Identifiability investigation of within-host models of acute virus infection DOI Creative Commons

Yuganthi R. Liyanage,

Nora Heitzman-Breen, Necibe Tuncer

et al.

Mathematical Biosciences & Engineering, Journal Year: 2024, Volume and Issue: 21(10), P. 7394 - 7420

Published: Jan. 1, 2024

<p>Uncertainty in parameter estimates from fitting within-host models to empirical data limits the model's ability uncover mechanisms of infection, disease progression, and guide pharmaceutical interventions. Understanding effect model structure availability on predictions is important for informing development experimental design. To address sources uncertainty estimation, we used four mathematical influenza A infection with increased degrees biological realism. We tested each reveal its parameters presence unlimited by performing structural identifiability analyses. then refined results predicting practical under daily virus titers alone or together adaptive immune cell data. Using these approaches, presented insight into estimation provided guidelines types assumptions, optimal design, information needed improved predictions.</p>

Language: Английский

The effect of model structure and data availability on Usutu virus dynamics at three biological scales DOI Creative Commons
Nora Heitzman-Breen,

Yuganthi R. Liyanage,

Nisha K. Duggal

et al.

Royal Society Open Science, Journal Year: 2024, Volume and Issue: 11(2)

Published: Feb. 1, 2024

Understanding the epidemiology of emerging pathogens, such as Usutu virus (USUV) infections, requires systems investigation at each scale involved in host-virus transmission cycle, from individual bird to bird-to-vector transmissions, and USUV incidence vector populations. For new pathogens field data are sparse, predictions can be aided by use laboratory-type inoculation experiments combined with dynamical mathematical modelling. In this study, we investigated dynamics two strains constructing models for within-host scale, vector-borne epidemiological scale. We used infectious per cent mosquito infection predict birds mosquitoes. addressed dependence on model structure, uncertainty experimental design. found that one change predicted results another proposed

Language: Английский

Citations

9
Assessing the role of model choice in parameter identifiability of cancer treatment efficacy DOI Creative Commons

Nadine Kuehle Genannt Botmann,

Hana M. Dobrovolny

Frontiers in Applied Mathematics and Statistics, Journal Year: 2025, Volume and Issue: 11

Published: March 24, 2025

Several mathematical models are commonly used to describe cancer growth dynamics. Fitting of these experimental data has not yet determined which particular model best describes growth. Unfortunately, choice is known drastically alter the predictions both future tumor and effectiveness applied treatment. Since there growing interest in using help predict chemotherapy, we need determine if affects estimates chemotherapy efficacy. Here, simulate an vitro study by creating synthetic treatment each seven fit sets other (“wrong”) models. We estimate ε max (the maximum efficacy drug) IC 50 drug concentration at half effect achieved) effort whether use incorrect changes parameters. find that largely weakly practically identifiable no matter generate or data. The more likely be identifiable, but sensitive model, showing poor identifiability when Bertalanffy either

Language: Английский

Citations

0
Incorporating Intracellular Processes in Virus Dynamics Models DOI Creative Commons
Stanca M. Ciupe, Jessica M. Conway

Microorganisms, Journal Year: 2024, Volume and Issue: 12(5), P. 900 - 900

Published: April 30, 2024

In-host models have been essential for understanding the dynamics of virus infection inside an infected individual. When used together with biological data, they provide insight into viral life cycle, intracellular and cellular virus–host interactions, role, efficacy, mode action therapeutics. In this review, we present standard model highlight situations where added complexity accounting processes is needed. We several examples from acute chronic infections such inclusion in explicit implicit manner has led to improvement parameter estimates, unification conclusions, guidance targeted therapeutics, crossover among systems. also discuss trade-offs between realism predictive power need increased data collection at finer scale resolution better validate complex models.

Language: Английский

Citations

3
Identifiability investigation of within-host models of acute virus infection DOI Creative Commons

Yuganthi R. Liyanage,

Nora Heitzman-Breen, Necibe Tuncer

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: May 10, 2024

Abstract Uncertainty in parameter estimates from fitting within-host models to empirical data limits the model’s ability uncover mechanisms of infection, disease progression, and guide pharmaceutical interventions. Understanding effect model structure availability on predictions is important for informing development experimental design. To address sources uncertainty estimation, we use four mathematical influenza A infection with increased degrees biological realism. We test each reveal its parameters presence unlimited by performing structural identifiability analyses. then refine results predicting practical under daily virus titers alone or together adaptive immune cell data. Using these approaches, present insight into estimation provide guidelines types assumptions, optimal design, information needed improved predictions. Author summary Within-host infections fitted have our understanding allowed us Given their predictive power, it essential that properly estimation. Here, focus unknown parameters. questions, analysis. insights estimations

Language: Английский

Citations

3
A novel within-host model of HIV and nutrition DOI Creative Commons

Archana Timsina,

Yuganthi R. Liyanage,

Maia Martcheva

et al.

Mathematical Biosciences & Engineering, Journal Year: 2024, Volume and Issue: 21(4), P. 5577 - 5603

Published: Jan. 1, 2024

<abstract><p>In this paper we develop a four compartment within-host model of nutrition and HIV. We show that the has two equilibria: an infection-free equilibrium infection equilibrium. The free is locally asymptotically stable when basic reproduction number $ \mathcal{R}_0 &lt; 1 $, unstable &gt; $. if additional condition holds. HIV structured to reveal its parameters from observations viral load, CD4 cell count total protein data. then estimate for these 3 data sets. have also studied practical identifiability by performing Monte Carlo simulations, found rate clearance virus immunoglobulins practically unidentifiable, rest are only weakly identifiable given experimental Furthermore, how frequency impacts parameters.</p></abstract>

Language: Английский

Citations

2
Validation of a Multi-Strain HIV Within-Host Model with AIDS Clinical Studies DOI Creative Commons
Necibe Tuncer, Kia Ghods, Vivek Sreejithkumar

et al.

Mathematics, Journal Year: 2024, Volume and Issue: 12(16), P. 2583 - 2583

Published: Aug. 21, 2024

We used a previously introduced HIV within-host model with sensitive and resistant strains validated it two data sets. The first set is from clinical study that investigated multi-drug treatments measured the total CD4+ cell count viral load. All nine patients in this experienced virologic failure. second includes unique patient who was treated drug for whom both were as well cells. studied structural identifiability of respect to each set. With set, structurally identifiable when production rate strain fixed distinct strain. always identifiable. fit using nonlinear mixed effect modeling Monolix estimated population-level parameters. inferred average time emergence 844 days after treatment starts. found out all parameters except mutation practically

Language: Английский

Citations

1
Usutu virus, an emerging arbovirus with One Health importance DOI
Sarah C. Kuchinsky, Nisha K. Duggal

Advances in virus research, Journal Year: 2024, Volume and Issue: unknown, P. 39 - 75

Published: Jan. 1, 2024

Language: Английский

Citations

1
A mathematical model for the role of vaccination and treatment in measles transmission in Turkey DOI
Osman Raşit Işık, Necibe Tuncer, Maia Martcheva

et al.

Journal of Computational and Applied Mathematics, Journal Year: 2024, Volume and Issue: 457, P. 116308 - 116308

Published: Oct. 11, 2024

Language: Английский

Citations

1
Identifiability investigation of within-host models of acute virus infection DOI Creative Commons

Yuganthi R. Liyanage,

Nora Heitzman-Breen, Necibe Tuncer

et al.

Mathematical Biosciences & Engineering, Journal Year: 2024, Volume and Issue: 21(10), P. 7394 - 7420

Published: Jan. 1, 2024

<p>Uncertainty in parameter estimates from fitting within-host models to empirical data limits the model's ability uncover mechanisms of infection, disease progression, and guide pharmaceutical interventions. Understanding effect model structure availability on predictions is important for informing development experimental design. To address sources uncertainty estimation, we used four mathematical influenza A infection with increased degrees biological realism. We tested each reveal its parameters presence unlimited by performing structural identifiability analyses. then refined results predicting practical under daily virus titers alone or together adaptive immune cell data. Using these approaches, presented insight into estimation provided guidelines types assumptions, optimal design, information needed improved predictions.</p>

Language: Английский

Citations

1