TF_Mutation_Stability

Objective:
This project investigates the stability effects of transcription factors (TFs) mutations, focusing on their impact on structural stability and gene expression profiles in Luminal A (LumA) cancer patients. Using a systems biology approach, the analysis integrates multi-omics data, combining structural insights, gene regulatory dynamics, mutational data, and gene expression to uncover mechanisms driving oncogenesis.

Tools Used:

1. MAVISp: A modular framework for the structural interpretation of mutations.
2. Moonlight2R: A predictive framework for identifying cancer driver genes.

By integrating these tools, the study identifies genes influenced by mutated TFs and elucidates their roles in cancer progression.

---

Directory Structure

1. ./rawdata

Contains input data used to generate the results (external to this project):

• mutations.csv: TCGA-BRCA mutation data.
• BRCA_BRCA.LumA_dataDEGs.rda: Differential gene expression data for TCGA-BRCA (LumA).
• BRCA_BRCA.LumA_dataFilt_HUGO.rda: Normal counts of gene expression.
• trrust_rawdata_human.tsv: List of transcription factors, their targets, and regulation modes from TRRUST.

2. ./results

Generated results from this project:

• FEA_lumA.rda, URA_lumA.rda, GRN_lumA.rda, PRA_lumA.rda, TF_lumA.
• Summaries:
  • TFinfluence_summary_table.csv
  • TFinfluence_TFmutations.csv
  • PRA_drivers.csv.

3. ./mavisp_csv

MAVISp database files.

4. ./scripts

R scripts used for analysis and generating results/figures:

• run_moonlight.R:

  • Runs the Moonlight2R pipeline.
  • Produces all results and figures:
    • plotFEA_lumA.png
    • plot_TFinfluence_MAVISp_coverage.png
    • plot_TFinfluence_total_coverage.png.

• somatic_mutation_analysis.R:

  • Runs the Somatic Mutational Analysis (as part of the thesis).
  • Produces:
    • maf_oncoplot.png
    • maf_summary.png
    • All lolliplots.

5. ./figures

Figures generated by the scripts.

---

How to Run

1. Place required raw data in the ./rawdata directory.
2. Execute the scripts in ./scripts:
   • run_moonlight.R
   • somatic_mutation_analysis.R.
3. View generated results in the ./results directory.
4. Check figures in the ./figures directory.

---