CrypticProteinDB

CrypticProteinDB catalogs non-canonical proteins from proteome and immunopeptidome datasets to enable proteogenomic characterization of non-canonical open reading frames (ncORFs) in cancer.

Key Features:

• Extensive Dataset Integration: Integrates data from over 900 patient proteomes and 26 immunopeptidome datasets across 14 cancer types.
• Non-Canonical ORFs Analysis: Identifies a nonredundant set of 9,760 upstream, downstream, and out-of-frame ncORFs within protein-coding genes and 12,811 ncORFs associated with noncoding RNAs.
• Differential Expression Insights: Annotates 6,486 ncORFs derived from differentially expressed genes and reports 340 ncORFs translated across eight or more cancers.
• Immunotherapy Targets: Reports 34 epitopes and 8 neoantigens from non-canonical proteins identified as cancer immunotargets in two cohorts.
• Comprehensive Validation Approach: Employs bottom-up proteogenomic analysis and targeted peptide validation to corroborate novel peptide identifications.

Scientific Applications:

• Biomarker and Therapeutic-Target Discovery: Integration of proteomic, immunopeptidomic, genomic, and transcriptomic data to identify and prioritize ncORF-derived biomarker and therapeutic candidates.
• Neoantigen and Vaccine Development: Identification of epitopes and neoantigens from non-canonical proteins to support neoantigen-based vaccine and immunotherapy research.
• Comparative Cancer Proteogenomics: Cross-cancer analysis across 14 cancer types to assess prevalence, ubiquity, and translation patterns of ncORFs.

Methodology:

Proteogenomic analysis combining whole-cell proteomes and immunopeptidomes, employing bottom-up proteogenomic analysis and targeted peptide validation.