Hoepfner D~Movva NR, 2014

Pubmed ID 24360837
Title High-resolution chemical dissection of a model eukaryote reveals targets, pathways and gene functions.
Authors Dominic Hoepfner, Stephen B Helliwell, Heather Sadlish, Sven Schuierer, Ireos Filipuzzi, Sophie Brachat, Bhupinder Bhullar, Uwe Plikat, Yann Abraham, Marc Altorfer, Thomas Aust, Lukas Baeriswyl, Raffaele Cerino, Lena Chang, David Estoppey, Juerg Eichenberger, Mathias Frederiksen, Nicole Hartmann, Annika Hohendahl, Britta Knapp, Philipp Krastel, Nicolas Melin, Florian Nigsch, Edward J Oakeley, Virginie Petitjean, Frank Petersen, Ralph Riedl, Esther K Schmitt, Frank Staedtler, Christian Studer, John A Tallarico, Stefan Wetzel, Mark C Fishman, Jeffrey A Porter, N Rao Movva
Abstract Due to evolutionary conservation of biology, experimental knowledge captured from genetic studies in eukaryotic model organisms provides insight into human cellular pathways and ultimately physiology. Yeast chemogenomic profiling is a powerful approach for annotating cellular responses to small molecules. Using an optimized platform, we provide the relative sensitivities of the heterozygous and homozygous deletion collections for nearly 1800 biologically active compounds. The data quality enables unique insights into pathways that are sensitive and resistant to a given perturbation, as demonstrated with both known and novel compounds. We present examples of novel compounds that inhibit the therapeutically relevant fatty acid synthase and desaturase (Fas1p and Ole1p), and demonstrate how the individual profiles facilitate hypothesis-driven experiments to delineate compound mechanism of action. Importantly, the scale and diversity of tested compounds yields a dataset where the number of modulated pathways approaches saturation. This resource can be used to map novel biological connections, and also identify functions for unannotated genes. We validated hypotheses generated by global two-way hierarchical clustering of profiles for (i) novel compounds with a similar mechanism of action acting upon microtubules or vacuolar ATPases, and (ii) an un-annotated ORF, YIL060w, that plays a role in respiration in the mitochondria. Finally, we identify and characterize background mutations in the widely used yeast deletion collection which should improve the interpretation of past and future screens throughout the community. This comprehensive resource of cellular responses enables the expansion of our understanding of eukaryotic pathway biology.
Citation Microbiol. Res. 2014 Feb-Mar; 169:107-20
Notes This study tested 1641 proprietary compounds (named CMBxxx) and 136 reference compounds with known modes of action. We only loaded the data for the 136 known compounds because proprietary compounds were not associated with any chemical structures, accession numbers or compound names (other than an internal ID number), thus preventing their follow-up analysis or validation.

Datasets

Download the list of datasets
Paper Phenotype Condition Medium Collection Tested mutants Data Details
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) amitriptyline [50 uM] YPD hom 4,518 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Leucanicidin [21.081 uM] YPD hom 4,521 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) strobilurin B [200 uM] YPD hom 4,502 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) bafilomycin A1 [43.69 uM] YPD hom 4,511 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) deferasirox [200 uM] YPD hom 4,516 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) epothilon B derivative [5 uM] YPD hom 4,523 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) trichostatin A [200 uM] YPD hom 4,501 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Graphinone [200 uM] YPD hom 4,532 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) myriocin derivative [8.119 uM] YPD hom 4,534 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) terbinafine [12.381 uM] YPD hom 4,518 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) cyproconazole [0.284 uM] YPD hom 4,518 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) enniatin derivative [27 uM] YPD hom 4,504 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) naftifine [70.999 uM] YPD hom 4,536 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ascomycin [100 uM] YPD hom 4,518 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ergokonin A [0.913 uM] YPD hom 4,532 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) concanamycin A [0.111 uM] YPD hom 4,532 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) rapamycin derivative [0.01 uM] YPD hom 4,528 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) dequalinium chloride [0.1 uM] YPD hom 4,535 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) voriconazole [0.528 uM] YPD hom 4,501 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) (-)-anisomycin [10 uM] YPD hom 4,530 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ravidomycin [12.745 uM] YPD hom 4,516 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Enniatin B1 [90 uM] YPD hom 4,508 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) SDZ 90-215 [3 uM] YPD hom 4,506 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sinefungin [0.02 uM] YPD hom 4,493 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) boromycin [4 uM] YPD hom 4,508 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) echinocandin B derivative [0.01 uM] YPD hom 4,521 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) triclosan [6 uM] YPD hom 4,493 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) benzethonium chloride [14 uM] YPD hom 4,540 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) diazaborine [23.379 uM] YPD hom 4,521 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) fluvastatin sodium [57.186 uM] YPD hom 4,521 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) tubulozole [0.5 uM] YPD hom 4,517 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) radicicol [88.72 uM] YPD hom 4,521 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) geldanamycin [200 uM] YPD hom 4,514 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) quinacrine [200 uM] YPD hom 4,569 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) chlorpromazine [25.284 uM] YPD hom 4,501 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) methotrexate [200 uM] YPD hom 4,565 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) benomyl [57.746 uM] YPD hom N/A Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) curcumin [58.546 uM] YPD hom 4,589 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) cobalt dichloride [92.63 uM] YPD hom 4,511 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) caffeine [500 uM] YPD hom 4,755 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sirolimus [1 nM] YPD hom 4,516 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) staurosporine [1.088 uM] YPD hom 4,497 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) zaragozic acid A [13.625 uM] YPD hom 4,497 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) hydroxyurea [16.6 mM] YPD hom 4,563 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) actinomycin D [75.238 uM] YPD hom 4,524 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Amiodarone hydrochloride [13.430 uM] YPD hom 4,571 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) trifluoperazine hydrochloride [7.3 uM] YPD hom 4,576 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) clotrimazole [0.471 uM] YPD hom 4,524 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) camptothecin [200 uM] YPD hom 4,520 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) fenpropimorph [0.273 uM] YPD hom 4,524 Quantitative

Curation history

Data

April 11, 2014 Ready to load.
May 18, 2016 Loaded.

Tested strains

April 11, 2014 Ready to load.
May 18, 2016 Loaded.