Data from: High-resolution chemical dissection of a model eukaryote reveals targets, pathways and gene functions

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 (Ole1p and
Fas1p), 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 2-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.