Virtual tumor manuscript

This GitHub repository contains all the files needed to reproduce the main outputs of the following manuscript (currently under submission in CPT:PSP):

QSP Modelling of tumor heterogeneity in response to BH3-mimetics using virtual tumors calibrated with cell viability assays

Thibaud Derippe, Sylvain Fouliard, Xavier Decleves, Donald E. Mager

Structure of the repository

The repository contains the following main R scripts:

• 0_Lindner_model_PaSM_config.R: includes the RxODE-formated modified Lindner model, along with PaSM configuration information (eg, monotonic parameter attribution),
• 1_1_Virtual_Cells_Generation.R uses PaSM algorithm to generate Virtual Cells and compute their fate (death or survival) under all 79 different drug exposure set-ups,
• 1_2_Rearrange_VC_files.R performs several manipulations with previously generated VCs, especially attributing them in 'bags', and selecting a single VC per bag depending on the number of drugs to consider. These celltheques/main outputs of the two VC scripts are directly provided in the folder 'Virtual_Cells/one_per_bag_combined' (other generated files were too voluminous to commit) for you can run the next scripts without the need to complete this step,
• 2_Virtual_Tumor_objects.R contains the main function to create, calibrate and evaluate/plot the virtual tumors (coded as R6 object). This script is not made to be manipulated, but used in the next one,
• 3_Virtual_Tumor_Calibration.R is the main script in which Virtual tumor are created and calibrated. The outputs of this script (the calibrated virtual tumors) are provided in the folder 'calibrated_VT',
• 4_agent_based_model_Fig6.R, 4_cell_composition_fig5.R and 4_other_figures_article_vt.R are the three scripts used to generate the manuscript's figures, including the heterogeneity analyses of the calibrated virtual tumors (fig5) and minimal-ABM attempts (fig 6). These 3 files are independent (no particular order to be used).

The three additional folders are:

• data contains the two datasets used in this work, namely the cell viability assays and the mice data, both digitized from two articles coming from D.C. Phillips et al (the two links above lead to the source articles).
• Virtual_Cells contains the final celltheques generated after using the scripts 1_1_Virtual_Cells_Generation.R and 1_2_Rearrange_VC_files.R
• calibrated_VT corresponds to the final outputs after using the script 3_Virtual_Tumor_Calibration.R

Contact

For any questions or issues with the code, feel free to contact me at Thibaud.Derippe@gmail.com. However, please note I do not work in the QSP field anymore, and therefore I do not intend to extend this work or improve the algorithms (unless needed for the manuscript itself).

Thanks !

Thibaud