GliomaGEM: Glioma metabolic modelling for repurposing of single and combination drugs.

Reference: Ali Kishk, Maria Pires Pacheco, Tony Heurtaux, Thomas Sauter, Metabolic models predict fotemustine and the combination of eflornithine/rifamycin and adapalene/cannabidiol for the treatment of gliomas, Briefings in Bioinformatics, Volume 25, Issue 3, May 2024, bbae199, https://doi.org/10.1093/bib/bbae199

• Data: expression data for TCGA-GBM and TCGA-LGG from three sources

• CRISPR: DepMap 22Q1 CRISPR screen

• Primary_target_databases: Three drug-target databases (DrugBank, PROMISCUOUS, Drug Repurposing Hub)

• Primary_target_databases/Orphandrug_GlialTumor.csv : Investigational anti-glioma drugs downloaded for OrhanDrug

• Primary_target_databases/Approved_anti_brain_cancers.csv

• Supplementary File 2.xlsx: Literature data for gene KO, drug response and clinical trials

• Sample_models/Subtypes_Models_w_Transcripts: Built sample models for the three glioma subtypes

• Concensus_models : Concensus models for the three glioma subtypes and the control model

Analysis steps

Data preprocessing

Download the complete metadata for TCGA-GBM and TCGA-LGG

TCGA_Biolinks_Download.R

PCA of the expression data for the three subtypes

Preprocess_TCGA.R

Model Building

Generate a consistent Human 1 model

Get_Consistent_Human1.m

Sample model building over 3 reconstructions, medium/ no medium, and 3 datasets

Model_Building_SampleLevel_Three_Models_CSF.m

Clustering reaction presence for choosing optimal combination of: data, medium and reconstruction

TCGA_Data_Model_Selection.R

Concensus model building

Model_Building_Subtype_Three_Models_CSF.m

Copy best model in sample clustering to Concensus_models

mkdir Concensus_models cp Sample_models/Subtypes_Models_w_Transcripts/Recon3D_Rahman2015__CSF_Thiele2020/* Concensus_models/ Models_Statistics_Consensus.m

Single gene deletion and FVA as model quality contro

Model_Gene_Deletion_and_FVA.m

Prepare depmap CRISPR data to compare approved vs predicted drug targets

Classify_Glioma_Celllines.R CRISPR_DepMap_Data_Splitting.m

Drug Deletion

Parse DrugBank V5 from .xml to csv

DrugBank-Parsing.ipynb

Merge drug-target databases prior the drug deletion

Merge_target_databases.R

Drug deletion of the three glioma models

Drug_Deletion_Glioma.m

Toxicity analysi of predicted drugs in the control model

Drug_Deletion_Control.m

Merce drug responses form HTS for IC50, viability reduction, andt xenograft data

Merge_Drug_Response_Databases_IC50.R Merge_Drug_Response_Databases_with_Viability.R Merge_Drug_Response_Databases_Xenografts.R

Create all main and suppl. figures of the paper

Visualizing_the_results.R