ArticleMolecular systems biology2021
From chemoproteomic-detected amino acids to genomic coordinates: insights into precise multi-omic data integration.
Article in Molecular systems biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 24 citations in OpenAlex.
- CIAA: Integrated Proteomics and Structural Modeling for Understanding Cysteine Reactivity with Iodoacetamide Alkyne.ACS chemical biology · 2025Article
- Prioritizing disease-associated missense variants with chemoproteomic-detected amino acids.American journal of human genetics · 2025Article
- Proteome-wide ligandability maps of drugs with diverse cysteine-reactive chemotypes.Nature communications · 2025Article
- A platform for mapping reactive cysteines within the immunopeptidome.Nature communications · 2024Article
- Chemoproteogenomic stratification of the missense variant cysteinome.Nature communications · 2024Article
- Dual-Probe Activity-Based Protein Profiling Reveals Site-Specific Differences in Protein Binding of EGFR-Directed Drugs.ACS chemical biology · 2024Article
- Chemoproteomics Identifies State-Dependent and Proteoform-Selective Caspase-2 Inhibitors.Journal of the American Chemical Society · 2024Article
- Pervasive aggregation and depletion of host and viral proteins in response to cysteine-reactive electrophilic compounds.bioRxiv : the preprint server for biology · 2023Article
- Multi-omic stratification of the missense variant cysteinome.bioRxiv : the preprint server for biology · 2023Article
- CysDB: a human cysteine database based on experimental quantitative chemoproteomics.Cell chemical biology · 2023Article
- Engaging a Non-catalytic Cysteine Residue Drives Potent and Selective Inhibition of Caspase-6.Journal of the American Chemical Society · 2023Article
- New approaches to target RNA binding proteins.Current opinion in chemical biology · 2021Review
- From chemoproteomic-detected amino acids to genomic coordinates: insights into precise multi-omic data integration.Molecular systems biology · 2021Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The integration of proteomic, transcriptomic, and genetic variant annotation data will improve our understanding of genotype-phenotype associations. Due, in part, to challenges associated with accurate inter-database mapping, such multi-omic studies have not extended to chemoproteomics, a method that measures the intrinsic reactivity and potential "druggability" of nucleophilic amino acid side chains. Here, we evaluated mapping approaches to match chemoproteomic-detected cysteine and lysine residues with their genetic coordinates. Our analysis revealed that database update cycles and reliance on stable identifiers can lead to pervasive misidentification of labeled residues. Enabled by this examination of mapping strategies, we then integrated our chemoproteomics data with computational methods for predicting genetic variant pathogenicity, which revealed that codons of highly reactive cysteines are enriched for genetic variants that are predicted to be more deleterious and allowed us to identify and functionally characterize a new damaging residue in the cysteine protease caspase-8. Our study provides a roadmap for more precise inter-database mapping and points to untapped opportunities to improve the predictive power of pathogenicity scores and to advance prioritization of putative druggable sites.
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