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 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 - Individual channel file: contain the formulation for calculating each channel's current - Channel gating formulation files, if applicable - General parameter file, containing all parameter values used in this model - Channel-specific parameter file, if present - Units definition file: unit 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 `_ 2. :math:`I_CaL` : `Calcium current model `_ 3. :math:`I_Kr` : `Rapid delayed rectifier potassium current model `_ 4. :math:`I_to` : `Transient outward potassium current model `_ 5. :math:`I_Ks` : `Slow delayed rectifier potassium current model `_ 6. :math:`I_f` : `Pacemaker/funny current model `_ 7. :math:`I_{K1}` : `Inward rectifier potassium current model `_ 8. Calcium Analysis : `Calcium handling in the iPSC-CM baseline model `_ 9. Whole cell model: `Whole cell model which includes all currents in order to generate action potentials `_ 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/