PAM

This GitHub repository serves as documentation and reproduction source for the results published on bioRxiv. It contains the raw data, the data derived during the analysis, the model specifications (SBML format) and executable scripts (Jupyter notebooks).

Looking at the results

The results are documented by multiple notebooks, which contain interactive figures. To open the notebooks, please follow the links below:

In vitro study

1. Data pre-processing
2. Inference of K model
3. Inference of KP model
4. Inference of KR model
5. Prediction of treatment response for clinical dosing regimen

In silico study

1. Synthesis of measurements
2. Inference of K model after 10h experiment
3. Inference of K model after 15h experiment
4. Inference of K model after 20h experiment
5. Inference of K model after 30h experiment
6. Inference of KP model after 10h experiment
7. Inference of KP model after 15h experiment
8. Inference of KP model after 20h experiment
9. Inference of KP model after 30h experiment
10. Inference of KR model after 10h experiment
11. Inference of KR model after 15h experiment
12. Inference of KR model after 20h experiment
13. Inference of KR model after 30h experiment
14. Prediction of reduction doses

Reproduce results

We prepared two ways to reproduce our results: a non-programmer and a programmer way.

The easy way (no programming knowledge required)

You are welcome to re-run our scripts by clicking on the binder icon in the top right, once you have opened the notebook links above. By clicking on the notebook links, nbviewer renders the notebooks and provides a link to binder in the top right corner of the website (binder has an icon with three circles). By clicking on the binder icon, a server is started for you, and all dependencies for our scripts are installed automatically (this may take a couple seconds). Once this is done, you can run our scripts in the browser to reproduce the results.

The more flexible way (requires some knowledge of programming)

Alternatively, the GitHub repository can be cloned, and the scripts executed locally. For ease of execution, we prepared a Makefile that executes the scripts in the correct order. Please find a step-by-step instruction how the dependencies can be installed and the results be reproduced, once you have cloned the repostory.

1. Install dependencies

• 1.1 Install CVODE (myokit uses CVODE to solve ODEs)

For Ubuntu:

apt-get update && apt-get install libsundials-dev

For MacOS:

brew update-reset && brew install sundials

For Windows: No action required. Myokit installs CVODE automatically.

• 1.2 Install Python dependencies

pip install -r requirements.txt

2. Reproduce results

You can now reproduce the results by running

make all

This may take a while (30 mins or longer), because you are re-running all scripts sequentially. To reproduce only the in vitro study, or only the in silico study you can run

make in_vitro_study

or

make in_silico_study

Alternatively, you are welcome to run each script individually, but be aware that some scripts are dependent on the data derived in other scripts.