Reproducibility of the computational model of induced pluripotent stem-cell derived cardiomyocytes

About this model

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.

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 (for instance: Current_Ik1)
• Channel gating formulation files, if applicable (for instance: gating_Ik1)
• General parameter file, containing all parameter values used in this model: parameter
• Channel-specific parameter file, if present (for instance: parameter_Ik1)
• 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. I_Na : Sodium current model
2. I_CaL : Calcium current model
3. I_Kr : Rapid delayed rectifier potassium current model
4. I_to : Transient outward potassium current model
5. I_Ks : Slow delayed rectifier potassium current model
6. I_f : Pacemaker/funny current model
7. 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.