Chemical probes are important tools for understanding biological systems. However, because of the huge combinatorial space of targets and potential compounds, traditional chemical screens cannot be applied systematically to find probes for all possible druggable targets. Here, we demonstrate a novel concept for overcoming this challenge by leveraging high-throughput metabolomics and overexpression to predict drug-target interactions. The metabolome profiles of yeast treated with 1,280 compounds from a chemical library were collected and compared with those of inducible yeast membrane protein overexpression strains. By matching metabolome profiles, we predicted which small molecules targeted which signaling systems and recovered known interactions. Drug-target predictions were generated across the 86 genes studied, including for difficult to study membrane proteins. A subset of those predictions were tested and validated, including the novel targeting of GPR1 signaling by ibuprofen. These results demonstrate the feasibility of predicting drug-target relationships for eukaryotic proteins using high-throughput metabolomics.
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| Evidence ID | Analyze ID | Gene/Complex | Systematic Name/Complex Accession | Qualifier | Gene Ontology Term ID | Gene Ontology Term | Aspect | Annotation Extension | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Phenotype | Experiment Type | Experiment Type Category | Mutant Information | Strain Background | Chemical | Details | Reference |
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| Evidence ID | Analyze ID | Gene | Gene Systematic Name | Disease Ontology Term | Disease Ontology Term ID | Qualifier | Evidence | Method | Source | Assigned On | Reference |
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| Evidence ID | Analyze ID | Regulator | Regulator Systematic Name | Target | Target Systematic Name | Direction | Regulation of | Happens During | Regulator Type | Direction | Regulation Of | Happens During | Method | Evidence | Strain Background | Reference |
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| Site | Modification | Modifier | Source | Reference |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Allele | Assay | Annotation | Action | Phenotype | SGA score | P-value | Source | Reference | Note |
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| Evidence ID | Analyze ID | Interactor | Interactor Systematic Name | Interactor | Interactor Systematic Name | Assay | Annotation | Action | Modification | Source | Reference | Note |
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| Complement ID | Locus ID | Gene | Species | Gene ID | Strain background | Direction | Details | Source | Reference |
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| Evidence ID | Analyze ID | Dataset | Description | Keywords | Number of Conditions | Reference |
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| Evidence ID | Analyze ID | File | Description |
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