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Updated: Jun 5, 2026

A Manual Small Molecule Screen Approaching High-throughput Using Zebrafish Embryos
Published on: November 8, 2014
Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action
Laura Kapitzky1, Pedro Beltrao, Theresa J Berens
1Department of Cellular and Molecular Pharmacology, QB3 Institute, University of California, San Francisco, CA 94158, USA.
Abstract:
We present a cross-species chemogenomic screening platform using libraries of haploid deletion mutants from two yeast species, Saccharomyces cerevisiae and Schizosaccharomyces pombe. We screened a set of compounds of known and unknown mode of action (MoA) and derived quantitative drug scores (or D-scores), identifying mutants that are either sensitive or resistant to particular compounds. We found that compound-functional module relationships are more conserved than individual compound-gene interactions between these two species. Furthermore, we observed that combining data from both species allows for more accurate prediction of MoA. Finally, using this platform, we identified a novel small molecule that acts as a DNA damaging agent and demonstrate that its MoA is conserved in human cells.
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