StrongestPath

StrongestPath identifies cascades of protein–protein interactions and signaling pathways within Cytoscape 3 to reveal high-confidence interaction paths connecting proteins and regulatory relationships such as transcription factor–target gene activation or inhibition.

Key Features:

• Cascade Identification: Discovers one or more interaction cascades linking specified proteins across PPI and signaling networks.
• Confidence Scoring: Processes interactions annotated with confidence scores to identify cascades with the highest total confidence.
• Network Extraction and Expansion: Extracts subnetworks for a predefined protein set from selected databases and expands them by adding proteins with the highest number of high-confidence interactions.
• Regulatory Path Analysis: Identifies regulatory paths, including activation or inhibition, between sets of transcription factors and their target genes.
• Database Flexibility: Supports built-in human and mouse PPI/signaling network databases and user-provided databases for other organisms.

Scientific Applications:

• Pathway Protein Prioritization: Identifies key proteins centrally positioned within signaling pathways, demonstrated by analysis of 12 NetPath signaling pathways to pinpoint critical pathway proteins via strongest interaction paths.
• Regulatory Mechanism Analysis: Maps activation and inhibition paths between transcription factors and target genes to elucidate gene regulatory mechanisms.

Methodology:

Processes interaction confidence scores to compute total-confidence cascades, extracts subnetworks from selected databases, expands networks by adding proteins with the highest number of high-confidence interactions, and identifies activation/inhibition regulatory paths between transcription factors and target genes within Cytoscape 3 using built-in human and mouse databases or user-provided databases.