PATH-SURVEYOR

PATH-SURVEYOR performs pathway-level survival analysis to identify associations between molecular pathways, immune signatures, and clinical outcomes for applications in immuno-oncology and drug repurposing.

Key Features:

• Pathway-level survival analysis: Performs survival analysis at the pathway resolution to evaluate associations between pathway activity, immune signatures, and patient outcomes.
• Cox proportional-hazard model: Supports Cox proportional-hazard modeling to assess the impact of pathways and covariates on survival.
• Hazard Ratio-ranked GSEA: Ranks genes by hazard ratio and applies gene set enrichment analysis to identify gene sets associated with survival.
• Pathway clustering: Groups pathways by similarity and shared associations with clinical endpoints to reveal pathway-level patterns.
• Immune biomarker identification in ICI-treated melanoma: Identifies immune populations and biomarkers predictive of checkpoint inhibition (ICI) efficacy in melanoma cohorts.
• Inverse drug-target association analysis: Performs inverse association analyses between drug targets and clinical endpoints to nominate candidate repurposing targets in high-risk KMT2A-fusion-positive pediatric AML.
• Validation with Genomics of Drug Sensitivity database: Validates nominated drug targets using AML cell line data from the Genomics of Drug Sensitivity database.

Scientific Applications:

• Immuno-oncology biomarker discovery: Detects immune populations and pathway biomarkers associated with response to checkpoint inhibitors in melanoma.
• Drug repurposing in pediatric AML: Identifies and prioritizes drug targets for high-risk KMT2A-fusion-positive pediatric acute myeloid leukemia using inverse association analysis.
• Pathway-informed survival and prognostic analyses: Enables pathway-based assessment of molecular and immune factors that influence patient survival and prognostic modeling.

Methodology:

Uses Cox proportional-hazard modeling, Hazard Ratio-ranked GSEA, pathway clustering, inverse association analysis between drug targets and clinical endpoints, and validation against AML cell lines from the Genomics of Drug Sensitivity database.