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) sodium hydroxide [8 mM] YPD het 5,799 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) glucose [0.25 uM] YPD het 5,799 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) enniatin derivative [8 uM] YPD het 5,760 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) borrelidin [45 uM] YPD het 5,780 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Lysolipin X [2 uM] YPD het 5,807 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) tunicamycin B [0.15 uM] YPD het 5,781 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) squalestatin derivative [8 uM] YPD het 5,781 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) X-206 [1 uM] YPD het 5,786 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) trichothecene [3 uM] YPD het 5,779 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) nigericin [8 uM] YPD het 5,794 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) bleomycin A2 [0.05 uM] YPD het 5,807 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) elaiophylin [30 uM] YPD het 5,801 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) phleomycin D1 [0.01 uM] YPD het 5,786 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) mercury dichloride [35 uM] YPD het 5,773 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) tavaborole [0.5 uM] YPD het 5,821 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) manganese(II) chloride [5 uM] YPD het 5,807 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) copper(II) sulfate [50 uM] YPD het 5,807 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) doxorubicin [28.066 uM] YPD het 5,808 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) Ascosteroside [0.02 uM] YPD het 5,796 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) deferasirox [250 uM] YPD het 5,795 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) deferasirox [300 uM] YPD het 5,795 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) deferasirox [350 uM] YPD het 5,795 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) deferasirox [400 uM] YPD het 5,795 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) epothilon B derivative [15 uM] YPD het 5,798 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) epothilon B derivative [30 uM] YPD het 5,798 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ergokonin A [0.7 uM] YPD het 5,788 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) rapamycin derivative [0.015 uM] YPD het 5,782 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) rapamycin derivative [0.02 uM] YPD het 5,809 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) rapamycin derivative [0.03 uM] YPD het 5,782 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) dequalinium chloride [0.2 uM] YPD het 5,811 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) ravidomycin [10 uM] YPD het 5,786 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) SDZ 90-215 [4 uM] YPD het 5,788 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) SDZ 90-215 [6 uM] YPD het 5,788 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sinefungin [0.1 uM] YPD het 5,770 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sinefungin [1 uM] YPD het 5,806 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) sinefungin [1.5 uM] YPD het 5,806 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) triclosan [10 uM] YPD het 5,770 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) triclosan [15 uM] YPD het 5,794 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) radicicol [75 uM] YPD het 5,803 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) geldanamycin [150 uM] YPD het 5,772 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) quinacrine [180 uM] YPD het 5,802 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) chlorpromazine [12.5 uM] YPD het 5,802 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) curcumin [55 uM] YPD het 5,789 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) curcumin [70 uM] YPD het 5,789 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) curcumin [75 uM] YPD het 5,793 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) curcumin [85 uM] YPD het 5,789 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) cobalt dichloride [200 uM] YPD het 5,801 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) caffeine [1 mM] YPD het 5,791 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) caffeine [1.5 mM] YPD het 5,791 Quantitative
Hoepfner D~Movva NR, 2014 growth (relative abundance in pooled culture) caffeine [2 mM] YPD het 5,791 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.