Chemoproteogenomics

Chemoproteogenomics integrates chemoproteomic, whole exome, and RNA-seq data to reveal the landscape of cysteine genetic variation and guide proteoform-specific biology and therapeutic discovery.

Key Features:

• Multi-omics Data Integration: The platform integrates chemoproteomic, whole exome, and RNA-seq data for comprehensive analysis of cysteine genetic variation.
• Customized Two-Stage FDR Controlled Proteomic Search: A specialized false discovery rate controlled search strategy enhances identification confidence for variant cysteines.
• Sample-Matched Combinatorial Variant Databases: The platform generates combinatorial variant databases matched to individual samples for personalized proteogenomic analysis.
• Redox Proteomics Compatibility: The platform is compatible with redox proteomics methods for analyzing functional and redox-sensitive cysteine residues.
• Small Molecule Screening Compatibility: The platform supports integration with small molecule screening for therapeutic discovery applications.

Scientific Applications:

• Cysteine Acquisition Detection: Analysis reveals cysteine acquisition as a ubiquitous feature of both healthy and cancer genomes, with elevation in contexts of decreased DNA repair.
• Missense Variant Cysteinome Stratification: The platform stratifies the missense variant cysteinome to identify acquired cysteines as potential driver mutations and precision therapy targets.
• Variant-Specific Chemical Probe Development: Identification of reference cysteines proximal to missense variants enables targeted chemical probe development campaigns.
• Druggability Assessment: Identification of acquired cysteines enables functional analysis of potential druggability and susceptibility to oxidation.

Methodology:

The platform employs a customized two-stage false discovery rate (FDR) error controlled proteomic search that integrates chemoproteomic, whole exome, and RNA-seq data.