Structure-PPi

Structure-PPi annotates cancer-related germline and somatic genetic variants on three-dimensional protein structures, emphasizing protein–protein interaction interfaces to assess variant functional and structural impact.

Key Features:

• Integration of Omics Data: Integrates NGS-derived omics data to analyze germline and somatic variants in the context of cancer.
• Utilization of Public Databases: Leverages annotations from Interactome3D, UniProtKB, InterPro, APPRIS, dbNSFP, and COSMIC to supply structural and variant-level information.
• Focus on Protein Interaction Interfaces: Annotates variants located at protein–protein interaction interfaces within three-dimensional structures.
• Functional Site Analysis: Reports variant occurrences in catalytic regions, ligand-binding domains, and posttranslational modification sites.
• Complementary Pathogenicity Insights: Provides contextual information that complements pathogenicity prediction methods and assists in distinguishing false-positive predictions.
• Mechanistic and Biological Insights: Offers mechanistic interpretations of how variants may impact protein function and interaction networks relevant to cancer.

Scientific Applications:

• Cancer variant interpretation: Mapping and interpreting structural implications of germline and somatic variants for cancer research.
• Variant prioritization and classification: Contextualizing pathogenicity predictions to refine variant classification and prioritize candidates for functional follow-up.

Methodology:

Structure-PPi extracts features and annotations from Interactome3D, UniProtKB, InterPro, APPRIS, dbNSFP, and COSMIC and maps NGS-derived variant data onto three-dimensional protein structures and annotated functional sites.