title: Cross-species chemogenomic profiling reveals evolutionarily conserved drug mode of action.
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.
authors.affiliation: Department of Cellular and Molecular Pharmacology, QB3 Institute, University of California, San Francisco, CA 94158, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Kapitzky
authors.forename: Pedro
authors.initials: P
authors.lastname: Beltrao
authors.forename: Theresa J
authors.initials: TJ
authors.lastname: Berens
authors.forename: Nadine
authors.initials: N
authors.lastname: Gassner
authors.forename: Chunshui
authors.initials: C
authors.lastname: Zhou
authors.forename: Arthur
authors.initials: A
authors.lastname: Wüster
authors.forename: Julie
authors.initials: J
authors.lastname: Wu
authors.forename: M Madan
authors.initials: MM
authors.lastname: Babu
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Elledge
authors.forename: David
authors.initials: D
authors.lastname: Toczyski
authors.forename: R Scott
authors.initials: RS
authors.lastname: Lokey
authors.forename: Nevan J
authors.initials: NJ
authors.lastname: Krogan
mesh_terms: D000935:Antifungal Agents / Q000378:metabolism / Q000494:pharmacology*; D004249:DNA Damage; D025141:Drug Resistance, Fungal; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005800:Genes, Fungal; D016681:Genome, Fungal / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D016296:Mutagenesis; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D012568:Schizosaccharomyces / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D017384:Sequence Deletion
chemical_list: D000935:Antifungal Agents