MasterPATH

MasterPATH identifies molecular pathway members from functional genomics screening data by integrating directed and undirected interactomes and applying shortest path algorithms and centrality measures to subnetworks induced by hit genes and final implementers.

Key Features:

• Shortest path and centrality analysis: Applies shortest path algorithms and node/path centrality measures to detect key elements in molecular pathways.
• Interactome integration: Integrates directed and undirected networks from HIPPIE, SIGNOR, SignaLink, TFactS, KEGG, TransmiR, and miRTarBase.
• Subnetwork induction: Constructs subnetworks induced by hit gene lists and specified final implementers (genes directly responsible for phenotypic outcomes).
• High-throughput data support: Analyzes hit lists derived from loss-of-function screens and transcriptome profiling.
• Node and path prioritization: Flags nodes and short paths with significant centrality within induced subnetworks to prioritize pathway members.
• miRNA–target integration: Incorporates miRNA regulatory interactions via TransmiR and miRTarBase to connect regulatory miRNAs with target genes.

Scientific Applications:

• Muscle differentiation analysis: Analysis of miRNA loss-of-function screens and transcriptome profiling during terminal human muscle differentiation.
• miRNA regulatory discovery: Identification of regulatory miRNAs such as miR-1, miR-125b, and miR-216a and their targets involved in myogenesis.
• Regulator-target linking: Linking major skeletal myogenesis regulators MYOD and SMAD3 to both previously known and novel muscle-related targets.
• Oxidative DNA damage recognition: Exploration of genes regulating oxidative DNA damage recognition and elucidation of the interaction between H3 and SETDB1 proteins.

Methodology:

Integrates directed and undirected interactomes from HIPPIE, SIGNOR, SignaLink, TFactS, KEGG, TransmiR and miRTarBase, induces subnetworks from hit genes and final implementers, and applies shortest path algorithms and centrality measures to identify nodes and short paths with significant centrality.