dpGSEA

dpGSEA performs gene set enrichment analysis that incorporates the biological directionality of drug-derived gene sets to identify phenotypically relevant drug targets from transcriptomic data.

Key Features:

• Biological Directionality: Incorporates the directionality of gene modulation to interpret drug-induced upregulation and downregulation.
• Drug-Defined Gene Sets: Focuses enrichment on drug-defined gene sets to identify specific perturbations caused by chemical compounds.
• Modified GSEA Integration: Implements a modified Gene Set Enrichment Analysis (GSEA) approach that integrates directionality of drug-induced expression changes.
• Transcriptomic Enrichment: Operates on transcriptomic data to prioritize phenotype-relevant targets based on expression signatures.
• Cross-Dataset Detection: Detects drug perturbations across independent public datasets.

Scientific Applications:

• Validation of drug effects: Confirmed effects of fluvastatin, paclitaxel, and rosiglitazone on gastroenteropancreatic neuroendocrine tumor cells.
• Drug target discovery in HIV: Identified phenotypically relevant targets within differentially expressed genes from CD4+ T regulatory cells in HIV-infected individuals undergoing antiviral therapy, including genes associated with virion replication, cell cycle dysfunction, and mitochondrial dysfunction.
• Screening for perturbations: Useful for screening potential drug-targeting molecules by detecting specific gene perturbations linked to compound treatment.

Methodology:

Uses a modified Gene Set Enrichment Analysis (GSEA) that integrates the directionality of drug-induced gene expression changes and distinguishes upregulated from downregulated genes in response to treatments.