Strobl et al (2022). Spatial Structure Impacts Adaptive Therapy by Shaping Intra-Tumoral Competition

This repository contains the code and data for our publication Strobl et al (2022). Spatial Structure Impacts Adaptive Therapy by Shaping Intra-Tumoral Competition, Commun Med 2, 46, available here [1]. A pre-print of our manuscript is available on the bioRxiv [2].

Requirements

A full list of the Python packages used in this project can be found in requirements.txt. To recreate the virtual environment, run:

$ virtualenv <env_name>
$ source <env_name>/bin/activate
(<env_name>)$ pip install -r requirements.txt

For further details, see here

In addition, in order to create the neighbourhood plots (e.g. Figure 2d), you will require EvoFreq in R [3]. See the Github page for further instructions.

Computational model

The model is implemented in Java 1.8. in HAL [4]. The code can be found inside the abm/onLatticeCA directory:

• OnLatticeCA.java contains the main model class and simulation functions.
• Cell.java contains the class used to model individual cells in the model.
• runParameterSweep.java houses a wrapper that allows to run simulations from the command line. All data presented in the paper was collected using this wrapper.

All other files and directories inside abm/onLatticeCA are part of HAL, and were downloaded in their current form from HAL's Github repository. There are different ways to run the model. We recommend using the compiled onLatticeModel.jar executable, which was how we collected all the data presented in the manuscript. In fact, if you look at the jupyter notebooks (e.g. jnb_figure2.ipynb) you can see how you can run it directly from jupyter. Alternatively, you can run it from the command line by calling your java VM. An example of that may look as follows:

java -jar onLatticeModel.jar -initialSize 0.75 -rFrac 0.001 -turnover 0 -cost 0 -tEnd 3650 -seed 0 -nReplicates 1 -profilingMode false -terminateAtProgression true -imageOutDir ./data/exampleSims_noCost_noTurnover/images/ -imageFreq 10 -outDir ./data/scratch/

Finally, you can also compile and run the java code yourself. For instructions of how to do so, see the HAL manual (abm/manual.pdf).

Analysis

For each results figure in the manuscript we have created a separate jupyter notebook which houses the code to re-create this figure. These are named jnb_figure2.ipynb etc. and contain further explanations within.

In case of questions or comments, feel free to reach out to me at anytime.

References

• [1] Strobl, M. A. R., Gallaher, J., West, J., Robertson-Tessi, M., Maini, P. K., & Anderson, A. R. A. (2022). Spatial structure impacts adaptive therapy by shaping intra-tumoral competition. Communications Medicine, 2, 46, doi: https://rdcu.be/cL5bi.
• [2] Strobl, M. A. R., Gallaher, J., West, J., Robertson-Tessi, M., Maini, P. K., & Anderson, A. R. A. (2020). Spatial structure impacts adaptive therapy by shaping intra-tumoral competition. BioRxiv, 2020.11.03(365163), doi: https://doi.org/10.1101/2020.11.03.365163.
• [3] Gatenbee, C. D., Schenck, R. O., Bravo, R. R., & Anderson, A. R. A. (2019). EvoFreq: visualization of the Evolutionary Frequencies of sequence and model data. BMC Bioinformatics, 20(1), 710. https://doi.org/10.1186/s12859-019-3173-y
• [4] Bravo, R. R., Baratchart, E., West, J., Schenck, R. O., Miller, A. K., Gallaher, J., … Anderson, A. R. A. (2020). Hybrid Automata Library: A flexible platform for hybrid modeling with real-time visualization. PLoS Computational Biology, 16(3), e1007635. https://doi.org/10.1371/journal.pcbi.1007635