Code for processing and analysing the combinatorial screen data presented in the manuscript "High-throughput profiling of drug interactions in Gram-positive bacteria” (https://www.biorxiv.org/content/10.1101/2022.12.23.521747v1).
All drug-drug interactions (with their effect size and adjusted p-value) detected with this pipeline are listed in Supplementary Table 2 (antibiotic screen conducted in S. aureus Newman and DSM 20231, B. subtilis 168 and S. pneumoniae D39V) and Supplementary Table 6 (non-antibiotic drug screen in S. aureus DSM 20231). https://www.biorxiv.org/content/10.1101/2022.12.23.521747v1.supplementary-material
The repository tree has the following structure:
data: unprocessed optical density measurementsdataprepfolder: R scripts for pre-processing of the raw screen dataqualitycheckdirectory: scripts for quality controlanalysis: high-level analysis of the screen data, computation of interaction scores, p-values and network analysisphylogeny: code and data for the phylogeny analysis presented in Fig. 1egrowthrates: growth rates from fitting a Baranyi model (Methods)
Note that here we use the following codes for the 4 Gram-positive bacterial strains:
| Code | Strain |
|---|---|
| K | S. aureus Newman |
| M | S. aureus DSM 20231 |
| D | B. subtilis 168 |
| P | S. pneumoniae D39V |
The main branch contains the data analysis pipeline for the drug combinatorial screen in Gram-positive bacterial species. In order to run the pipeline in the SLURM cluster environment:
sbatch pipeline.sh datadir batchnumber strain
For example, provided that the data is in and you wannt to process the data from batch 2 (strain K), submit the job as follows:
sbatch pipeline.sh data/screen_K 2 K
Furthermore, the data can be analyzed at the strain level, so that the significant interactions are identified separately for each strain. First run permutation test in parallel:
sbatch permtest.sh datadir strain
For example if one wants to process all of the data for strain K:
sbatch permtest.sh data/screen_K K
Next run plot.sh script to generate visualizations of individual drug combinations:
sbatch plot.sh datadir strain
# strain K
sbatch plot.sh data/screen_K K