Abstract
We systematically analyzed the relationships between gene fitness profiles (co-fitness) and drug inhibition profiles (co-inhibition) from several hundred chemogenomic screens in yeast. Co-fitness predicted gene functions distinct from those derived from other assays and identified conditionally dependent protein complexes. Co-inhibitory compounds were weakly correlated by structure and therapeutic class. We developed an algorithm predicting protein targets of chemical compounds and verified its accuracy with experimental testing. Fitness data provide a novel, systems-level perspective on the cell.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Algorithms*
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Cation Transport Proteins / metabolism
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Clozapine / pharmacology
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Copper Transport Proteins
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Drug Delivery Systems / methods
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Drug Resistance, Fungal / genetics
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Gene Deletion
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Genes, Fungal / drug effects
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Genes, Fungal / genetics*
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Genetic Fitness / genetics*
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Genome, Fungal / genetics*
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Genomics / methods*
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Membrane Proteins / metabolism
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Molecular Chaperones / metabolism
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Nocodazole / pharmacology
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae / growth & development
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Saccharomyces cerevisiae Proteins / metabolism
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Structure-Activity Relationship
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Systems Biology / methods*
Substances
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COX17 protein, S cerevisiae
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Cation Transport Proteins
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Copper Transport Proteins
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EXO84 protein, S cerevisiae
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Membrane Proteins
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Molecular Chaperones
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Saccharomyces cerevisiae Proteins
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Clozapine
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Nocodazole