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PCABM_ADT

Model used in the paper 'Agent-based modeling of the prostate tumor microenvironment uncovers spatial tumor growth constraints and immunomodulatory properties' by MNG van Genderen et. al. https://doi.org/10.1038/s41540-024-00344-6

Main Folder

The main folder contains examples of how to run and use PCABM.

ABM_run Example of how to run a simple simulation of PCABM. Function getHyperParameters determines which set of parameter is used (with or without R1881 or castration resistance).

ABM_CRPC_variation Run CRPC growth in the TME with different defined ratios of cells.

ABM_CRPC_spontaneous Run 'spontaneous' development of CRPC in the TME. This simulation contains a 'full' cycle of PCa growth. Starting with growth in R1881, moving to DMSO (castration) and eventually growth of resistant cells in DMSO. Resistant tumor cells develop spontaneously upon proliferation of non-resistant cells with probability TUpres.

Subroutines_ABM

Contains all files to run the prostate cancer agent based model (PCABM). Model was based on ABM for CRC by Jakob Nikolas Kather et al. (2017) PCABM was adapted to be more prostate cancer specific and contains tumor cells, fibroblast, M1 and M2 type macrophages. For detailed explenation on interactions between cell types, please see project report.

growTumor is the main function that bundles all other functions and runs all parts.

getHyperParameters Get parameters for condition with R1881, DMSO, CRPC, or LNCaP-abl only in DMSO

getSystemParamters Get all general parameters Although not used in project report - tumor cells can posibly be stem cells (set parameter TUps to non-zero in getSystemParams.m).

getAdjacent Get cell neighborhood

shuffleCells Randomly order vector of cells

TU_go_grow_die Function for modeling tumor cell migration, growth and death.

F_go_grow_die Function for modeling firoblast growth and migration

mCellRound Function for modeling macrophage round/behavior. Combines all seperate macrophages functions.

M_go Function for modeling macrophage migration

M_go_die Function for modeling macropahge migration & death

M_kill Function for modeling macropahge killing of tumor cells

M_promote NOT USED: Model macrophages promoting tumor cells, but only for tumor cells close to the macrophage. Could be added/replaced in mCellRound in future use.

updateSystem Function to update sytem in each time step (iteration) after all cells performed their round of actions.

visualizeSystem Function to visualize simulation

writeMyVideo Function to write visulized simulation to video file

Functions

Contains functions for optimizing parameters and visualizing outputs of PCABM.

ABM_PSO_function Function that runs particle swarm optimization (PSO). PSO fits parameters by comparing best Mean Squared Error (MSE) between Relative Tumor Cell Numbers from Incucyte data to model output for each fit.

MSE Objective function for PSO: the MSE.

shadedErrorBar Function by Rob Campbell - November 2009, for plotting shaded errobar lineplots.

Acknowledgements

Part of the code is adapted from a model by Kather et. al. (2017) http://dx.doi.org/10.5281/zenodo.853342

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