Gevertz2018 - cancer treatment with oncolytic viruses and dendritic cell injections minimal model

Model Identifier
BIOMD0000000817
Short description
The model is based on 'Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections', PMID:30510594. Author:Jana L.Gevertz and Joanna R.Wares. This model describes the minimal model described in section 2.1. Built by COPASI 4.24( Build 197)
Abstract:
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
SBML
(L3V1)
Related Publication
-
Developing a Minimally Structured Mathematical Model of Cancer Treatment with Oncolytic Viruses and Dendritic Cell Injections.
- Gevertz JL, Wares JR
- Computational and mathematical methods in medicine , 1/ 2018 , Volume 2018 , pages: 8760371 , PubMed ID: 30510594
- Department of Mathematics & Statistics, The College of New Jersey, Ewing, New Jersey, USA.
- 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.
Contributors
Submitter of the first revision: Szeyi Ng
Submitter of this revision: Szeyi Ng
Modellers: Szeyi Ng
Submitter of this revision: Szeyi Ng
Modellers: Szeyi Ng
Metadata information
is (2 statements)
isDescribedBy (1 statement)
hasTaxon (1 statement)
hasProperty (6 statements)
isDescribedBy (1 statement)
hasTaxon (1 statement)
hasProperty (6 statements)
Mathematical Modelling Ontology
Ordinary differential equation model
NCIt Oncolytic Virus Therapy
Human Disease Ontology melanoma
Experimental Factor Ontology cancer
Brenda Tissue Ontology B16-F10 cell
NCIt Oncolytic Virus Therapy
Human Disease Ontology melanoma
Experimental Factor Ontology cancer
Brenda Tissue Ontology B16-F10 cell
Curation status
Curated
Modelling approach(es)
Tags
Connected external resources
Name | Description | Size | Actions |
---|---|---|---|
Model files |
|||
model.xml | SBML L2V4 file for the model | 91.35 KB | Preview | Download |
Additional files |
|||
4b.png | Reproduced figure 4(b) | 8.42 KB | Preview | Download |
OV25.sedml | Sedml L1V2 file producing figure 4b with OV=2.5x10^9 | 1022.00 Bytes | Preview | Download |
OV25.xml | SBML L2V4 file for the model with OV=2.5x10^9 | 85.58 KB | Preview | Download |
OV5.sedml | Sedml L1V2 file producing figure 4b with OV=5x10^9 | 1022.00 Bytes | Preview | Download |
OV5.xml | SBML L2V4 file for the model with OV=5x10^9 | 85.58 KB | Preview | Download |
OVDC.cps | COPASI 4.24 (Build 197) file for the model with OV and DC treatment | 97.36 KB | Preview | Download |
OVDC.sedml | Sedml L1V2 file producing figure 4b with OV and DC treatment | 6.21 KB | Preview | Download |
- Model originally submitted by : Szeyi Ng
- Submitted: Sep 18, 2019 2:15:14 PM
- Last Modified: Sep 18, 2019 2:15:14 PM
Revisions
Legends
: Variable used inside SBML models
: Variable used inside SBML models
Species
Species | Initial Concentration/Amount |
---|---|
Uninfected Tumor Cell U cancer ; B16-F10 cell |
57.414042 mmol |
Dendritic Cells D dendritic cell ; Dendritic Cell |
0.0 mmol |
Oncolytic Adenovirus V Oncolytic ; Adenoviridae |
0.0 mmol |
Tumor targeting T cells T Natural Killer T-Cell ; Targeting |
0.0 mmol |
Infected Cancer Cell I B16-F10 cell ; cancer ; Abnormal |
0.0 mmol |
Reactions
Reactions | Rate | Parameters |
---|---|---|
Uninfected_Tumor_Cell_U => Infected_Cancer_Cell_I; Oncolytic_Adenovirus_V, Total_cells_N | compartment*beta*Uninfected_Tumor_Cell_U*Oncolytic_Adenovirus_V/Total_cells_N | beta = 1.008538 |
Dendritic_Cells_D => | compartment*delta_D*Dendritic_Cells_D | delta_D = 0.35 |
Oncolytic_Adenovirus_V => | compartment*delta_V*Oncolytic_Adenovirus_V | delta_V = 2.3 |
Tumor_targeting_T_cells_T => | compartment*delta_T*Tumor_targeting_T_cells_T | delta_T = 0.35 |
Uninfected_Tumor_Cell_U => ; Infected_Cancer_Cell_I, Tumor_targeting_T_cells_T, Total_cells_N | compartment*(k0+c_kill*Infected_Cancer_Cell_I)*Uninfected_Tumor_Cell_U*Tumor_targeting_T_cells_T/Total_cells_N | c_kill = 0.623397; k0 = 2.0 |
=> Oncolytic_Adenovirus_V | compartment*U_V | U_V = 0.0 |
=> Dendritic_Cells_D | compartment*U_D | U_D = 0.0 |
Infected_Cancer_Cell_I => | compartment*delta_I*Infected_Cancer_Cell_I | delta_I = 1.0 |
=> Tumor_targeting_T_cells_T; Infected_Cancer_Cell_I | compartment*C_T*Infected_Cancer_Cell_I | C_T = 1.428064 |
=> Tumor_targeting_T_cells_T; Dendritic_Cells_D | compartment*chi_D*Dendritic_Cells_D | chi_D = 4.901894 |
Curator's comment:
(added: 18 Sep 2019, 14:14:47, updated: 18 Sep 2019, 14:14:47)
(added: 18 Sep 2019, 14:14:47, updated: 18 Sep 2019, 14:14:47)
I reproduced figure 4(b) from the literature. I generated the data using COPASI 4.24(Build 197) and plot the graph using MATLAB.
The initial conditions and some other parameters are not indicated very clearly in the paper, I have contacted the author for further information. To view all the parameters, please refer to the attached files.