- Author:
- Shelley Fong <sfon036@UoA.auckland.ac.nz>
- Date:
- 2024-09-27 09:52:37+12:00
- Desc:
- init
- Permanent Source URI:
- https://models.cellml.org/workspace/702/rawfile/841bbcd6641a430406471e20e4c7466aaea97112/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)
.. _CellML: https://www.cellml.org/
.. _OpenCOR: https://opencor.ws/
.. _GitHub: https://github.com/ClancyLabUCD/IPSC-model/
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/c63c733e2057d3e417439cf01363b411899eb53d/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/c63c733e2057d3e417439cf01363b411899eb53d/Current_Ik1.cellml>`_
- Channel gating formulation files, if applicable (for instance: `gating_Ik1) <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/gating_Ik1.cellml>`_
- General parameter file, containing all parameter values used in this model: `parameter <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/parameter.cellml>`_
- Channel-specific parameter file, if present (for instance: `parameter_Ik1) <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/parameter_Ik1.cellml>`_
- Units definition file: `unit <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/unit.cellml>`_
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 <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/Fig3_Na.py>`_
2. :math:`I_CaL` : `Calcium current model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig4_CaL.py>`_
3. :math:`I_Kr` : `Rapid delayed rectifier potassium current model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig5_Kr.py>`_
4. :math:`I_to` : `Transient outward potassium current model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig6_to.py>`_
5. :math:`I_Ks` : `Slow delayed rectifier potassium current model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig7_Ks.py>`_
6. :math:`I_f` : `Pacemaker/funny current model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/Fig8_f.py>`_
7. :math:`I_{K1}` : `Inward rectifier potassium current model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig9_K1.py>`_
8. Calcium Analysis : `Calcium handling in the iPSC-CM baseline model <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig10_Ca.py>`_
9. Whole cell model: `Whole cell model which includes all currents in order to generate action potentials <https://models.physiomeproject.org/workspace/702/file/c63c733e2057d3e417439cf01363b411899eb53d/fig11_wholecell.py>`_
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.
Each Python script under the Navigation menu reproduces a given
result 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_.
.. _`Kernik et al. (2019)`: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6767694/
