Abstract

Data Integration: Amino Acids to Genomic Coordinates

Author(s): Priyanshu Sharma

Our understanding of genotype-phenotype connections will increase with the combination of proteomic, transcriptomic, and genetic variant annotation data. Such multi-omic investigations have not expanded to chemoproteomics, a method that evaluates the inherent reactivity and possible "druggability" of nucleophilic amino acid side chains, in part due to challenges involved with appropriate inter-database mapping. We tested mapping methods to connect cysteine and lysine residues identified by chemoproteomics with their genomic locations. Database updates cycles and dependence on stable identifiers, according to our findings, can result in widespread misidentification of tagged residues. We combined our chemoproteomics data with computational methods for predicting genetic variant pathogenicity, which revealed that codons of highly reactive cysteines are enriched for genetic variants predicted to be more deleterious and allowed us to identify and functionally characterize a new damaging residue in the cysteine protease caspase-8.