PathExpand

PathExpand extends predefined protein sets by mapping them onto a comprehensive protein-protein interaction network to incorporate densely interconnected interaction partners and enable analysis of pathway enrichment in genes mutated in cancers such as pancreatic cancer.

Key Features:

• Integration of Pathway Databases and Interaction Networks: Maps pathway database protein sets onto interaction networks derived from functional genomic experiments to broaden pathway representations.
• Network Topology and Molecular Function Annotations: Identifies proteins with distinctive network topological features and molecular function annotations as candidate pathway components or regulators.
• Identification of Cancer-Related Pathways: Extends pathways with additional interaction partners to assess enrichment among genes mutated in cancers, including pancreatic cancer.
• Functional Analysis of Non-Annotated Mutated Genes: Links previously non-annotated cancer-mutated genes to expanded pathways through integration of canonical pathway knowledge and large-scale interaction data.

Scientific Applications:

• Cancer pathway analysis: Analyze deregulation of cellular pathways by assessing enrichment of cancer-mutated genes within expanded pathway models.
• Annotation of mutated genes: Assign functional context to non-annotated mutated genes by connecting them to expanded canonical pathways via interaction data.
• Identification of pathway components and regulators: Discover candidate novel components or regulators based on network topology and molecular function annotations.
• Biomarker and target hypothesis generation: Prioritize potential therapeutic targets or biomarkers by identifying mutated genes associated with expanded pathway modules.

Methodology:

Map predefined protein sets onto an extensive protein-protein interaction network, identify and include densely interconnected interaction partners, detect proteins with distinctive network topological features and molecular function annotations, extend the pathway sets with these proteins, and analyze enrichment of the expanded pathways in genes mutated in cancers such as pancreatic cancer.