Welcome to the chemogenomics portal of CAPCA, a technology platform located in the Institut for Research in Immunology and Cancer (IRIC). We offer specialized services for the characterization of drug and bioactive compound mechanism-of-action based on genetic sensitization and resistance identified through CRISPR/Cas9 pooled screens with a custom genome-wide sgRNA library (Bertomeu et al., Mol Cell Biol. 2017). These services span a fully integrated pipeline that includes verification of compound identity and purity by analytical characterization, dose-response assessment of compound effect on cell profileration, parallized large-scale culture screens with a genome-wide sgRNA libraries, sample work-up, next-generation sequencing, and data analysis.
Chemical-gene interactions – manifest as the decreased or increased fitness of any given genetic mutant in the presence of a drug or other bioactive compound – reveal how a compound affects the genetic network of the cell. The complete set of such interactions forms a chemogenomic profile for a given compound in a given cell type. The growth of a human cell line pool that bears CRISPR/Cas9-generated indel clones for all human genes in the presence of a bioactive compound allows the systematic detection of chemical-gene interactions by changes in sgRNA barcode frequencies. Chemogenomic profiles can reveal compound mechanism-of-action, on- and off-target effects, and novel aspects of gene function at an unprecedented level of resolution.