PepQuery

PepQuery performs peptide-centric validation by matching MS/MS spectra to sample- or disease-specific DNA/RNA-derived peptide sequences to validate novel peptides arising from genomic alterations for proteogenomic analyses.

Key Features:

• Peptide-centric search: Targets only candidate peptides derived from novel DNA or protein sequences rather than evaluating all possible spectrum–peptide pairs.
• Direct use of sequencing-derived sequences: Utilizes sample- or disease-specific sequences obtained from DNA or RNA sequencing data, eliminating the need for constructing comprehensive custom protein databases for the search.
• Validation targets: Supports validation of novel proteins, splice junctions, and single amino acid variants.
• Unrestricted modification searching: Permits unrestricted modification searches to reduce false positives (reported up to ~95% reduction).
• Demonstrated performance: Shows high sensitivity and specificity in validation based on simulations and experimental MS/MS datasets.

Scientific Applications:

• Proteogenomic validation: Validates peptides and protein products that arise from genomic alterations identified by next-generation sequencing.
• Biomarker and target discovery: Supports identification and validation of candidate disease biomarkers and therapeutic targets at the peptide/protein level.
• Integration of omics data: Enables integration of genomics and proteomics evidence to confirm translation of novel sequences into detectable peptides.
• Precision medicine research: Facilitates sample-specific peptide validation relevant to personalized or disease-specific studies.

Methodology:

PepQuery performs a peptide-centric search by matching experimental MS/MS spectra to candidate peptides derived from DNA/RNA sequencing, allows unrestricted modification searching, and reports validation outcomes; performance has been evaluated using simulations and experimental datasets.