Structure-PPi

Structure-PPi annotates cancer-related single-nucleotide variants (SNVs) by mapping them onto three-dimensional protein structures to assess their impact at protein–protein interfaces.

Key Features:

• 3D Structural Analysis: Uses the Interactome3D repository of experimental and modeled 3D structures of proteins and protein–protein complexes to analyze SNVs in spatial context.
• Database Integration: Integrates annotations and features from UniProt, InterPro, APPRIS, dbNSFP, and COSMIC to enrich variant annotation.
• Interface-focused Annotation: Identifies and characterizes SNVs located at protein–protein interfaces to evaluate potential effects on interactions.
• Variant Mapping Coverage: Maps approximately 172,700 non-synonymous SNVs onto the 3D structures of 8,726 human proteins, covering 43.2% of SwissProt-curated proteins.
• Contextual Functional Analysis: Analyzes variants in relation to known functional sites and previously annotated mutations to infer potential functional consequences.
• Feature Aggregation per Variant: Aggregates a comprehensive set of features extracted from integrated databases for each annotated variant.

Scientific Applications:

• Cancer genomics interpretation: Provides structural context to aid interpretation of non-synonymous SNVs implicated in cancer and their potential effects on protein function and interactions.
• Large-scale variant annotation: Supports mapping and interpretation of variants from large datasets such as COSMIC and the 1000G Project to inform studies of somatic and germline variation.

Methodology:

Maps non-synonymous SNVs onto Interactome3D experimental and modeled 3D structures, analyzes variants relative to known functional sites, protein–protein interfaces and previously annotated mutations, and annotates each variant using aggregated features from UniProt, InterPro, APPRIS, dbNSFP and COSMIC.