PharmGWAS

PharmGWAS integrates genome-wide association study (GWAS) data with molecular compound perturbation signatures to identify genetically-informed disease–drug associations by comparing genetically-regulated expression signatures with drug-induced signatures for drug repurposing.

Key Features:

• GWAS coverage: Incorporates 1,929 GWAS datasets covering a wide array of diseases.
• Perturbation signatures: Includes 724,485 perturbation signatures related to 33,609 molecular compounds.
• Signature comparison: Performs reverse relationship analysis between genetically-regulated expression signatures and drug-induced signatures.
• Connectivity methods: Employs six distinct connectivity methods to evaluate disease–drug relationships.
• Association catalog: Produces a catalog of 740,227 genetically-informed disease–drug associations derived from drug-perturbation signatures.

Scientific Applications:

• Drug repurposing and discovery: Prioritizes existing small molecules for new therapeutic indications based on genetic evidence.
• Combination therapy exploration: Enables identification of compound pairs or combinations suggested by complementary perturbation signatures and genetic signals.
• Adverse effect and resistance inference: Supports identification of potential drug resistance mechanisms or side-effect associations inferred from genetic and perturbation signature concordance.

Methodology:

Integration of 1,929 GWAS datasets with 724,485 molecular compound perturbation signatures and reverse relationship analysis between genetically-regulated expression signatures and drug-induced signatures using six distinct connectivity methods.