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Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action

Year: 2010
Type: article
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.
DOI: 10.1038/msb.2010.107
Authors: Laura Kapitzky, Pedro Beltrao, Theresa J Berens, Nadine Gassner, Chunshui Zhou, Arthur Wüster, Julie Wu, M Madan Babu, Stephen J Elledge, David Toczyski, R Scott Lokey, Nevan J Krogan
Institutions: QB3, University of California, San Francisco, University of California, Santa Cruz, Brigham and Women's Hospital, Howard Hughes Medical Institute, Harvard University, MRC Laboratory of Molecular Biology
Language: English
Open Access status: gold
Estimated APC paid: $7,990
OpenAlex ID: W2136740706
FWCI: 10.77
Cites: 52
Cited by: 160
Related to: 10