chip_seq_regulons

This repo contains code used in the preprint "Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs"

Installation

The installation of the dependencies required for the repository, requires conda. Further instructions on installing Anaconda could be found here

git clone https://github.com/LappalainenLab/chip_seq_regulons.git
cd chip_seq_regulons/
conda env create --file environment.yaml
conda activate chip_seq_reg

Sample data:

Sample data is available in the data directory, which is structured to align with the pipeline's requirements. Ensure that the file names and folder hierarchy are maintained as provided.

Annotation pipeline:

Contains scripts to run the S2Mb, S100Kb, S2Kb, M100Kb, and M2Kb TF-target gene annotation pipelines

1. Put all necessary data files, i.e. ReMap and RNA-Seq data, to respective data directories (see data directory structure below)
2. Run annotation pipeline with

bash pipeline/run_one_pipeline.sh sample_cell sample_RNA_1,sample_RNA_2 sample_DNAse sample_ATAC

where sample_cell is the name of the cell line; sample_RNA_1,sample_RNA_2 are comma-separated RNA-Seq replicate data accessions (i.e. file names); sample_DNAse is the DNAse-Seq data accession (i.e. file name); sample_ATAC is the ATAC-Seq data accession (i.e. file name).

Benchmarking:

To replicate manuscript results:

1. Collect regulons from the respective Zenodo repository.
2. Run benchmarking scripts with

# Compare regulons
python benchmark/benchmark_with_decoupler_{cell_line}_comparison.py

# Compare filtering strategies
python benchmark/benchmark_with_decoupler_{cell_line}_filtering.py

3. To extract regulons' statistics

Rscript benchmark/data_summary_stats.R

4. To perform enrichment analysis of TF-target gene pairs in PPI interactions

Rscript benchmark/test_ppi_enrich.R

5. To perform enrichment analysis of TF-target gene pairs in biological networks for the K562 cell line (see Methods section of the manuscript for deatils)

Rscript benchmark/test_net_enrich.R

6. To perform enrichment analysis of TF-target gene pairs in coexpression networks for the K562 cell line

Rscript benchmark/test_coexp_enrich.R

Case studies:

Notebooks used to conduct cancer case studies are located at case_studies

Figures:

Scripts to reproduce figures from the manuscripts can be run by

Rscript figures/manuscript/{script_name}.R

Citation

Minaeva, M., Domingo, J., Rentzsch, P., & Lappalainen, T. (2024). Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs. bioRxiv, 2023-12. https://doi.org/10.1101/2023.12.31.573765