Cargando…

Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections

Mathematical models of biological systems must strike a balance between being sufficiently complex to capture important biological features, while being simple enough that they remain tractable through analysis or simulation. In this work, we rigorously explore how to balance these competing interes...

Descripción completa

Detalles Bibliográficos
Autores principales: Gevertz, Jana L., Wares, Joanna R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232816/
https://www.ncbi.nlm.nih.gov/pubmed/30510594
http://dx.doi.org/10.1155/2018/8760371
_version_ 1783370464293289984
author Gevertz, Jana L.
Wares, Joanna R.
author_facet Gevertz, Jana L.
Wares, Joanna R.
author_sort Gevertz, Jana L.
collection PubMed
description Mathematical models of biological systems must strike a balance between being sufficiently complex to capture important biological features, while being simple enough that they remain tractable through analysis or simulation. In this work, we rigorously explore how to balance these competing interests when modeling murine melanoma treatment with oncolytic viruses and dendritic cell injections. Previously, we developed a system of six ordinary differential equations containing fourteen parameters that well describes experimental data on the efficacy of these treatments. Here, we explore whether this previously developed model is the minimal model needed to accurately describe the data. Using a variety of techniques, including sensitivity analyses and a parameter sloppiness analysis, we find that our model can be reduced by one variable and three parameters and still give excellent fits to the data. We also argue that our model is not too simple to capture the dynamics of the data, and that the original and minimal models make similar predictions about the efficacy and robustness of protocols not considered in experiments. Reducing the model to its minimal form allows us to increase the tractability of the system in the face of parametric uncertainty.
format Online
Article
Text
id pubmed-6232816
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Hindawi
record_format MEDLINE/PubMed
spelling pubmed-62328162018-12-03 Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections Gevertz, Jana L. Wares, Joanna R. Comput Math Methods Med Research Article Mathematical models of biological systems must strike a balance between being sufficiently complex to capture important biological features, while being simple enough that they remain tractable through analysis or simulation. In this work, we rigorously explore how to balance these competing interests when modeling murine melanoma treatment with oncolytic viruses and dendritic cell injections. Previously, we developed a system of six ordinary differential equations containing fourteen parameters that well describes experimental data on the efficacy of these treatments. Here, we explore whether this previously developed model is the minimal model needed to accurately describe the data. Using a variety of techniques, including sensitivity analyses and a parameter sloppiness analysis, we find that our model can be reduced by one variable and three parameters and still give excellent fits to the data. We also argue that our model is not too simple to capture the dynamics of the data, and that the original and minimal models make similar predictions about the efficacy and robustness of protocols not considered in experiments. Reducing the model to its minimal form allows us to increase the tractability of the system in the face of parametric uncertainty. Hindawi 2018-10-30 /pmc/articles/PMC6232816/ /pubmed/30510594 http://dx.doi.org/10.1155/2018/8760371 Text en Copyright © 2018 Jana L. Gevertz and Joanna R. Wares. https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Gevertz, Jana L.
Wares, Joanna R.
Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections
title Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections
title_full Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections
title_fullStr Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections
title_full_unstemmed Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections
title_short Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections
title_sort developing a minimally structured mathematical model of cancer treatment with oncolytic viruses and dendritic cell injections
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232816/
https://www.ncbi.nlm.nih.gov/pubmed/30510594
http://dx.doi.org/10.1155/2018/8760371
work_keys_str_mv AT gevertzjanal developingaminimallystructuredmathematicalmodelofcancertreatmentwithoncolyticvirusesanddendriticcellinjections
AT waresjoannar developingaminimallystructuredmathematicalmodelofcancertreatmentwithoncolyticvirusesanddendriticcellinjections