Uncovering the effects of heterogeneity and parameter sensitivity on within‑host dynamics of disease : malaria as a case study
Date
2021-07-24
Journal Title
Journal ISSN
Volume Title
Publisher
BMC (part of Springer Nature)
Abstract
Background: The fidelity and reliability of disease model predictions depend on accurate
and precise descriptions of processes and determination of parameters. Various
models exist to describe within-host dynamics during malaria infection but there is a
shortage of clinical data that can be used to quantitatively validate them and establish
confidence in their predictions. In addition, model parameters often contain a degree
of uncertainty and show variations between individuals, potentially undermining the
reliability of model predictions. In this study models were reproduced and analysed by
means of robustness, uncertainty, local sensitivity and local sensitivity robustness analysis
to establish confidence in their predictions.
Results: Components of the immune system are responsible for the most uncertainty
in model outputs, while disease associated variables showed the greatest sensitivity
for these components. All models showed a comparable degree of robustness but displayed
different ranges in their predictions. In these different ranges, sensitivities were
well-preserved in three of the four models.
Conclusion: Analyses of the effects of parameter variations in models can provide a
comparative tool for the evaluation of model predictions. In addition, it can assist in
uncovering model weak points and, in the case of disease models, be used to identify
possible points for therapeutic intervention.
Description
CITATION: Horn, S., Snoep, J. L. & Van Niekerk, D. D. 2021. Uncovering the effects of heterogeneity and parameter sensitivity on within‑host dynamics of disease: malaria as a case study. BMC Bioinformatics, 22:384, doi:10.1186/s12859-021-04289-z.
The original publication is available at https://bmcbioinformatics.biomedcentral.com
Publication of this article was funded by the Stellenbosch University Open Access Fund
The original publication is available at https://bmcbioinformatics.biomedcentral.com
Publication of this article was funded by the Stellenbosch University Open Access Fund
Keywords
Malaria, Malaria -- Models, Sensitivity analysis, Plasmodium -- Parasites, Modelling
Citation
Horn, S., Snoep, J. L. & Van Niekerk, D. D. 2021. Uncovering the effects of heterogeneity and parameter sensitivity on within‑host dynamics of disease: malaria as a case study. BMC Bioinformatics, 22:384, doi:10.1186/s12859-021-04289-z