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) desferrioxamine B [300 uM] YPD hom 4,518 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) deferiprone [300 uM] YPD hom 4,518 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) calmidazolium [7 uM] YPD hom 4,493 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sphinganine [30 uM] YPD hom 4,483 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) trapoxin A [185 uM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3637) [1.5 uM] YPD hom 4,448 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3637) [2 uM] YPD hom 4,507 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3637) [2.5 uM] YPD hom 4,507 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3637) [3 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3637) [4.5 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3638) [3 uM] YPD hom 4,507 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3638) [4 uM] YPD hom 4,507 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3638) [5 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Valinomycin Derivative (CMB:3638) [7.5 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) chondramide [110 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) glucitol [650 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sodium chloride [360 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) potassium chloride [440 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) calcium dichloride [52 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ethylenediaminetetraacetic acid [100 uM] YPD hom 4,509 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ethylenediaminetetraacetic acid [120 uM] YPD hom 4,448 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ethylenediaminetetraacetic acid [180 uM] YPD hom 4,448 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sodium acetate [150 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) hydrogen chloride [70 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sodium hydroxide [10 mM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) glucose [0.5 uM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) glucose [0.75 uM] YPD hom 4,541 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) enniatin derivative [70 uM] YPD hom 4,511 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Lysolipin X [3 uM] YPD hom 4,554 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Lysolipin X [5 uM] YPD hom 4,554 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) tunicamycin B [0.2 uM] YPD hom 4,554 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) tunicamycin B [0.3 uM] YPD hom 4,554 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) X-206 [2 uM] YPD hom 4,539 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) nigericin [15 uM] YPD hom 4,503 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) bleomycin A2 [0.075 uM] YPD hom 4,554 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) phleomycin D1 [0.012 uM] YPD hom 4,514 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) phleomycin D1 [0.05 uM] YPD hom 4,542 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) phleomycin D1 [0.1 uM] YPD hom 4,539 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) phleomycin D1 [0.3 uM] YPD hom 4,539 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) mercury dichloride [50 uM] YPD hom 4,524 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) methylmercury(.) [0.25 uM] YPD hom 4,534 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) methylmercury(.) [0.5 uM] YPD hom 4,534 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) manganese(II) chloride [10 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) copper(II) sulfate [75 uM] YPD hom 4,525 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) copper(II) sulfate [120 uM] YPD hom 4,544 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) copper(II) sulfate [200 uM] YPD hom 4,544 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) amitriptyline [50 uM] YPD het 5,801 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Leucanicidin [21.081 uM] YPD het 5,791 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) strobilurin B [200 uM] YPD het 5,789 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) bafilomycin A1 [43.69 uM] YPD het 5,801 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.