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

  public 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

Metadata information

is (2 statements)
BioModels Database BIOMD0000000817
BioModels Database MODEL1909180002

isDescribedBy (1 statement)
PubMed 30510594

hasTaxon (1 statement)
Taxonomy Mus musculus

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
Experimental Factor Ontology melanoma


Curation status
Curated



Connected external resources

SBGN view in Newt Editor

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
  • Version: 3 public model Download this version
    • Submitted on: Sep 18, 2019 2:15:14 PM
    • Submitted by: Szeyi Ng
    • With comment: Automatically added model identifier BIOMD0000000817
Legends
: 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)
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.