CysDB: a human cysteine database based on experimental quantitative chemoproteomics.

Area of Science:

• Biochemistry
• Pharmacology
• Bioinformatics

Background:

• Cysteine chemoproteomics reveals the druggability of many cysteine residues, offering potential to target the ~96% of the human proteome currently untargeted by FDA-approved small molecules.
• Existing interactive datasets facilitate access to cysteine chemoproteomics data but are limited to single studies, hindering cross-study analysis.

Purpose of the Study:

• To develop CysDB, a curated, community-wide repository for human cysteine chemoproteomics data.
• To enable cross-study analysis and facilitate the expansion of the druggable cysteinome.

Main Methods:

• Compiled and curated data from nine high-coverage human cysteine chemoproteomics studies.
• Integrated identification measures for 62,888 cysteines (24% of the cysteinome).
• Annotated cysteines with functionality, druggability, disease relevance, genetic variation, and structural features.

Main Results:

• Established CysDB, a publicly accessible repository (https://backuslab.shinyapps.io/cysdb/).
• Included comprehensive data on 62,888 cysteines, significantly expanding the known druggable cysteinome.
• Provided rich annotations to contextualize cysteine properties and potential therapeutic relevance.

Conclusions:

• CysDB serves as a valuable, centralized resource for researchers investigating cysteine druggability.
• The repository is designed for future data integration, supporting the ongoing expansion of the druggable proteome.
• Facilitates drug discovery efforts by providing a unified platform for cysteine-focused chemoproteomics data.