CGIdb

CGIdb identifies genetic interactions that influence drug resistance and sensitivity in cancer by integrating TCGA copy number alteration profiles, whole-exome mutation data, and functional screen results to support biomarker discovery.

Key Features:

• Data Integration: Integrates TCGA copy number alteration profiles, whole-exome mutation data, and functional screen results for comprehensive analysis across cancer types.
• Detection of Genetic Interactions: Identifies and catalogs synthetic viability (SV) interactions associated with drug resistance (4,529 SV interactions) and synthetic lethality (SL) interactions associated with increased drug sensitivity (10,637 SL interactions).
• Pharmacogenomic Analysis: Analyzes pharmacogenomic datasets to link specific genetic alterations to drug responses, exemplified by deletions in HDAC1 and DVL1 showing SV effects that confer resistance to HDAC1 inhibitors and implicating the Notch signaling pathway.
• Clinical Correlation: Correlates genetic interactions and gene expression patterns, such as low HDAC1 and DVL1 expression, with clinical outcomes and prognosis.
• Curation of Reported Interactions: Aggregates reported genetic interactions from multiple studies into a centralized repository for integrated analysis.

Scientific Applications:

• Biomarker Identification: Enables discovery of genetic biomarkers that predict drug resistance or sensitivity in cancer.
• Pharmacogenomics: Supports analysis of how specific genetic alterations modulate patient responses to therapies using pharmacogenomic datasets.
• Patient Stratification: Facilitates stratification of patients for therapeutic interventions based on genetic interaction profiles.
• Therapeutic Target Prioritization: Informs prioritization of synthetic lethality targets to enhance treatment responses.

Methodology:

Integrates TCGA copy number alteration profiles, whole-exome mutation data, and functional screen results; analyzes pharmacogenomic datasets; detects synthetic viability (SV) and synthetic lethality (SL) interactions (reporting 4,529 SV and 10,637 SL interactions); correlates interactions with clinical outcomes; aggregates reported interactions from published studies.