PON-P2

PON-P2 predicts the pathogenicity of amino acid substitutions (AASs) in cancer genomes to prioritize substitutions that affect proteins and pathways for cancer genomics analyses.

Key Features:

• Pathogenicity prediction: Predicts the pathogenicity of amino acid substitutions (AASs) within cancer genomes.
• Extensive analysis: Analyzes AASs derived from 6,861 cancer samples including whole genome and exome sequences across 30 distinct cancer types.
• Pathway enrichment analysis: Identifies biological pathways significantly affected by harmful AASs in proteins.
• Protein interaction network mapping: Maps proteins harboring harmful AASs onto protein interaction networks and assesses their central positions.
• Cross-cancer overlap analysis: Evaluates overlap of affected pathways across different cancer types to reveal common disrupted processes.
• Filtering of benign variations: Filters out putative benign AASs to refine the set of candidate pathogenic substitutions.

Scientific Applications:

• Cancer genomics research: Prioritizes substitutions and pathways for studies of cancer biology and mutational impact.
• Target identification for therapies: Highlights commonly affected pathways across cancers that may inform therapeutic targeting.
• Experimental follow-up: Refines variant lists and pathway candidates to guide experimental validation of functional effects.

Methodology:

Computational analysis of AASs from 6,861 cancer samples (whole genome and exome sequencing across 30 cancer types), pathway enrichment analyses of proteins with harmful AASs, mapping to protein interaction networks to assess centrality, cross-cancer pathway overlap analysis, and filtering of putative benign AASs.