Specifying cellular context of transcription factor regulons for exploring context-specific gene regulation programs

This repository contains the raw and processed files used in Minaeva et al. 2024.

In this version, we have revised the regulon construction pipeline and expanded the dataset to cover 40 common cell lines.

The code used to generate these files is available at GitHub - LappalainenLab/chip_seq_regulons.

The descriptions of the files contained within each subdirectory are as follows:

1-dataset_stats

• per_gene_stats_{approach}_{cell_line}.tsv: Number of TFs regulating a gene according to the respective approach (S2Mb, M2Kb, or S2Kb) in a given cell line.
• per_tf_stats_{approach}_{cell_line}.tsv: Number of target genes regulated by a TF according to the respective approach (S2Mb, M2Kb, or S2Kb) in a given cell line.

1-network_enrichment

• enrich_scores_remap_all_tfs_K562.tsv: Results of fitting logistic regression for testing the enrichment of the K562 regulon in other biological networks (PPI, coexpression, experimental trans-networks).

2-plot_decoupler_comparison_benchmark_across_cells

• {cell_line}_comparison_benchmark.tsv: Results of benchmarking S2Mb, M2Kb, CollecTri, Dorothea, ChIP-Atlas, RegNet, and TRRUST regulons using the decoupler package and the KnockTF database. Cell lines considered are K562, HepG2, and MCF7 (see Methods for benchmarking pipeline details).

2-plot_decoupler_filter_benchmark_across_methods

• {cell_line}_filtering_benchmark.tsv: Results of benchmarking S2Mb, M2Kb, and S2Kb regulons with different filters applied using the decoupler package and the KnockTF database. Cell lines considered are K562, HepG2, and MCF7 (see Methods for benchmarking pipeline details).

3-tf_activity

• aml_k562_activity_{regulon}_sc.tsv: Results of TF activity analysis based on a respective regulon between healthy hematopoietic stem cells (HSCs) and abnormal AML progenitor cells following the decoupler pipeline. Regulons considered are K562-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• aml_activity_estimates_hsc_sc.tsv: Summary of the TF activity analysis for statistically significantly dysregulated TFs between healthy HSCs and abnormal AML progenitor cells across regulons.
• aml_dhsc_ahsc_activity_{regulon}_sc.tsv: Results of TF activity analysis based on a respective regulon between leukemic activated and dormant HSCs following the decoupler pipeline. Regulons considered are K562-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• aml_activity_estimates_dhsc_ahsc_sc.tsv: Summary of the TF activity analysis for statistically significantly dysregulated TFs between leukemic activated and dormant HSCs across regulons.
• bc_bas_activity_{regulon}.tsv: Results of TF activity analysis based on a respective regulon between healthy epithelial breast cells and malignant epithelial cells from basal breast cancer following the decoupler pipeline. Regulons considered are MCF7-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• bc_activity_estimates_bas.tsv: Summary of the TF activity analysis for statistically significantly dysregulated TFs between healthy epithelial breast cells and malignant epithelial cells from basal breast cancer across regulons.
• bc_lum_activity_{regulon}.tsv: Results of TF activity analysis based on a respective regulon between healthy epithelial breast cells and malignant epithelial cells from luminal type A breast cancer following the decoupler pipeline. Regulons considered are MCF7-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• bc_activity_estimates_lum.tsv: Summary of the TF activity analysis for statistically significantly dysregulated TFs between healthy epithelial breast cells and malignant epithelial cells from luminal type A breast cancer across regulons.
• hep_activity_{regulon}.tsv: Results of TF activity analysis based on a respective regulon between neoplastic and healthy liver cells following the decoupler pipeline. Regulons considered are HepG2-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• hep_activity_estimates.tsv: Summary of the TF activity analysis for statistically significantly dysregulated TFs between neoplastic and healthy liver cells across regulons.

3-tf_disease_enrichment

• aml_{database}_enrich_{regulon}_hsc_sc.tsv: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between healthy HSCs and abnormal AML progenitor cells following the decoupler pipeline. Databases considered are COSMIC, DisGeNet, OMIM, and KEGG. Regulons considered are K562-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• aml_{database}_enrich_{regulon}_dhsc_ahsc_sc.tsv: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between leukemic activated and dormant HSCs following the decoupler pipeline. Databases considered are COSMIC, DisGeNet, OMIM, and KEGG. Regulons considered are K562-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• bc_{database}_enrich_{regulon}_bas.tsv: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between healthy epithelial breast cells and malignant epithelial cells from basal breast cancer following the decoupler pipeline. Databases considered are COSMIC, DisGeNet, and OMIM. Regulons considered are MCF7-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• bc_{database}_enrich_{regulon}_lum.tsv: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between healthy epithelial breast cells and malignant epithelial cells from luminal type A breast cancer following the decoupler pipeline. Databases considered are COSMIC, DisGeNet, and OMIM. Regulons considered are MCF7-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.
• hep_{database}_enrich_{regulon}.tsv: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between neoplastic and healthy liver cells following the decoupler pipeline. Databases considered are COSMIC, DisGeNet, OMIM, and KEGG. Regulons considered are HepG2-specific ChIP-Atlas and M2Kb regulons, and generalized CollecTri regulon.

regulons

• {cell_line}_regulon.tsv: S2Mb, M2Kb, and S2Kb regulons generated in this study with all acquired annotations (see Methods for details).

External regulons used for comparison. Cell lines considered are K562, HepG2, MCF7, and GM12878:

• ChIP-Atlas_target_genes_{cell_line}.tsv: Customized ChIP-Atlas regulons (see Methods for details).
• Revised_Supplemental_Table_S3_Normal.csv: Dorothea regulon collected from supplementary materials of Garcia-Alonso et al. (2019).

s3-network_enrichment

• enrich_scores_remap_all_tfs_{cell_line}.tsv: Results of fitting logistic regression for testing the enrichment of cell-line-specific regulons in PPI networks (see Methods and corresponding GitHub repository for details). Cell lines considered are K562, HepG2, MCF7, and GM12878.