SCOPE: Revealing Hidden Mechanisms in Phenotypic Screens Through Target and Pathway Enrichment.

ABSTRACT: Phenotypic screening enables discovery of small molecules without requiring predefined targets, but mechanistic interpretation remains challenging due to polypharmacology and pathway complexity. We developed SCOPE (Screening Compound Ontology for Pathway Enrichment), a KNIME-based computational framework that resolves the molecular drivers of phenotypic activity by linking compound-level screening data to annotated targets and pathways. SCOPE integrates multi-source target annotations and performs statistical enrichment to identify shared mechanisms of action. Applied to a high-throughput screen for modulators of ER-stress induced secretion of endoplasmic reticulum (ER) resident proteins, a process known as exodosis, SCOPE identified calcium signaling as the most enriched KEGG pathway with

SUBMITTER: Kapoor A 

PROVIDER: S-EPMC12338551 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature