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

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

This repository contains raw and processed files utilized in Minaeva et. al 2023. Code used to generate these files is available at https://github.com/LappalainenLab/chip_seq_regulons Descriptions of 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 (K562, HepG2, MCF7, or GM12878). `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 (K562, HepG2, MCF7, or GM12878). 1-functional_annotation `{cell_line}_regulon_with_motifs.tsv`: Cell-line specific regulons constructed by the respective approach (S2Mb, M2Kb, or S2Kb) with motif annotation generated using HOMER (see Methods for details). 1-network_enrichment `enrich_scores_remap_all_tfs_K562.tsv`: Results of fitting logistic regression for testing enrichment of 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, TRRUST regulons using the decoupler package and 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 KnockTF database. Cell lines considered are K562, HepG2, and MCF7 (see Methods for benchmarking pipeline details). 3-tf_activity `aml_k562_activity_{regulon}.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.tsv`: Summary of the TF activity analysis for statistically significantly dysregulated TFs between healthy hematopoietic stem cells (HSCs) and abnormal AML progenitor cells across regulons. `aml_dhsc_ahsc_activity_{regulon}.tsv`: Results of TF activity analysis based on a respective regulon between leukemic activated and dormant HSCs following the decoupler pipeline. Regulons considered are GM12878-specific and K562-specific ChIP-Atlas and M2Kb regulons and generalized CollecTri regulon. `aml_activity_estimates_dhsc_ahsc.tsv`: Summary of the TF activity analysis for statistically significantly dysregulated TFs between leukemic activated and dormant HSCs across regulons. `aml_gm12878_activity_{regulon}.tsv`: Results of TF activity analysis based on a respective regulon between healthy HSCs and abnormal AML progenitor cells following the decoupler pipeline. Regulons considered are GM12878-specific ChIP-Atlas and M2Kb regulons and generalized CollecTri regulon. `aml_gm12878_activity_estimates_hsc.tsv`: Summary of the TF activity analysis for statistically significantly dysregulated TFs between healthy HSCs and abnormal AML progenitor cells 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.tsv`: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between healthy HSCs and abnormal AML progenitor cells the following decoupler pipeline. Databases considered are COSMIC, DisGeNet, OMIM and KEGG, and regulons considered are GM12878-specific and K562-specific ChIP-Atlas and M2Kb regulons and generalized CollecTri regulon. `aml_{database}_enrich_{regulon}_dhsc_ahsc.tsv`: Results of enrichment analysis of dysregulated TFs identified based on a respective regulon between leukemic activated and dormant HSCs the following decoupler pipeline. Databases considered areere considered databases are COSMIC, DisGeNet, OMIM and KEGG, and regulons considered are GM12878-specific and 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 basalbreast cancer following the decoupler pipeline. Databases considered are COSMIC, DisGeNet and OMIM , and 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 the following decoupler pipeline. Databases considered are COSMIC, DisGeNet and OMIM, and 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, and regulons considered are HepG2-specific ChIP-Atlas and M2Kb regulons and generalized CollecTri regulon. regulons Here cell_lines are: K562, HepG2, MCF7 and GM12878 `ChIP-Atlas_target_genes_{cell_line}.tsv`: Customized ChIP-Atlas regulons (see Methods for details) `{cell_line}_all_regulons.tsv`: S2Mb, M2Kb, and S2Kb regulons generated in this study with covariates used in network enrichment analysis (see Methods for details). `{cell_line}_regulon.tsv`: S2Mb, M2Kb, and S2Kb regulons generated in this study with filters used for benchmarking (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 regulon in PPI networks (see Methods and corresponding GitHub repo for details). Cell lines considered are K562, HepG2, MCF7, and GM12878.