PharmacoDB

PharmacoDB integrates cancer pharmacogenomic datasets to enable comparative analysis of drug dose-response and associations between genomic features and drug sensitivity across cell lines and compounds.

Key Features:

• Integration of Diverse Datasets: Consolidates data from NCI-60, PRISM (Profiling Relative Inhibition Simultaneously in Mixtures), Genomics of Drug Sensitivity in Cancer (GDSC), and the Genentech Cell Line Screening Initiative (gCSI), covering approved and investigational drugs across multiple tissue types.
• FAIR Data Pipelines: Implements FAIR principles using ORCESTRA and PharmacoDI pipelines to standardize data and support interoperability.
• Advanced Drug-Response Analyses: Enables computation of dose-response metrics, analysis of tissue distribution of dose-response metrics, and biomarker analysis.
• Curated Identifiers for Robust Comparisons: Curates cell line and chemical compound identifiers to maximize dataset overlap and enable extraction of consistent drug-response phenotypes despite technical and biological variation.
• Connectivity and Standardization with External Databases: Links and standardizes identifiers to other drug and cell line databases to improve cross-dataset comparisons.

Scientific Applications:

• Biomarker discovery: Correlates drug sensitivity measures with genomic features to identify potential biomarkers and therapeutic targets.
• Cross-study pharmacogenomic comparison: Performs comparative analyses of drug-response phenotypes across NCI-60, PRISM, GDSC, and gCSI datasets.
• Tissue-specific pharmacology: Assesses tissue distribution of dose-response metrics to study tissue-specific drug sensitivity.
• Predictor development: Supports development and validation of predictors of drug response from integrated pharmacogenomic data.

Methodology:

Consolidation of NCI-60, PRISM, GDSC, and gCSI datasets; curation of cell line and compound identifiers; implementation of ORCESTRA and PharmacoDI FAIR pipelines; computation of dose-response metrics and biomarker analyses.