Large-Scale Identification and Analysis of Suppressive Drug Interactions

Cokol, M., Weinstein, Z. B., Yilancioglu, K., Tasan, M., Doak, A., Cansever, D., Mutlu, B., Li, S., Rodriguez-Esteban, R., Akhmedov, M., Guvenek, A., Cokol, M., Cetiner, S., Giaever, G., Iossifov, I., Nislow, C., Shoichet, B., Roth, F. P. (April 2014) Large-Scale Identification and Analysis of Suppressive Drug Interactions. Chemistry & Biology, 21 (4). pp. 541-551. ISSN 1074-5521

URL: http://www.ncbi.nlm.nih.gov/pubmed/24704506
DOI: 10.1016/j.chembiol.2014.02.012

Abstract

One drug may suppress the effects of another. Although knowledge of drug suppression is vital to avoid efficacy-reducing drug interactions or discover countermeasures for chemical toxins, drug-drug suppression relationships have not been systematically mapped. Here, we analyze the growth response of Saccharomyces cerevisiae to anti-fungal compound ("drug") pairs. Among 440 ordered drug pairs, we identified 94 suppressive drug interactions. Using only pairs not selected on the basis of their suppression behavior, we provide an estimate of the prevalence of suppressive interactions between anti-fungal compounds as 17%. Analysis of the drug suppression network suggested that Bromopyruvate is a frequently suppressive drug and Staurosporine is a frequently suppressed drug. We investigated potential explanations for suppressive drug interactions, including chemogenomic analysis, coaggregation, and pH effects, allowing us to explain the interaction tendencies of Bromopyruvate.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > computers > computer software
bioinformatics > genomics and proteomics > databases > databases
bioinformatics > genomics and proteomics > datasets
diseases & disorders > cancer > drugs and therapies
CSHL Authors:
Communities: CSHL labs > Iossifov lab
Depositing User: Matt Covey
Date: 2 April 2014
Date Deposited: 11 Apr 2014 20:16
Last Modified: 07 Apr 2015 16:20
PMCID: PMC4281482
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29732

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