PertInInt

PertInInt identifies genes involved in cancer by detecting enrichment of somatic mutations at protein interaction and other functional sites to elucidate mechanisms of oncogenesis.

Key Features:

• Integrative analysis framework: Integrates knowledge about protein interaction sites (DNA, RNA, peptides, ions, and small molecules), domain information, evolutionary conservation, and gene-level mutation data.
• Enrichment-based gene identification: Detects regions enriched for somatic mutations at interaction or other functional sites to nominate genes with functional roles in cancer.
• Discovery of known and novel cancer genes: Identifies both previously characterized and putative novel cancer-associated genes across tumor types.
• Large-scale application: Applied to a dataset of 10,037 tumor samples spanning 33 cancer types.
• Mechanistic insight into oncogenesis: Reveals frequent enrichment of somatic mutations in binding residues and domains of oncogenes and tumor suppressors, implicating perturbation of interaction potential as a common driver.

Scientific Applications:

• Gene discovery in cancer genomics: Prioritizes genes whose functional sites are disrupted by somatic mutations for further study.
• Mechanistic characterization: Supports investigation of how mutation enrichment at interaction sites affects oncogenes and tumor suppressors.
• Target prioritization: Aids selection of candidate genes and interaction sites for experimental validation and therapeutic development.

Methodology:

PertInInt systematically integrates protein interaction site annotations (DNA, RNA, peptides, ions, small molecules), domain annotations, evolutionary conservation, and gene-level mutation data, and performs enrichment analysis of somatic mutations at protein interaction and other functional sites.