Modeling Responses to Kinase Inhibitor Combinations using Kinome Inhibition States

This repository contains code for processing kinobeads data for cell line response prediction to combination therapies, as outlined in the paper: https://pubmed.ncbi.nlm.nih.gov/38160286/

Prerequesites

This repository contains code written almost entirely in R, using Rstudio and 'Tidyverse' idioms. The file package_check.R describes all the R packages needed to run the code in a covenient "pacman" script. Running this script will install all the required packages in one go.

Repository Structure

This repository is divided into three main folders:

• src: source code for generating all results and figures
• data: raw data used by the source code (included in zenodo: 10.5281/zenodo.10680994)
• results: results generated by source code (included in zenodo: 10.5281/zenodo.10680994)
• figures: figures generated by source code

Data Organization

The folder src/data_organization contains code to process kinome profiling data from the kinobeads assay, and link it to cell line responses from NCI ALMANAC and baseline gene expression data from CCLE.

Modeling

The folder src/ALMANAC_klaeger_johnson_modelling contains code to build machine learning models using the combined dataset, predicting combination cell viability. This also includes code to process experimental data and validate model predictions.

Figures

All the figures published in the paper can be found in the folder figures and some specific figures generated as part of model building code can be found in figures/ALMANAC_klaeger_johnson