Structure-PPi: A module for the annotation of cancer-related single-nucleotide variants at protein-protein interfaces

Abstract

Motivation: The interpretation of cancer-related single-nucleotide variants (SNVs) considering the protein features they affect, such as known functional sites, protein-protein interfaces, or relation with already annotated mutations, might complement the annotation of genetic variants in the analysis of NGS data. Current tools that annotate mutations fall short on several aspects, including the ability to use protein structure information or the interpretation of mutations in protein complexes. Results: We present the Structure-PPi system for the comprehensive analysis of coding SNVs based on 3D protein structures of protein complexes. The 3D repository used, Interactome3D, includes experimental and modeled structures for proteins and protein-protein complexes. Structure-PPi annotates SNVs with features extracted from UniProt, InterPro, APPRIS, dbNSFP and COSMIC databases. We illustrate the usefulness of Structure-PPi with the interpretation of 1 027 122 non-synonymous SNVs from COSMIC and the 1000G Project that provides a collection of 172 700 SNVs mapped onto the protein 3D structure of 8726 human proteins (43.2% of the 20 214 SwissProt-curated proteins in UniProtKB release 2014-06) and protein-protein interfaces with potential functional implications.