- Author:
- Shelley Fong <sfon036@UoA.auckland.ac.nz>
- Date:
- 2024-09-27 14:26:17+12:00
- Desc:
- Updating captions
- Permanent Source URI:
- https://models.fieldml.org/workspace/702/rawfile/013a1f6b66817f0be90630420f0c7fd83618cd18/RST/Overview.rst
About this model
*****************
:Original publication: `Kernik et al. (2019)`_:
"A computational model of induced pluripotent stem-cell derived cardiomyocytes
incorporating experimental variability from multiple data sources" J Physiol. 2019 Sep 1; 597(17): 4533-4564.
:DOI: https://dx.doi.org/10.1113%2FJP277724
Model status
**************
The current CellML model implementation runs in OpenCOR_.
Model overview
*****************
This workspace holds a CellML_ and Python encoding of the `Kernik et al. (2019)`_
model. The original model developed a whole cell model of
induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs)
composed of simple model components comprising ion channel models. The models were parameterized to fit experimental
iPSC-CM data from multiple laboratories for all major ionic currents.
.. figure:: figures/schematic-diagram.jpg
:width: 85%
:align: center
:alt: Schematics of the model
A diagrammatic representation of the `Kernik et al. (2019)`_ model. (Image from Fig 1 in the original paper)
Modular description
********************
CellML enables the user to divide a model
into distinct modules, which can be imported as needed.
The key CellML files of this work are:
- Main file: `Channels <https://models.physiomeproject.org/workspace/702/file/98f5f62a7e8d3e057f3d24027e38ed91a2a185ed/Channels.cellml>`_
- Individual channel file: contain the formulation for calculating each channel's current (for instance: `Current_Ik1) <https://models.physiomeproject.org/workspace/702/file/98f5f62a7e8d3e057f3d24027e38ed91a2a185ed/Current_Ik1.cellml>`_
- Channel gating formulation files, if applicable (for instance: `gating_Ik1) <https://models.physiomeproject.org/workspace/702/file/98f5f62a7e8d3e057f3d24027e38ed91a2a185ed/gating_Ik1.cellml>`_
- General parameter file, containing all parameter values used in this model: `parameter <https://models.physiomeproject.org/workspace/702/file/98f5f62a7e8d3e057f3d24027e38ed91a2a185ed/parameter.cellml>`_
- Channel-specific parameter file, if present (for instance: `parameter_Ik1) <https://models.physiomeproject.org/workspace/702/file/98f5f62a7e8d3e057f3d24027e38ed91a2a185ed/parameter_Ik1.cellml>`_
- Units definition file: `unit <https://models.physiomeproject.org/workspace/702/file/98f5f62a7e8d3e057f3d24027e38ed91a2a185ed/unit.cellml>`_
For each individual channel, Python is run to recreate the conditions outlined in `Kernik et al. (2019)`_, in order to reproduce the paper's figures. The file loads the SED-ML file and provides the simulation results. and plots the figure.
1. :math:`I_Na` : `Sodium current model <CellML/Current_Ina.cellml/view>`_
2. :math:`I_CaL` : `Calcium current model <CellML/Current_Ica.cellml/view>`_
3. :math:`I_Kr` : `Rapid delayed rectifier potassium current model <CellML/Current_Ikr.cellml/view>`_
4. :math:`I_to` : `Transient outward potassium current model <CellML/Current_Ito.cellml/view>`_
5. :math:`I_Ks` : `Slow delayed rectifier potassium current model <CellML/Current_Iks.cellml/view>`_
6. :math:`I_f` : `Pacemaker/funny current model <CellML/Current_If.cellml/view>`_
7. :math:`I_{K1}` : `Inward rectifier potassium current model <CellML/Current_Ik1.cellml/view>`_
8. Calcium Analysis : `Calcium handling in the iPSC-CM baseline model <RST/Fig10_Ca.rst/view>`_
9. Whole cell model: `Whole cell model which includes all currents in order to generate action potentials <RST/Fig11_wholecell.rst/view>`_
Simulation settings
*********************
The simulation settings are saved in SED-ML files, which are run through Python.
We use this method to capture the results for different initial conditions and inputs, corresponding to `Kernik et al. (2019)`_.
Each Python script under the Navigation menu reproduces the specified figure from `Kernik et al. (2019)`_.
The name of each scripts corresponds to the Figure number in the Kernik paper.
In order to run the scripts,
execute the following script from the command line:
``$ cd [PathToThisFile]``
``$ [PathToOpenCOR]/pythonshell fig2.py``
This action requires all files to be located within the same folder.
Model Origin
*******************
The original model of **induced pluripotent stem-cell derived cardiomyocytes incorporating
experimental variability from multiple data sources** was built in MATLAB and is available here_.
.. _CellML: https://www.cellml.org/
.. _OpenCOR: https://opencor.ws/
.. _here: https://github.com/ClancyLabUCD/IPSC-model/
.. _`Kernik et al. (2019)`: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767694/
