Parsons AB~Boone C, 2006

Pubmed ID 16901791
Title Exploring the mode-of-action of bioactive compounds by chemical-genetic profiling in yeast.
Authors Ainslie B Parsons, Andres Lopez, Inmar E Givoni, David E Williams, Christopher A Gray, Justin Porter, Gordon Chua, Richelle Sopko, Renee L Brost, Cheuk-Hei Ho, Jiyi Wang, Troy Ketela, Charles Brenner, Julie A Brill, G Esteban Fernandez, Todd C Lorenz, Gregory S Payne, Satoru Ishihara, Yoshikazu Ohya, Brenda Andrews, Timothy R Hughes, Brendan J Frey, Todd R Graham, Raymond J Andersen, Charles Boone
Abstract Discovering target and off-target effects of specific compounds is critical to drug discovery and development. We generated a compendium of "chemical-genetic interaction" profiles by testing the collection of viable yeast haploid deletion mutants for hypersensitivity to 82 compounds and natural product extracts. To cluster compounds with a similar mode-of-action and to reveal insights into the cellular pathways and proteins affected, we applied both a hierarchical clustering and a factorgram method, which allows a gene or compound to be associated with more than one group. In particular, tamoxifen, a breast cancer therapeutic, was found to disrupt calcium homeostasis and phosphatidylserine (PS) was recognized as a target for papuamide B, a cytotoxic lipopeptide with anti-HIV activity. Further, the profile of crude extracts resembled that of its constituent purified natural product, enabling detailed classification of extract activity prior to purification. This compendium should serve as a valuable key for interpreting cellular effects of novel compounds with similar activities.
Citation Cell 2006; 126:611-25

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) abietic acid [0.33 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) (+)-coniine [5% v/v] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) (+)-usnic acid [61 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) l-Menthol [480 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) camptothecin [30 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) 1,10-Phenanthroline hydrate [0.02 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) 2-hydrazinoethanol [5% v/v] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) afimoxifene [36.1 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) actinomycin D [37 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) Agelasine E [0.03 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) ALAMETHICIN [59.3 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) amantadine hydrochloride [5.9 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) Amiodarone hydrochloride [150 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) amphotericin B [0.76 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) (-)-anisomycin [3.8 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) (+)-artemisinin [88.5 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) Basiliskamide [0.26 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) benomyl [0.12 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) brefeldin A [0.36 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) caffeine [3.1 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) Calcimycin [191 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) caspofungin [7 nM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) cerulenin [1.6 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) chlorpromazine hydrochloride [28.2 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) cisplatin [0.17 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) clomiphene citrate [4.9 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) clotrimazole [0.4 nM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) cyclopiazonic acid [0.4 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) cytochalasin a [21 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) desipramine hydrochloride [231 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) doxycycline hyclate [1.12 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) dyclonine hydrochloride [55.2 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) EMETINE DIHYDROCHLORIDE [1.25 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) emodin [0.4 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 00-132 [32 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 00-192 [15 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 00-243 [10 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 00-303C [29 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 00-89 [5 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 6592 [130 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) extract 95-57 [30 ug/ml] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) fenpropimorph [0.00001% (v/v)] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) tacrolimus (anhydrous) [9 nM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) fluconazole [0.03 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) geldanamycin [36 nM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) haloperidol [0.1 mM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) Harmine Hydrochloride [241.2 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) pibenzimol [93.7 uM] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) hydrogen peroxide [0.4%(v/v)] hap a 4,111 Quantitative
Parsons AB~Boone C, 2006 growth (relative abundance in pooled culture) hydroxyurea [20 mM] hap a 4,111 Quantitative
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Curation history

Data

May 29, 2015 Ready to load.
July 23, 2015 Loaded.

Tested strains

May 29, 2015 Ready to load.
July 23, 2015 Loaded.