CysDB: a human cysteine database based on experimental quantitative chemoproteomics

Cysteine chemoproteomics provides proteome-wide portraits of the ligandability or potential “druggability” for thousands of cysteine residues. Consequently, these studies are facilitating resources for closing the druggability gap, namely, achieving pharmacological manipulation of ∼96% of the human proteome that remains untargeted by U.S. Food and Drug Administration (FDA) approved small molecules. Recent interactive datasets have enabled users to interface more readily with cysteine chemoproteomics datasets. However, these resources remain limited to single studies and therefore do not provide a mechanism to perform cross-study analyses. Here we report CysDB as a curated community-wide repository of human cysteine chemoproteomics data derived from nine high-coverage studies. CysDB is publicly available at https://backuslab.shinyapps.io/cysdb/ and features measures of identification for 62,888 cysteines (24% of the cysteinome), as well as annotations of functionality, druggability, disease relevance, genetic variation, and structural features. Most importantly, we have designed CysDB to incorporate new datasets to further support the continued growth of the druggable cysteinome. [Display omitted] •Comprehensive repository for human cysteine chemoproteomics data•Enrichment of ligandable cysteines in undruggable classes of proteins•Visualization of lead compounds for 9,246 cysteines•Web app includes annotations of functionality, druggability, and structural motifs Boatner et al. report the development of the CysDB resource, which provides annotations of function, human genetics, structure, and disease relevance for 24% of all cysteines the human proteome.