Systematic analysis of genome-wide fitness data in yeast reveals novel gene function and drug action
Open accessAbstract
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.
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The molecular target of psychoactive drugs drofenine, clozapine, propiomazine, and metergoline was suggested to be the small ribosomal subunit and cytochrome c oxidase (COX17).
“For example, following this approach, the molecular target of psychoactive drugs, such as drofenine, clozapine, propiomazine, and metergoline, were suggested to be small ribosomal subunit and cytochrome c oxidase (COX17), the terminal component of the mitochondrial respiratory chain [17].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [17]
In S. cerevisiae, the small ribosomal subunit and cytochrome c oxidase are targets of psychoactive drugs.
“Hillenmeyer et al. reported that, in the same microbe, the small ribosomal subunit and cytochrome c oxidase are the targets of psychoactive drugs [17].”
From Antimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications (2021) · cites this paper as [17]
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Global landscape of protein complexes in the yeast Saccharomyces cerevisiae
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MethodProteome survey reveals modularity of the yeast cell machinery
Gavin, A., Aloy, P., Grandi, P., Krause, R., Böesche, M., Marzioch, M., Rau, C., Jensen, L. J., Bastuck, S., Dümpelfeld, B., et al. (2006) · Nature · doi:10.1038/nature04532 · Cited by 2,544 · cited 1× · see citing works
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MethodFunctional Discovery via a Compendium of Expression Profiles
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Tong, A. H. Y., Lesage, G., Bader, G. D., Ding, H., Xu, H., Xin, X., Young, J., Berriz, G. F., Brost, R. L., Chang, M., et al. (2004) · Science · doi:10.1126/science.1091317 · Cited by 2,070 · cited 1× · see citing works
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MethodA Critical Assessment of Docking Programs and Scoring Functions
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“Detailed biochemical characterization will be required to elucidate the exact nature of this interaction which, based on renewed interest in clozapine [49], is of great medical value.”
BackgroundCell-signalling dynamics in time and space
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“The fact that signal transduction is predicted relatively well by co-fitness, for example, may be explained by the fact that signal transduction is often a rapid response occurring on the order of milliseconds, a time frame too short to allow expression and translation of required proteins [53,54].”
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BackgroundMethodPrediction of drug–target interaction networks from the integration of chemical and genomic spaces
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The Chemical Genomic Portrait of Yeast: Uncovering a Phenotype for All Genes
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“For example, some antifungal azole drugs such as miconazole inhibit several hundred strains, only one of which is deleted for the known target ERG11, (Figure 2) [1].”
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MethodThe Exocyst is a multiprotein complex required for exocytosis in Saccharomyces cerevisiae.
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“Our preliminary genetic data indicating a novel interaction between Cox17 and clozapine are tantalizing given the renewed interest in this drug [61], and deserve further investigation.”
BackgroundDo Structurally Similar Molecules Have Similar Biological Activity?
Martin, Y. C., Kofron, J. L., & Traphagen, L. M. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020155c · Cited by 806 · cited 1× · see citing works
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BackgroundToward a Comprehensive Atlas of the Physical Interactome of Saccharomyces cerevisiae
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MethodA Probabilistic Functional Network of Yeast Genes
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“A related approach employs gene-deletion fitness profiling, where the growth profiles of haploid deletion strains in the presence of drug are compared to growth profiles obtained in the presence of a second deletion [5].”
BackgroundMethodMapping Pathways and Phenotypes by Systematic Gene Overexpression
Sopko, R., Huang, D., Preston, N., Chua, G., Papp, B., Kafadar, K. A., Snyder, M., Oliver, S. G., Cyert, M., Hughes, T. R., et al. (2006) · Molecular Cell · doi:10.1016/j.molcel.2005.12.011 · Cited by 650 · cited 1× · see citing works
“Second, the 'rescuing protein' must be expressed at a level that can override the compound effect, but not expressed to a level that will inhibit yeast growth [48], which would therefore confound the detection of growth rescue.”
BackgroundPrediction of Protein−Ligand Interactions. Docking and Scoring: Successes and Gaps
Leach, A. R., Shoichet, B. K., & Peishoff, C. E. (2006) · Journal of Medicinal Chemistry · doi:10.1021/jm060999m · Cited by 648 · see citing works
Genomic profiling of drug sensitivities via induced haploinsufficiency
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Self-citationGasch, A. P., Huang, M., Metzner, S., Botstein, D., Elledge, S. J., & Brown, P. O. (2001) · Molecular Biology of the Cell · doi:10.1091/mbc.12.10.2987 · Cited by 542 · cited 1× · see citing works
“Functional prediction performance was compared using several types of functional yeast assays: co-fitness; a unified protein-protein interaction network [25] derived from two large-scale affinity precipitation studies [26,27]; synthetic lethality [28]; and co-expression over three microarray gene expression studies [2…”
MethodMechanisms of Haploinsufficiency Revealed by Genome-Wide Profiling in Yeast
Deutschbauer, A. M., Jaramillo, D. F., Proctor, M., Kumm, J., Hillenmeyer, M. E., Davis, R. W., Nislow, C., & Giaever, G. (2005) · Genetics · doi:10.1534/genetics.104.036871 · Cited by 535 · cited 4× · see citing works
“Phenotype in rich medium (one feature) In the absence of drug, if the homozygous deletion strain gi initially showed no phenotype relative to wild type [9,78], the target cannot be identified by the heterozygous deletion assay as this assay is dependent on diminished 'functional dosage' of the drug target based on gro…”
BackgroundMethodInfluentialSelf-citationTroyanskaya, O. G., Dolinski, K. J., Owen, A. B., Altman, R. B., & Botstein, D. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0832373100 · Cited by 528 · cited 2× · see citing works
“Regardless of the underlying reasons why co-fitness performs better for certain functions, this metric clearly provides distinct information that, when integrated with diverse data sources, will aid the development of tools designed to predict gene function [11,12].”
BackgroundChemogenomic profiling: Identifying the functional interactions of small molecules in yeast
Giaever, G. N., Flaherty, P., Kumm, J., Proctor, M. J., Nislow, C., Jaramillo, D. F., Chu, A. M., Jordan, M. I., Arkin, A. P., & Davis, R. W. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0307490100 · Cited by 506 · cited 7× · see citing works
“With this comprehensive analysis of the chemogenomic fitness assay results, we asked to what degree the assay could systematically predict drug targets [2-4].”
BackgroundMethodInfluentialSelf-citationExploring the Mode-of-Action of Bioactive Compounds by Chemical-Genetic Profiling in Yeast
Parsons, A. B., López, A., Givoni, I. E., Williams, D. E., Gray, C. A., Porter, J., Chua, G., Sopko, R., Brost, R. L., Ho, C.-H., et al. (2006) · Cell · doi:10.1016/j.cell.2006.06.040 · Cited by 500 · cited 2× · see citing works
“This assay identifies genes required for growth in the presence of compound, often identifying functions that buffer the drug target pathway [5-8].”
BackgroundBiochemical and genetic analysis of the yeast proteome with a movable ORF collectionPreprint
Gelperin, D. M., White, M. A., Wilkinson, M. L., Kon, Y., Kung, L. A., Wise, K. J., Lopez-Hoyo, N., Jiang, L., Piccirillo, S., Yu, H., et al. (2005) · Genes & Development · doi:10.1101/gad.1362105 · Cited by 479 · cited 1× · see citing works
“COX17 overexpression To create the overexpression strains, yeast strain Y258 (MATa pep4-3, his4-580, ura 3-53, leu2-3,112 [81]) was transformed with plasmids BG1805 (Open Biosystems, Huntsville, AL, USA): the vector is derived from pRSAB1234 from Erin O'Shea using sequence verified, de novo synthesized yeast or human…”
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“Of these, 134 interactions were due to only two of the DrugBank compounds, staurosporine and emodin, which have many annotated human kinase targets, each of which had up to several BLASTp-determined homologs in yeast.”
MethodInfluentialLum, P. Y., Armour, C. D., Stepaniants, S. B., Cavet, G., Wolf, M. K., Butler, J. S., Hinshaw, J. C., Garnier, P., Prestwich, G. D., Leonardson, A. S., et al. (2004) · Cell · doi:10.1016/s0092-8674(03)01035-3 · Cited by 471 · cited 4× · see citing works
“With this comprehensive analysis of the chemogenomic fitness assay results, we asked to what degree the assay could systematically predict drug targets [2-4].”
BackgroundInfluentialMolecular basis of resistance to azole antifungals.
Lupetti, A. (2002) · Trends in Molecular Medicine · doi:10.1016/s1471-4914(02)02280-3 · Cited by 449 · cited 7× · see citing works
“Kontoyiannis DP, Sagar N, Hirschi KD: Overexpression of Erg11p by the regulatable GAL1 promoter confers fluconazole resistance in Saccharomyces cerevisiae.”
BackgroundInfluentialZotenko, E., Mestre, J., O’Leary, D. P., & Przytycka, T. M. (2008) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000140 · Cited by 401 · cited 2× · see citing works
“On average, 40% of an essential gene's significantly co-fit partners were also essential genes, compared to only 23% for non-essential gene's co-fit partners (P 37 ,38].”
BackgroundCorrelated sequence-signatures as markers of protein-protein interaction
Sprinzak, E., & Margalit, H. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4920 · Cited by 401 · cited 1× · see citing works
“We calculated whether the set Ci was statistically enriched for any shared motif m, using a log risk ratio (RR), which has been applied in calculating other types of motif enrichment [79]:”
MethodProtein-ligand interaction prediction: an improved chemogenomics approach
Jacob, L., & Vert, J. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn409 · Cited by 382 · cited 1× · see citing works
“Other computational methods utilize protein sequence rather than chemical structure, but these methods are only applicable to individual proteins or a small subset of proteins that possess a high degree of similarity [ 58-60 ].”
MethodDefining transcription modules using large-scale gene expression data
Ihmels, J., Bergmann, S., & Barkai, N. (2004) · Bioinformatics · doi:10.1093/bioinformatics/bth166 · Cited by 338 · cited 1× · see citing works
“Two more distance metrics were calculated across subsets of experiments, based on a biclustering analysis on the log2 ratios, using the BicAT toolbox [68] with the Iterative Signature Algorithm [69].”
MethodA global view of pleiotropy and phenotypically derived gene function in yeast
Dudley, A. M., Janse, D. M., Tanay, A., Ron Shamir, A., & Church, G. M. (2005) · Molecular Systems Biology · doi:10.1038/msb4100004 · Cited by 330 · see citing works
BicAT: a biclustering analysis toolbox
Barkow‐Oesterreicher, S., Stefan Bleuler, A., Prelić, A., Philip Zimmermann, B., & Zitzler, E. (2006) · Bioinformatics · doi:10.1093/bioinformatics/btl099 · Cited by 273 · cited 1× · see citing works
“Two more distance metrics were calculated across subsets of experiments, based on a biclustering analysis on the log2 ratios, using the BicAT toolbox [68] with the Iterative Signature Algorithm [69].”
MethodA high-accuracy consensus map of yeast protein complexes reveals modular nature of gene essentiality
Hart, T., Lee, I., & Marcotte, E. M. (2007) · BMC Bioinformatics · doi:10.1186/1471-2105-8-236 · Cited by 269 · cited 3× · see citing works
“Indeed, if we define a complex as essential if >80% of its members are essential, 68 of 312 complexes are essential in rich medium, which is significantly greater than that expected by chance [14].”
BackgroundThe exocyst complex binds the small GTPase RalA to mediate filopodia formation
Sugihara, K., Asano, S., Tanaka, K., Iwamatsu, A., Okawa, K., & Ohta, Y. (2002) · Nature Cell Biology · doi:10.1038/ncb720 · Cited by 258 · cited 1× · see citing works
“The mammalian homolog is essential for development and participates in multiple biological processes, including vesicle targeting to the plasma membrane, protein translation, and filopodia extension [62,63].”
BackgroundTargeted selection of recombinant clones through gene dosage effects.
Rine, J., Hansen, W., Hardeman, E. C., & Davis, R. W. (1983) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.80.22.6750 · Cited by 252 · cited 1× · see citing works
“Intuitively, if the protein is a bona fide target of the compound, decreasing gene dosage should increase sensitivity to compound (as in the HIP assay) by decreasing the amount of target protein, and increasing gene dosage should increase resistance to compound through overexpression of the target protein [21].”
BackgroundSelf-citationYeast ABC transporters – A tale of sex, stress, drugs and aging
Jungwirth, H., & Kuchler, K. (2005) · FEBS Letters · doi:10.1016/j.febslet.2005.12.050 · Cited by 230 · cited 1× · see citing works
“Other genes required for uncompromised growth in these antifungals include multi-drug resistance genes, such as the drug transporter PDR5 (the yeast homolog of human MDR1), the lipid transporter PDR16, and the transcription factor PDR1, which regulates both PDR5 and PDR16 expression [41].”
BackgroundFinding function: evaluation methods for functional genomic data
Myers, C. L., Barrett, D. R., Hibbs, M., Huttenhower, C., & Troyanskaya, O. G. (2006) · BMC Genomics · doi:10.1186/1471-2164-7-187 · Cited by 211 · cited 6× · see citing works
“We first showed that, overall, co-fitness data identify gene function better than co-expression data but not as well as the physical interaction dataset when compared to a gold standard [13].”
BackgroundMethodInfluentialComparison of Automated Docking Programs as Virtual Screening Tools
Cummings, M. D., DesJarlais, R. L., Gibbs, A. C., Mohan, V., & Jaeger, E. P. (2005) · Journal of Medicinal Chemistry · doi:10.1021/jm049798d · Cited by 208 · cited 1× · see citing works
“The success of these methods to date has been variable, with some studies able to predict known interactions with significant enrichment, and others performing worse than random [55-57].”
BackgroundAn integrated platform of genomic assays reveals small-molecule bioactivities
Hoon, S. S., Smith, A. M., Wallace, I. M., Suresh, S., Miranda, M., Fung, E., Proctor, M. J., Shokat, K. M., Zhang, C., Davis, R. W., et al. (2008) · Nature Chemical Biology · doi:10.1038/nchembio.100 · Cited by 201 · cited 3× · see citing works
“This rationale has been used with success in a study of 188 compounds [23].”
BackgroundMethodSelf-citationSAR Index: Quantifying the Nature of Structure−Activity Relationships
Peltason, L., & Bajorath, J. (2007) · Journal of Medicinal Chemistry · doi:10.1021/jm0705713 · Cited by 201 · cited 1× · see citing works
“This finding can be attributed to structurally diverse compounds that inhibit different proteins within the same pathway, or to different compound structures that inhibit the same target [ 45 ,46].”
BackgroundGenome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents
Lee, W., St.Onge, R. P., Proctor, M. J., Flaherty, P., Jordan, M. I., Arkin, A. P., Davis, R. W., Nislow, C., & Giaever, G. N. (2005) · PLoS Genetics · doi:10.1371/journal.pgen.0010024 · Cited by 163 · cited 1× · see citing works
“In this way, fitness data allow identification of the potential drug target [3,4,10].”
BackgroundSelf-citationBackup without redundancy: genetic interactions reveal the cost of duplicate gene loss
Ihmels, J., Collins, S. R., Schuldiner, M., Krogan, N. J., & Weissman, J. S. (2007) · Molecular Systems Biology · doi:10.1038/msb4100127 · Cited by 151 · cited 2× · see citing works
“This finding supports the hypothesis of partial, rather than strict, redundancy [35].”
ResultRollema, H., Skolnik, M., d’Engelbronner, J. C., Igarashi, K., Usuki, E., & Castagnoli, N. (1994) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)38487-9 · Cited by 123 · cited 1× · see citing works
“This COX alteration has been shown to be linked to clozapine's side effects [66,67].”
BackgroundThe extensive and condition-dependent nature of epistasis among whole-genome duplicates in yeastPreprint
Musso, G. A., Costanzo, M., Huangfu, M., Smith, A. M., Paw, J., Luis, B.-J. S., Boone, C. M., Giaever, G. N., Nislow, C., Emili, A., et al. (2008) · Genome Research · doi:10.1101/gr.076174.108 · Cited by 121 · cited 1× · see citing works
“Consistent with other recent studies [35, 36 ], our finding supports models that posit that such genes are partially redundant, with deletion of either duplicate resulting in a similar (that is, co-fit) phenotype.”
ResultSelf-citationA Genome-Wide Overexpression Screen in Yeast for Small-Molecule Target Identification
Luesch, H., Wu, T. Y.-H., Ren, P., Gray, N. S., Schultz, P. G., & Supek, F. (2005) · Chemistry & Biology · doi:10.1016/j.chembiol.2004.10.015 · Cited by 112 · cited 1× · see citing works
“Finally, over-expression profiling is an approach to drug target identification that relies on the concept that overexpression of a drug target should confer resistance to a compound [21-23].”
BackgroundA Complex-based Reconstruction of the Saccharomyces cerevisiae Interactome
Wang, H., Kakaradov, B., Collins, S. R., Karotki, L., Fiedler, D., Shales, M., Shokat, K. M., Walther, T. C., Krogan, N. J., & Koller, D. (2009) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m800490-mcp200 · Cited by 106 · cited 2× · see citing works
“Recent analyses [14,15] show that proteins that are essential in rich medium tend to cluster into complexes, suggesting that essentiality is, to a large extent, a property of the entire complex.”
BackgroundSelf-citationLipschutz, J. H., Lingappa, V. R., & Mostov, K. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m213210200 · Cited by 99 · cited 1× · see citing works
“The mammalian homolog is essential for development and participates in multiple biological processes, including vesicle targeting to the plasma membrane, protein translation, and filopodia extension [62,63].”
BackgroundGENOME-WIDE RESPONSES TO DNA-DAMAGING AGENTS
Fry, R. C., Begley, T. J., & Samson, L. D. (2005) · Annual Review of Microbiology · doi:10.1146/annurev.micro.59.031805.133658 · Cited by 95 · cited 2× · see citing works
“Yeast competitive fitness data constitute a unique, genome-wide assay of the cellular response to environmental and chemical perturbations [ 1-8 ].”
BackgroundOff-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast
Ericson, E., Gebbia, M., Heisler, L. E., Wildenhain, J., Tyers, M., Giaever, G., & Nislow, C. (2008) · PLoS Genetics · doi:10.1371/journal.pgen.1000151 · Cited by 89 · cited 1× · see citing works
“Because their neurological targets do not exist in yeast, the sensitivity we observe is likely a result of these compounds affecting additional cellular targets in yeast [44]; these 'secondary' targets, if conserved, may correspond to additional targets of these compounds in human cells.”
BackgroundSelf-citationDimster-Denk, D., Rine, J., Phillips, J., Scherer, S., Cundiff, P., DeBord, K. L., Gilliland, D., Hickman, S., Jarvis, A., Tong, L., et al. (1999) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)32120-9 · Cited by 84 · see citing works
The Mammalian Exocyst, a Complex Required for Exocytosis, Inhibits Tubulin Polymerization
Wang, S., Liu, Y., Adamson, C. L., Valdez, G., Guo, W., & Hsu, S. C. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313778200 · Cited by 68 · cited 2× · see citing works
“It is known that the microtubule-depolymerizer nocodazole distorts the filamentous localization of Exo84 in cultured mammalian cells [64].”
Backgroundanatomical therapeutic chemical classification system (ATC)
Nahler, G. (2009) · Dictionary of Pharmaceutical Medicine · doi:10.1007/978-3-211-89836-9_64 · Cited by 67 · see citing works
Chemical genomic profiling to identify intracellular targets of a multiplex kinase inhibitor
Kung, C. K.-H., Kenski, D. M., Dickerson, S. H., Howson, R. W., Kuyper, L. F., Madhani, H. D., & Shokat, K. M. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407170102 · Cited by 61 · cited 1× · see citing works
“For example, one class of methods [19,20] searches for similarity of RNA expression profiles after drug exposure to profiles resulting from a conditional or complete gene deletion.”
BackgroundNagamine, N., Shirakawa, T., Minato, Y., Torii, K., Kobayashi, H., Imoto, M., & Sakakibara, Y. (2009) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1000397 · Cited by 58 · cited 1× · see citing works
“Other computational methods utilize protein sequence rather than chemical structure, but these methods are only applicable to individual proteins or a small subset of proteins that possess a high degree of similarity [58-60].”
MethodKontoyiannis, D. P., Sagar, N., & Hirschi, K. D. (1999) · Antimicrobial Agents and Chemotherapy · doi:10.1128/aac.43.11.2798 · Cited by 56 · see citing works
The First Two Cantharidin Analogues Displaying PP1 Selectivity
McCluskey, A., Keane, M. A., Walkom, C., Bowyer, M. C., Sim, A. T. R., Young, D. J., & Sakoff, J. A. (2002) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/s0960-894x(01)00777-6 · Cited by 56 · cited 1× · see citing works
“[23] and others in the literature [23,51,52], we find that 5 of our 12 top compound-target predictions were validated (Supplementary Table 1 in Additional file 1).”
BackgroundYokoyama, H., Kasai, N., Ueda, Y., Ryuji, N. I. W. A., Konaka, R., Mori, N., Tsuchihashi, N., Matsue, T., Ohya‐Nishiguchi, H., & Kamada, H. (1998) · Free Radical Biology and Medicine · doi:10.1016/s0891-5849(97)00435-8 · Cited by 46 · cited 1× · see citing works
“This COX alteration has been shown to be linked to clozapine's side effects [66,67].”
BackgroundPrince, J. A., Yassin, M. S., & Oreland, L. (1998) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(97)00036-9 · Cited by 31 · cited 1× · see citing works
“thought to be neurotransmitter receptors, but the drug also alters cytochome C oxidase (COX) activity through an unknown mechanism [65].”
BackgroundWulf, P. D., Brambilla, L., Vanoni, M., Porro, D., & Alberghina, L. (2000) · Journal of Microbiological Methods · doi:10.1016/s0167-7012(00)00176-7 · Cited by 23 · cited 1× · see citing works
“The fact that signal transduction is predicted relatively well by co-fitness, for example, may be explained by the fact that signal transduction is often a rapid response occurring on the order of milliseconds, a time frame too short to allow expression and translation of required proteins [53,54].”
BackgroundChen, X. J. (2001) · Journal of Bacteriology · doi:10.1128/jb.183.13.3939-3948.2001 · Cited by 22 · cited 1× · see citing works
“Combining our overexpression rescue results with those of Hoon et al. [23] and others in the literature [23, 51 ,52], we find that 5 of our 12 top compound-target predictions were validated (Supplementary Table 1 in Additional file 1). For the purposes of comparison, Hoon et al. [23] found overexpression resistance fo…”
ResultPache, R. A., Babu, M. M., & Aloy, P. (2009) · BMC Systems Biology · doi:10.1186/1752-0509-3-74 · Cited by 17 · see citing works
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Mutant phenotypes for thousands of bacterial genes of unknown function
Price, M. N., Wetmore, K. M., Waters, R. J., Callaghan, M., Ray, J., Liu, H., Kuehl, J. V., Melnyk, R. A., Lamson, J. S., Suh, Y., et al. (2018) · Nature · doi:10.1038/s41586-018-0124-0 · Cited by 576 · see citing works
Wetmore, K. M., Price, M. N., Waters, R. J., Lamson, J. S., He, J., Hoover, C. A., Blow, M. J., Bristow, J. D., Butland, G. P., Arkin, A. P., et al. (2015) · mBio · doi:10.1128/mbio.00306-15 · Cited by 474 · see citing works
“cerevisiae (16, 17) and hundreds have been performed in the bacteria Shewanella oneidensis MR-1 and Zymomonas mobilis ZM4 (1), far more than have been done with TnSeq approaches to date.”
BackgroundData mining in the Life Sciences with Random Forest: a walk in the park or lost in the jungle?
Touw, W. G., Bayjanov, J. R., Overmars, L., Backus, L., Boekhorst, J., Wels, M., & van Hijum, S. A. F. T. (2012) · Briefings in Bioinformatics · doi:10.1093/bib/bbs034 · Cited by 451 · see citing works
Combining Drug and Gene Similarity Measures for Drug-Target Elucidation
Perlman, L., Gottlieb, A., Atias, N., Ruppin, E., & Sharan, R. (2011) · Journal of Computational Biology · doi:10.1089/cmb.2010.0213 · Cited by 215 · see citing works
“Last, a recent approach used information on compound-induced fitness defects of yeast deletion strains to predict drug-targets in S. cerevisiae (Hillenmeyer et al., 2010).”
Schwarzmüller, T., Ma, B., Hiller, E., Istel, F., Tscherner, M., Brunke, S., Ames, L., Firon, A., Green, B., Cabral, V., et al. (2014) · PLoS Pathogens · doi:10.1371/journal.ppat.1004211 · Cited by 191 · see citing works
“These approaches also unraveled stress response mechanisms and provided new insights into drug susceptibility and morphogenesis [42–49].”
BackgroundA gene ontology inferred from molecular networks
Dutkowski, J., Kramer, M., Surma, M. A., Balakrishnan, R., Cherry, J. M., Krogan, N. J., & Ideker, T. (2013) · Nature Biotechnology · doi:10.1038/nbt.2463 · Cited by 184 · see citing works
Cross‐species chemogenomic profiling reveals evolutionarily conserved drug mode of action
Kapitzky, L., Beltrão, P., Berens, T. J., Gassner, N. C., Zhou, C., Wüster, A., Wu, J. T.-Y., Babu, M. M., Elledge, S. J., Toczyski, D. P., et al. (2010) · Molecular Systems Biology · doi:10.1038/msb.2010.107 · Cited by 160 · see citing works
“Additionally, comparing drug profiles makes it possible to infer the MoA of a drug of interest by the similarity of its chemogenomic profile to profiles of drugs with known MoA (Hillenmeyer et al, 2008, 2010).”
BackgroundHoepfner, D., Helliwell, S. B., Sadlish, H., Schuierer, S., Filipuzzi, I., Brachat, S., Bhullar, B., Plikat, U., Abraham, Y., Altorfer, M., et al. (2014) · Microbiological Research · doi:10.1016/j.micres.2013.11.004 · Cited by 166 · see citing works
Liu, H., Shiver, A. L., Price, M. N., Carlson, H. K., Trotter, V. V., Chen, Y., Escalante, V., Ray, J., Hern, K. E., Petzold, C. J., et al. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108789 · Cited by 161 · see citing works
“The development of large, multi-condition gene-phenotype datasets has proven useful for inferring gene function in a broad range of organisms (Deutschbauer et al., 2011; Hillenmeyer et al., 2010; Nichols et al., 2011), although this approach has not been applied to gut commensals.”
Functional genomics of lipid metabolism in the oleaginous yeast Rhodosporidium toruloides
Coradetti, S. T., Pinel, D., Geiselman, G. M., Ito, M., Mondo, S. J., Reilly, M. C., Cheng, Y.-F., Bauer, Š., Grigoriev, I. V., Gladden, J. M., et al. (2018) · eLife · doi:10.7554/elife.32110 · Cited by 134 · see citing works
Mitochondrial Electron Transport Is the Cellular Target of the Oncology Drug Elesclomol
Blackman, R. K., Cheung-Ong, K., Gebbia, M., Proia, D. A., He, S., Kepros, J., Jonneaux, A., Marchetti, P., Kluza, J., Rao, P. E., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0029798 · Cited by 132 · see citing works
Self-citationDeutschbauer, A. M., Price, M. N., Wetmore, K. M., Shao, W., Baumohl, J. K., Xu, Z., Nguyen, M., Kuehn, R., Davis, R. W., & Arkin, A. P. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002385 · Cited by 114 · see citing works
“By correlating genes with their phenotypes, a specific gene function can often be inferred [7,8,9,10].”
BackgroundSelf-citationMetabolomics Response for Drought Stress Tolerance in Chinese Wheat Genotypes (Triticum aestivum)
Guo, X., Xin, Z., Yang, T., Ma, X., Zhang, Y., Wang, Z., Ren, Y., & Lin, T. (2020) · Plants · doi:10.3390/plants9040520 · Cited by 114 · see citing works
Dissecting a complex chemical stress: chemogenomic profiling of plant hydrolysates
Skerker, J. M., Leon, D., Price, M. N., Mar, J. S., Tarjan, D. R., Wetmore, K. M., Deutschbauer, A. M., Baumohl, J. K., Bauer, Š., Ibáñez, A. B., et al. (2013) · Molecular Systems Biology · doi:10.1038/msb.2013.30 · Cited by 104 · see citing works
A mammalian functional-genetic approach to characterizing cancer therapeutics
Jiang, H., Pritchard, J. R., Williams, R. T., Lauffenburger, D. A., & Hemann, M. T. (2010) · Nature Chemical Biology · doi:10.1038/nchembio.503 · Cited by 104 · see citing works
“In this approach, bar-coded yeast deletion strains are exposed to select agents, and genotype-dependent drug sensitivity is used to identify genes and pathways affected by a given drug, as well as to develop a response signature that can be compared with other chemical or genetic perturbation”
Li, M., Xu, J., Wang, X., Fu, H., Zhao, M., Wang, H., & Shi, L. (2018) · Journal of Plant Physiology · doi:10.1016/j.jplph.2018.07.009 · Cited by 104 · see citing works
High-resolution network biology: connecting sequence with function
Ryan, C. J., Cimermančič, P., Szpiech, Z. A., Šali, A., Hernandez, R. D., & Krogan, N. J. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3574 · Cited by 98 · see citing works
“Similarly, others have integrated protein complexes with chemogenetic interactions to identify conditionally essential complexes 62 (the members of which all show negative interactions with a particular drug), which suggests that the function of the entire complex is required in the presence of…”
Cohesin Proteins Promote Ribosomal RNA Production and Protein Translation in Yeast and Human Cells
Bose, T., Lee, K. K., Lu, S., Xu, B., Harris, B. D., Slaughter, B. D., Unruh, J. R., Garrett, A. S., McDowell, W., Box, A., et al. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002749 · Cited by 97 · see citing works
“Growth curves were collected in triplicate for each genotype at time intervals of 15 min. We used a Tecan Infinite M200 Pro machine. Due to the non-linearity between optical density (OD) and cell number at higher cell densities, the measured Tecan ODs were converted to ‘real’ ODs using the calibration function ‘real O…”
MethodInfluentialHigh-Throughput Identification of Adaptive Mutations in Experimentally Evolved Yeast Populations
Payen, C., Sunshine, A. B., Ong, G. T., Pogachar, J. L., Zhao, W. D., & Dunham, M. J. (2016) · PLoS Genetics · doi:10.1371/journal.pgen.1006339 · Cited by 87 · see citing works
Predicting Adverse Drug Reactions Using Publicly Available PubChem BioAssay Data
Pouliot, Y., Chiang, A. P.-F., & Butte, A. J. (2011) · Clinical Pharmacology & Therapeutics · doi:10.1038/clpt.2011.81 · Cited by 80 · see citing works
Combining functional genomics and chemical biology to identify targets of bioactive compounds
Ho, C. H., Piotrowski, J., Dixon, S. J., Baryshnikova, A., Costanzo, M., & Boone, C. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.10.023 · Cited by 78 · see citing works
“As described above, drug-sensitive mutants often belong to pathways or complexes that function in parallel to the target of a specific compound [14,21,25,32].”
BackgroundFunctional genomics to uncover drug mechanism of action
Nijman, S. M. B. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1963 · Cited by 73 · see citing works
Metabolomics Response to Drought Stress in Morus alba L. Variety Yu-711
Ackah, M., Shi, Y., Wu, M., Wang, L., Peng, G., Guo, L., Xin, J., Li, S., Zhang, Q., Qiu, C., et al. (2021) · Plants · doi:10.3390/plants10081636 · Cited by 70 · see citing works
“Metabolomics has primarily focused on the organic molecular compounds (metabolites) found in or formed by organisms, tissues, and cells [23,24].”
BackgroundExtensive heterosis in growth of yeast hybrids is explained by a combination of genetic models
Shapira, R., Levy, T., Shaked, S., Fridman, E., & David, L. (2014) · Heredity · doi:10.1038/hdy.2014.33 · Cited by 70 · see citing works
Analysis of Chemical and Biological Features Yields Mechanistic Insights into Drug Side Effects
Duran‐Frigola, M., & Aloy, P. (2013) · Chemistry & Biology · doi:10.1016/j.chembiol.2013.03.017 · Cited by 57 · see citing works
“This assumption has permitted to relate targets showing similar pharmacological profiles (Garcia-Serna et al., 2010; Keiser et al., 2007; Mestres et al., 2006) into clusters of seemingly disparate proteins, providing new insights into the function of the targets (Hillenmeyer et al., 2010).”
BackgroundThe genetic control of growth rate: a systems biology study in yeast
Pir, P., Gutteridge, A., Wu, J., Rash, B. M., Kell, D. B., Zhang, N., & Oliver, S. G. (2012) · BMC Systems Biology · doi:10.1186/1752-0509-6-4 · Cited by 58 · see citing works
“Some of these pools have also been screened for haploinsufficiency when treated with drugs and sets of genes with drug sensitivity and resistance have been identified ([36-38]).”
BackgroundYeast as a model system for studying lipid homeostasis and function
Santos, A. X. S., & Riezman, H. (2012) · FEBS Letters · doi:10.1016/j.febslet.2012.07.033 · Cited by 56 · see citing works
“Chemical genomics is also a valuable approach to study the mechanism of action of bioactive chemicals that may have human therapeutic significance [121,128].”
BackgroundUthman, S., Bär, C., Scheidt, V., Liu, S., ten Have, S., Giorgini, F., Stark, M. J. R., & Schaffrath, R. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003334 · Cited by 56 · see citing works
“exploit yeast genome-wide genetic interaction and chemical genomics databases [43,44] to demonstrate that YLR143w (DPH6) and YBR246W (DPH7) cluster tightly with all known members of the diphthamide gene network.”
BackgroundMethodAntimicrobial Properties of Antidepressants and Antipsychotics—Possibilities and Implications
Caldara, M., & Marmiroli, N. (2021) · Pharmaceuticals · doi:10.3390/ph14090915 · Cited by 54 · see citing works
“For example, following this approach, the molecular target of psychoactive drugs, such as drofenine, clozapine, propiomazine, and metergoline, were suggested to be small ribosomal subunit and cytochrome c oxidase (COX17), the terminal component of the mitochondrial respiratory chain [17].”
BackgroundInfluentialTowards an Informative Mutant Phenotype for Every Bacterial Gene
Deutschbauer, A. M., Price, M. N., Wetmore, K. M., Tarjan, D. R., Xu, Z., Shao, W., Leon, D., Arkin, A. P., & Skerker, J. M. (2014) · Journal of Bacteriology · doi:10.1128/jb.01836-14 · Cited by 51 · see citing works
Zhang, Y., Ma, X., Wang, X., Liu, J., Huang, B., Guo, X., Xiong, S.-P., & La, G. (2016) · Plant Physiology and Biochemistry · doi:10.1016/j.plaphy.2016.11.009 · Cited by 52 · see citing works
Mast, F. D., Ratushny, A. V., & Aitchison, J. D. (2014) · The Journal of Cell Biology · doi:10.1083/jcb.201405027 · Cited by 51 · see citing works
“Structural, biochemical, and genetic evidence has revealed a modular NPC with eightfold symmetry (Alber et al., 2007; Hoelz et al., 2011).”
BackgroundMitochondrial Targets for Pharmacological Intervention in Human Disease
Malty, R. H., Jessulat, M., Jin, K., Musso, G. A., Vlasblom, J., Phanse, S., Zhang, Z., & Babu, M. (2014) · Journal of Proteome Research · doi:10.1021/pr500813f · Cited by 45 · see citing works
All or Nothing: Protein Complexes Flip Essentiality between Distantly Related Eukaryotes
Ryan, C. J., Krogan, N. J., Cunningham, P., & Cagney, G. (2013) · Genome Biology and Evolution · doi:10.1093/gbe/evt074 · Cited by 34 · see citing works
“…interactions (Segrè et al. 2005; Bandyopadhyay et al. 2008; Michaut et al. 2011), to display sensitivity to the same drugs (Fraser and Plotkin 2007; Hillenmeyer et al. 2010; Kapitzky et al. 2010), and to be associated with the same disease (Fraser and Plotkin 2007; Lage et al. 2007; Oti and…”
BackgroundNew Genes Involved in Osmotic Stress Tolerance in Saccharomyces cerevisiae
Gonzalez, R., Morales, P., Tronchoni, J., Cordero-Bueso, G. A., Vaudano, E. T., Quirós, M., Novo, M., Torres‐Pérez, R., & Valero, E. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01545 · Cited by 35 · see citing works
“Also, sorbitol 1M was used as one of the stress conditions in quantitative fitness analysis experiments, based on microarray technology (Hillenmeyer et al., 2010).”
MethodBlaby, I. K., Phillips, G., Blaby, C., Gulig, K. S., Yacoubi, B. E., & de Crécy‐Lagard, V. (2010) · Archaea · doi:10.1155/2010/426239 · Cited by 35 · see citing works
High-content screening of yeast mutant libraries by shotgun lipidomics
Tarassov, K., Stefanko, A., Casanovas, A., Surma, M. A., Berzina, Z., Hannibal‐Bach, H. K., Ekroos, K., & Ejsing, C. S. (2014) · Molecular BioSystems · doi:10.1039/c3mb70599d · Cited by 33 · see citing works
Chemogenomic approach identified yeast YLR143W as diphthamide synthetase
Su, X., Lin, Z., Chen, W., Jiang, H., Zhang, S., & Lin, H. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214346109 · Cited by 26 · see citing works
“The similarity of growth fitness under various conditions between any two different deletion strains has been calculated as the cofitness (15, 16).”
BackgroundProfiling of the effects of antifungal agents on yeast cells based on morphometric analysis
Gebre, A. A., Okada, H., Kim, C., Kubo, K., Ohnuki, S., & Ohya, Y. (2015) · FEMS Yeast Research · doi:10.1093/femsyr/fov040 · Cited by 25 · see citing works
From beer to breadboards: yeast as a force for biological innovation
Gaikani, H. K., Stolar, M., Kriti, D., Nislow, C., & Giaever, G. N. (2024) · Genome biology · doi:10.1186/s13059-023-03156-9 · Cited by 26 · see citing works
“HIP − HOP has been successfully used to identify the target of known and novel compounds [10, 106–109].”
MethodSelf-citationCalcineurin-dependent contributions to fitness in the opportunistic pathogen <i>Candida glabrata</i>
Pavesic, M. W., Gale, A. N., Nickels, T. J., Harrington, A. A., Bussey, M., & Cunningham, K. W. (2024) · mSphere · doi:10.1128/msphere.00554-23 · Cited by 22 · see citing works
Ong, W. K., Courtney, D. K., Pan, S., Andrade, R. B., Kiley, P. J., Pfleger, B. F., & Reed, J. L. (2020) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1008137 · Cited by 14 · see citing works
de Crécy‐Lagard, V., Forouhar, F., Brochier‐Armanet, C., Tong, L., & Hunt, J. F. (2012) · Biology Direct · doi:10.1186/1745-6150-7-32 · Cited by 17 · see citing works
“Furthermore, in a recent complete analysis of relationships between gene fitness profiles (co-fitness) and drug inhibition profiles (co-inhibition) from several hundred chemogenomic screens in yeast [25,26] available at http://fitdb.”
BackgroundParallel Mapping of Antibiotic Resistance Alleles in Escherichia coli
Weiss, S. J., Mansell, T. J., Mortazavi, P., Knight, R. D., & Gill, R. T. (2016) · PLoS ONE · doi:10.1371/journal.pone.0146916 · Cited by 16 · see citing works
Simpkins, S. W., Nelson, J., Deshpande, R., Li, S. C., Piotrowski, J. S., Wilson, E. H., Gebre, A. A., Safizadeh, H., Okamoto, R., Yoshimura, M., et al. (2018) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1006532 · Cited by 15 · see citing works
Chemogenomic profiling in yeast reveals antifungal mode-of-action of polyene macrolactam auroramycin
Wong, J. H., Alfatah, M., Kong, K. W., Hoon, S. S., Yeo, W. L., Ching, K. C., Goh, C. J. H., Zhang, M. M., Lim, Y. H., Wong, F. T., et al. (2019) · PLoS ONE · doi:10.1371/journal.pone.0218189 · Cited by 14 · see citing works
Inference of gene regulatory networks from genome-wide knockout fitness data
Wang, L., Wang, X., Arkin, A. P., & Samoilov, M. S. (2012) · Bioinformatics · doi:10.1093/bioinformatics/bts634 · Cited by 12 · see citing works
“Indeed, it has been shown that this type of data is very useful for the determination of target gene functions (Deutschbauer et al ., 2002, 2011; Hillenmeyer et al. , 2010; Pierce et al ., 2009; Steinmetz et al ., 2002).”
NetwoRx: connecting drugs to networks and phenotypes in Saccharomyces cerevisiae
Fortney, K., Xie, W., Kotlyar, M., Griesman, J., Kotseruba, Y., & Jurišica, I. (2012) · Nucleic Acids Research · doi:10.1093/nar/gks1106 · Cited by 12 · see citing works
“These analyses have included the unsupervised clustering of drug fitness profiles (growth responses) to identify groups of drugs that affect genes in the same way (11,12), and calculating gene co-fitness and using it to predict gene function (13).”
MethodGaponova, A. V., Deneka, A. Y., Beck, T. N., Liu, H., Andrianov, G., Nikonova, A. S., Nicolas, É., Einarson, M. B., Golemis, E. A., & Serebriiskii, I. G. (2016) · Oncotarget · doi:10.18632/oncotarget.13353 · Cited by 12 · see citing works
“To this end, we analyzed the distribution of the 286 selected candidate genes across co-fitness gene clusters that were based on a comprehensive chemogenomic study, which reported the overall profiles of growth of 4,769 homozygous yeast deletion strains [37] in 418 culture conditions, including treatment with FDA-appr…”
InfluentialAlfatah, M., Wong, J. H., Nge, C. E., Kong, K. W., Low, K. N., Leong, C. Y., Crasta, S. C., Madhaiyan, M., Chang, A. M. L., Hoon, S. S., et al. (2019) · Scientific Reports · doi:10.1038/s41598-018-35979-z · Cited by 12 · see citing works
Proposal for a new therapy for drug-resistant malaria using Plasmodium synthetic lethality inference
Lee, S. J., Seo, E., & Cho, Y. H. (2013) · International Journal for Parasitology Drugs and Drug Resistance · doi:10.1016/j.ijpddr.2013.06.001 · Cited by 11 · see citing works
“In this survey, the yeast chemogenomic assays were used to predict its therapeutic potential in malaria (Hillenmeyer et al., 2010).”
MethodSzabó, Z., Balogh, M., Domonkos, Á., Csányi, M., Kaló, P., & Kiss, G. B. (2023) · Theoretical and Applied Genetics · doi:10.1007/s00122-023-04340-y · Cited by 11 · see citing works
“Taking into account the abnormal mutant phenotypes one could conclude, that CYSTM proteins have a more general function than stress tolerance (Lee et al. 1995; Beilharz et al. 2003; Li et al. 2009; Venancio and Aravind 2010; Hillenmeyer et al. 2010; Feng et al. 2011).”
BackgroundComparative Interaction Networks: Bridging Genotype to Phenotype
Beltrão, P., Ryan, C. J., & Krogan, N. J. (2012) · Advances in experimental medicine and biology · doi:10.1007/978-1-4614-3567-9_7 · Cited by 10 · see citing works
“These large-scale chemical-genetic quantitative interactions have been mined to study compound structure– activity relationships [70] and can be integrated with physical [71] and genetic interactions $ w a t e r m a r k - t e x t $ w a t e r m a r k - t e x t $ w a t e r m a r k - t e x t [72] to…”
BackgroundDiethyl phthalate (DEP) perturbs nitrogen metabolism in Saccharomyces cerevisiae
Goh, C. J. H., Cui, L., Wong, J. H., Lewis, J., Goh, M., Kong, K. W., Yang, L. K., Alfatah, M., Kanagasundaram, Y., Hoon, S. S., et al. (2022) · Scientific Reports · doi:10.1038/s41598-022-14284-w · Cited by 10 · see citing works
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Functional genomics in the study of yeast cell polarity: moving in the right direction
Styles, E. B., Youn, J., Ušaj, M. M., & Andrews, B. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2013.0118 · Cited by 9 · see citing works
Gracob: a novel graph-based constant-column biclustering method for mining growth phenotype data
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“This is in agreement with the findings in Hillenmeyer et al. (2010) that co-fitness is a powerful tool to predict cellular functions.”
BackgroundResultLenz, T., & Stühler, K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23105605 · Cited by 9 · see citing works
“The observed similar dose–responses of complex members go in line with the observation in yeast that entire complexes appear to be essential for cell survival (modular essentiality) and that members of the same protein complex respond in a coherent fashion to the same drugs ([62,63]).”
BackgroundRapid Identification of Chemoresistance Mechanisms Using Yeast DNA Mismatch Repair Mutants
Ojini, I., & Gammie, A. E. (2015) · G3 Genes Genomes Genetics · doi:10.1534/g3.115.020560 · Cited by 9 · see citing works
“…involves the use of the yeast fi tness database (FitDB), which is a genome-wide collection of fi tness pro fi les for (cid:1) 4800 single gene yeast deletion strains in response to 400 small molecules and a wide variety of different growth conditions (Hillenmeyer et al. 2010; Hillenmeyer et al. 2008).”
Caldara, M., & Marmiroli, N. (2020) · Microorganisms · doi:10.3390/microorganisms8050742 · Cited by 8 · see citing works
“With this strategy, new drug actions and novel gene functions have already been reported [16,17].”
BackgroundMethodIFIM: a database of integrated fitness information for microbial genes
Wei, W., Ye, Y., Luo, S., Deng, Y., Lin, D. Y., & Guo, F. (2014) · Database · doi:10.1093/database/bau052 · Cited by 8 · see citing works
“…of essential or nonessential genes in some studies; for example, for inferring gene regulatory networks (15), identifying potential virulence genes and drug targets (16–18), revealing different fitness actions in distinct environments (19, 20) and directly detecting conditional essential genes.”
BackgroundZakrzewska, A., Boorsma, A., Beek, A. T., Hageman, J. A., Westerhuis, J. A., Hellingwerf, K. J., Brul, S., Klis, F. M., & Smits, G. J. (2010) · OMICS A Journal of Integrative Biology · doi:10.1089/omi.2010.0049 · Cited by 8 · see citing works
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“lead identification and target classification in yeast (13).”
BackgroundAlfatah, M., Wong, J. H., Kong, K. W., Utama, F., Hoon, S. S., & Arumugam, P. (2019) · Chemosphere · doi:10.1016/j.chemosphere.2019.04.100 · Cited by 8 · see citing works
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“27 , 36 The deletion strains most sensitive to a particular chemical identify its candidate target(s).”
BackgroundBarazandeh, M., Kriti, D., Nislow, C., & Giaever, G. N. (2022) · BMC Genomics · doi:10.1186/s12864-022-08395-x · Cited by 7 · see citing works
“We did not screen nonessential heterozygotes based on the rationale that because the HIP assay requires a drug-induced fitness effect, the reduction in gene-dosage of nonessential genes (which are not required for growth) should not produce a phenotype [20].”
Self-citationSystematic Mapping of Chemical–Genetic Interactions in Saccharomyces cerevisiaePreprint
Suresh, S., Schlecht, U., Xu, W., Bray, W. M., Miranda, M., Davis, R. W., Nislow, C., Giaever, G. N., Lokey, R. S., & St.Onge, R. P. (2016) · Cold Spring Harbor Protocols · doi:10.1101/pdb.top077701 · Cited by 7 · see citing works
Self-citationPredicting drug–target interactions through integrative analysis of chemogenetic assays in yeast
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Evaluation of the lower protein limit in the budding yeast Saccharomyces cerevisiae using TIPI-gTOW
Sasabe, M., Shintani, S., Kintaka, R., Kaizu, K., Makanae, K., & Moriya, H. (2014) · BMC Systems Biology · doi:10.1186/1752-0509-8-2 · Cited by 6 · see citing works
“tions such as specific environmental conditions or in combination with other gene knockouts [13,14].”
BackgroundCallegari, S., Gregory, P. A., Sykes, M. J., Bellon, J., Andrews, S., McKinnon, R. A., & Lopes, M. D. B. (2012) · PLoS Genetics · doi:10.1371/journal.pgen.1002755 · Cited by 6 · see citing works
“However, these assays are prone to a higher incidence of false positive and non-replicable results [29].”
BackgroundMuellner, M. K., Duernberger, G., Ganglberger, F., Kerzendorfer, C., Uras, I. Z., Schönegger, A., Bagienski, K., Colinge, J., & Nijman, S. M. B. (2014) · BMC Bioinformatics · doi:10.1186/1471-2105-15-98 · Cited by 5 · see citing works
“Functional genomic screens that combine two perturbations have been used with great success to uncover such genetic interactions, and also to reveal mechanisms of drug action [1,2].”
BackgroundEckmann, J. B., Enright, A. L., Davies, M., Whelan, E., Myers, K. S., Robinson, M. L., Banta, A. B., Lal, P. B., Coon, J. J., Sato, T. K., et al. (2025) · mSystems · doi:10.1128/msystems.01001-25 · Cited by 4 · see citing works
An algorithm for chemical genomic profiling that minimizes batch effects: bucket evaluations
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Self-citationIntegrative Data-Mining Tools to Link Gene and Function
Yacoubi, B. E., & de Crécy‐Lagard, V. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-721-1_4 · Cited by 4 · see citing works
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Self-citationNutrient Reabsorption Mechanism Adapted to Low Phosphorus in Wild and Cultivated Soybean Varieties
Shen, W., Guo, R., Zhao, Y., Liu, D., Chen, J., Miao, N., Gao, S., Zhang, T., & Shi, L. (2021) · Journal of Plant Growth Regulation · doi:10.1007/s00344-021-10495-z · Cited by 4 · see citing works
Rapid Identification of Chemical Genetic Interactions in Saccharomyces cerevisiae
Dilworth, D., & Nelson, C. J. (2015) · Journal of Visualized Experiments · doi:10.3791/52345 · Cited by 3 · see citing works
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Introduction to Focus Issue: Genetic Interactions
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“Chemical and solvents were purchased from Sigma-Aldrich, except clozapine, which was purchased from Tocris Bioscience (Bio-Techne, Minneapolis, MN, USA).”
MethodA drug similarity network for understanding drug mechanism of action
Karabulut, N. P., Akhmedov, M., & Cokol, M. (2014) · Journal of Bioinformatics and Computational Biology · doi:10.1142/s0219720014410078 · Cited by 2 · see citing works
“…of compounds, we found that drugs having similar chemical structures may have similar e®ects on the yeast cell, which supports the results and hypothesis given by Giaever et al. (2004)5 and Hillenmeyer et al. (2010)7 that cells may show similar responses to drugs having similar structures.”
MethodResultDominance from the perspective of gene–gene and gene–chemical interactions
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“We analyzed the enrichment of Gene Ontology terms (Ashburner et al. 2000) with Ontologizer (Bauer et al. 2008).”
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Genetic Screens for Determination of Mechanism of Action
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From Herbal Remedies to Cutting‐Edge Science
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Interaction between ESCRT-III proteins and the yeast SERINC homolog Tms1
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New hit compounds against Trypanosoma cruzi derived from mining yeast chemogenomic profiling data
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Insights from the reanalysis of high-throughput chemical genomics data for Escherichia coli K-12
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The Molecular Pharmacology of Pateamine A
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Combining drug and gene similarity measures for drug-target elucidation
Sackler, B. (2010)
Bioinformatics Approaches to Biomarker and Drug Discovery in Aging and Disease
Fortney, K. (2012) · TSpace (University of Toronto)
Song, K. (2013) · TSpace (University of Toronto)
Cheung-Ong, K. (2013) · TSpace (University of Toronto)
Mathew, N. D. (2015) · The University of Queensland · doi:10.14264/uql.2015.299
- Authors
- Hillenmeyer, M. E., Ericson, E., Davis, R. W., Nislow, C., Koller, D., & Giaever, G.
- Affiliations
- Stanford University (US)
- University of Toronto (CA)
- Corresponding author
- Koller, Daphne
- Giaever, Guri
- Venue
- Genome Biology
- Published
- 2010-03-12
- Volume
- 11
- Issue
- 3
- Pages
- R30-R30
- ISSN
- 1465-6906 (ISSN-L)
- 1474-760X
- PMC
- PMC2864570
- OpenAlex
- W2121907028
- Cited by
- 112
- References
- 76
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 4 · 2023: 3 · 2022: 9 · 2021: 4 · 2020: 5 · 2019: 3 · 2018: 5 · 2017: 1 · 2016: 8 · 2015: 10 · 2014: 11 · 2013: 13 · 2012: 17
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- TSpace (University of Toronto) (submittedVersion)
- Funders
- National Science Foundation (0345474)
- University of Toronto
- Canadian Institutes of Health Research (81340, (MO)P-81340, 84305)
- National Human Genome Research Institute
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bioinformatics and Genomic Networks
- Keywords
- gene fitness, drug inhibition, CO inhibition, Saccharomyces cerevisiae, gene function prediction, drug target prediction
- MeSH terms
- Copper Transport Proteins, Algorithms, Clozapine, Genes, Fungal, Membrane Proteins, Saccharomyces cerevisiae, Structure-Activity Relationship, Nocodazole, Drug Delivery Systems, Genome, Fungal, Gene Deletion, Molecular Chaperones, Genomics, Drug Resistance, Fungal, Cation Transport Proteins, Saccharomyces cerevisiae Proteins, Systems Biology, Genetic Fitness
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