylogeny_in_16srrna_using_string_kernels</span><svg><path></path></svg></span>.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112249"},"PeriodicalIF":2.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066383","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Intracellular ISG-virus interactions determine viral infection severity and persistence 细胞内isg -病毒相互作用决定病毒感染的严重程度和持久性。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-12 DOI: 10.1016/j.jtbi.2025.112251

Anass Bouchnita , Vitaly Volpert

{"title":"Intracellular ISG-virus interactions determine viral infection severity and persistence","authors":"Anass Bouchnita , Vitaly Volpert","doi":"10.1016/j.jtbi.2025.112251","DOIUrl":"10.1016/j.jtbi.2025.112251","url":null,"abstract":"<div><div>In innate immune response, type I interferons (IFNs) activate interferon-stimulated genes (ISGs), which suppress viral replication and secretion at the intracellular level. Yet, how these ISG-virus interactions shape infection progression and severity remains poorly understood. Here, we introduce a new viral infection model that explicitly incorporates intracellular ISG-virus dynamics. It structures, for the first time, infected cells based on viral load and ISG expression which offers a computationally efficient and adaptable approach to integrating ISG-virus intracellular dynamics into viral kinetics frameworks. We validate this new approach using patient data for pre-alpha COVID-19 strain and an HIV, then we use it to study the impact of ISG-virus kinetics on viral infection severity and persistence. Our simulations reveal that increased ISG induction prolongs infection by suppressing type I IFN production in infected cells and preventing tissue cell depletion. We further show that effective ISG-mediated viral suppression is critical for controlling infection severity. Finally, the model predicts that moderate viral secretion optimizes viral load production. Overall, the developed framework offers a flexible and computationally efficient tool for exploring the impact of intracellular type I interferon signaling on viral infections. It can be easily adapted to specific diseases and extended with pharmacokinetics-pharmacodynamics models to identify key therapeutic targets for drug development.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112251"},"PeriodicalIF":2.0,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145066443","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A kinetic study of multi-substrate uniporters 多底物单转运体的动力学研究。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-09 DOI: 10.1016/j.jtbi.2025.112267

Ana S. de Pereda, Jihyun Park, Lily S. Cheung

{"title":"A kinetic study of multi-substrate uniporters","authors":"Ana S. de Pereda, Jihyun Park, Lily S. Cheung","doi":"10.1016/j.jtbi.2025.112267","DOIUrl":"10.1016/j.jtbi.2025.112267","url":null,"abstract":"<div><div>Transporters play key roles in regulating the movement of molecules into and out of cells. Uniporters, the simplest class of transporters, use facilitated diffusion to translocate molecules across membranes down their concentration gradient. This process can be affected by the presence of additional substrates in the intra- and extracellular environment, which can either increase the net transport rate of a molecule via trans acceleration or decrease it via competitive inhibition. In this study, we derived mathematical models to describe the net transport rate of uniporters in the presence of multiple extracellular substrates or inhibitors. Analyses of these models identified four possible states for the system when two substrates are present, with two states leading to trans acceleration and the other two states resulting in inhibition. Finally, we found that the relation between kinetic constants that controls the fraction of transporters in the inward-facing open state is responsible for these behaviors. Our theoretical results provide a mathematical framework for understanding the dynamic response of uniporters in the presence of multiple substrates and inhibitors, which could have implications for various processes, from nutrient utilization to metabolic engineering.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112267"},"PeriodicalIF":2.0,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145042514","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Phenomenological modeling of gene transcription by approximating cooperativity of transcription factors improves prediction and reduces complexity in gene regulatory network models 通过近似转录因子的协同性来建立基因转录的现象学模型，可以提高预测能力，降低基因调控网络模型的复杂性。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-07 DOI: 10.1016/j.jtbi.2025.112264

Thiruvickraman Jothiprakasam, Siddharth Jhunjhunwala

{"title":"Phenomenological modeling of gene transcription by approximating cooperativity of transcription factors improves prediction and reduces complexity in gene regulatory network models","authors":"Thiruvickraman Jothiprakasam, Siddharth Jhunjhunwala","doi":"10.1016/j.jtbi.2025.112264","DOIUrl":"10.1016/j.jtbi.2025.112264","url":null,"abstract":"<div><div>Several computational models are available for representing the gene expression process, with each having their advantages and disadvantages. Phenomenological models are widely used as they make appropriate simplifications that aim to find a middle ground between accuracy and complexity. The existing phenomenological models compete in terms of how the transcription initiation process is approximated, to achieve high accuracy while having the lowest complexity possible. However, most current models still suffer from high parameter complexity in the case of complex promoters. Herein, we formally derive a phenomenological approach to model RNA polymerase recruitment, stating approximations on cooperativity between transcription factors that are applicable to promoters requiring multifactorial input, which reduces parameter complexity. We then apply this method to biologically relevant networks of varying complexities to show that the approximations improved predictive ability compared to existing models. In summary, our reduced parameter model (RPM) had lower complexity while maintaining high accuracy, which leads to better scalability for complex networks.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112264"},"PeriodicalIF":2.0,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mathematical model suggests current CAR-macrophage dosage is efficient to low pre-infusion tumour burden but refractory to high tumour burden 数学模型表明，目前的car -巨噬细胞剂量对低输注前肿瘤负荷有效，但对高肿瘤负荷难以耐受。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-04 DOI: 10.1016/j.jtbi.2025.112263

Shilian Xu , Maoxuan Liu

{"title":"Mathematical model suggests current CAR-macrophage dosage is efficient to low pre-infusion tumour burden but refractory to high tumour burden","authors":"Shilian Xu , Maoxuan Liu","doi":"10.1016/j.jtbi.2025.112263","DOIUrl":"10.1016/j.jtbi.2025.112263","url":null,"abstract":"<div><div>Chimeric antigen receptor (CAR)-macrophage therapy is a promising approach for tumour treatment due to antigen-specific phagocytosis and tumour clearance. However, the precise impact of tumour burden, dose and dosing regimens on therapeutic outcomes remains poorly understood. We developed ordinary differential equation (ODE) mathematical modelling and utilised parameter inference to analyse <em>in vitro</em> FACS-based phagocytosis assay data testing CD19-positive Raji tumour cell against CAR-macrophage, and revealed that phagocytosing efficiency of CAR-macrophage increases but saturates as both Raji cell and CAR-macrophage concentrations increase. This interaction resulted in bistable Raji cell kinetics; specifically, within a particular range of CAR-macrophage concentration, low tumour burdens are effectively inhibited, while high tumour burdens remain refractory. Furthermore, our model predicted that CAR-macrophage dosages typically suggested by current clinical trials yield favourable therapeutic outcomes only when tumour burden is low. For split CAR-macrophage infusion with fixed total dosage, the first infusion with high CAR-macrophage dose delivers superior treatment outcomes. Finally, we identified alternative infusion regimens: five billion cells administered monthly for three months, or seven billion cells every two months for six months, can efficiently suppress Raji cell replication irrespective of tumour burden. Our findings highlight CAR-macrophage therapeutic outcomes are strongly influenced by both tumour burden and different dosing regimens. This work underscores that reducing tumour burden, increasing CAR-macrophage dose in the first infusion and prolonging CAR-macrophage persistence are key strategies for achieving durable responses.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112263"},"PeriodicalIF":2.0,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145008508","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Approximate Bayesian computation for Markovian binary trees in phylogenetics 系统发育中马尔可夫二叉树的近似贝叶斯计算。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-09-02 DOI: 10.1016/j.jtbi.2025.112246

Mingqi He , Sophie Hautphenne , Yao-ban Chan

{"title":"Approximate Bayesian computation for Markovian binary trees in phylogenetics","authors":"Mingqi He , Sophie Hautphenne , Yao-ban Chan","doi":"10.1016/j.jtbi.2025.112246","DOIUrl":"10.1016/j.jtbi.2025.112246","url":null,"abstract":"<div><div>Phylogenetic trees describe the relationships between species in the evolutionary process, and provide information about the rates of diversification. To understand the mechanisms behind macroevolution, we consider a class of multitype branching processes called Markovian binary trees (MBTs). MBTs allow for trait-based variation in diversification rates, and provide a flexible and realistic probabilistic model for phylogenetic trees. We develop an approximate Bayesian computation (ABC) scheme to infer the rates of MBT parameters by exploiting the information in the shapes of phylogenetic trees. We evaluate the accuracy of this inference method using simulation studies, and find that our method is able to detect variation in the diversification rates, with accuracy comparable to, and generally better than, likelihood-based methods. In an application to a real-life phylogeny of squamata, we reinforce conclusions drawn from earlier studies, in particular supporting the existence of ovi-/viviparity transitions in both directions. Our method demonstrates the potential for more complex models of evolution to be employed in phylogenetic inference, in conjunction with likelihood-free schemes.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112246"},"PeriodicalIF":2.0,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Drug dosing for cancer therapy: A stochastic model predictive control perspective 癌症治疗的药物剂量：一个随机模型预测控制的观点。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-08-31 DOI: 10.1016/j.jtbi.2025.112255

Andrés Hernández-Rivera , Pablo Velarde , Ascensión Zafra-Cabeza , José M. Maestre

引用次数: 0

Emergent microtubule properties in a model of filament turnover and nucleation 细丝周转和成核模型中的涌现微管特性。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-08-30 DOI: 10.1016/j.jtbi.2025.112254

Anna C. Nelson , Scott A. McKinley , Melissa M. Rolls , Maria-Veronica Ciocanel

{"title":"Emergent microtubule properties in a model of filament turnover and nucleation","authors":"Anna C. Nelson , Scott A. McKinley , Melissa M. Rolls , Maria-Veronica Ciocanel","doi":"10.1016/j.jtbi.2025.112254","DOIUrl":"10.1016/j.jtbi.2025.112254","url":null,"abstract":"<div><div>Microtubules (MTs) are dynamic protein filaments essential for intracellular organization and transport, particularly in long-lived cells such as neurons. The plus and minus ends of neuronal MTs switch between growth and shrinking phases, and the nucleation of new filaments is believed to be regulated in both healthy and injury conditions. We propose stochastic and deterministic mathematical models to investigate the impact of filament nucleation and length-regulation mechanisms on emergent properties such as MT lengths and numbers in living cells. We expand our stochastic continuous-time Markov chain model of filament dynamics to incorporate MT nucleation and capture realistic stochastic fluctuations in MT numbers and tubulin availability. We also propose a simplified partial differential equation (PDE) model, which allows for tractable analytical investigation into steady-state MT distributions under different nucleation and length-regulating mechanisms. We find that the stochastic and PDE modeling approaches show good agreement in MT length distributions, and that both MT nucleation and the catastrophe rate of large-length MTs regulate MT length distributions. In both frameworks, multiple mechanistic combinations achieve the same average MT length. The models proposed can predict parameter regimes where the system is scarce in tubulin, the building block of MTs, and suggest that low filament nucleation regimes are characterized by high variation in MT lengths, while high nucleation regimes drive high variation in MT numbers. These mathematical frameworks have the potential to improve our understanding of MT regulation in both healthy and injured neurons.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"616 ","pages":"Article 112254"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Extinction and persistence in a temperature-driven, stage-structured stochastic model of Dalbulus maidis dynamics with nonlinear density-dependent regulation 具有非线性密度依赖调节的黄菖蒲动力学的温度驱动、阶段结构随机模型中的灭绝和持续。

IF 2 4区数学

Journal of Theoretical Biology Pub Date : 2025-08-30 DOI: 10.1016/j.jtbi.2025.112256

F.E. Cornes , R.H. Barriga Rubio , M. Otero

{"title":"Extinction and persistence in a temperature-driven, stage-structured stochastic model of Dalbulus maidis dynamics with nonlinear density-dependent regulation","authors":"F.E. Cornes , R.H. Barriga Rubio , M. Otero","doi":"10.1016/j.jtbi.2025.112256","DOIUrl":"10.1016/j.jtbi.2025.112256","url":null,"abstract":"<div><div>We present an extension of a previously developed stochastic, stage-structured model of <em>Dalbulus maidis</em> (corn leafhopper), an important pest and vector in maize crops. The extended model introduces nonlinear density-dependent regulation on the nymphal stage, mediated by a carrying capacity that dynamically depends on the leaf area of maize plants. Both insect and host-plant dynamics are explicitly modeled, but the interaction is asymmetric, as the plant is not affected by the insect in the present formulation. Our main objective is to explore how the interplay between temperature-driven development and host-plant dynamics shapes the long-term behavior of the insect population, leading to either extinction or persistence. Using simulations parameterized with laboratory and field data, we analyze how temperature and maize development affect insect dynamics, and assess whether the model can reproduce observed abundance patterns under realistic conditions. This modeling framework provides a biologically grounded and flexible basis for future extensions, including pathogen transmission and bidirectional feedback between the maize and the insect.</div></div>","PeriodicalId":54763,"journal":{"name":"Journal of Theoretical Biology","volume":"615 ","pages":"Article 112256"},"PeriodicalIF":2.0,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144979347","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"数学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0