Large-scale identification and analysis of suppressive drug interactions
Çokol, Murat and Weinstein, Zohar Bat-El and Yılancıoğlu, Kaan and Tasan, Murat and Doak, Allison and Cansever, Dilay and Mutlu, Beste and Li, Siyang and Rodriguez-Esteban, Raul and Akhmedov, Murodzhon and Güvenek, Ayşegül and Çokol, Melike and Çetiner, Selim and Giaever, Guri and Iossifov, Ivan and Nislow, Corey and Shoichet, Brian and Roth, Frederick P. (2014) Large-scale identification and analysis of suppressive drug interactions. Chemistry and Biology, 21 (4). pp. 541-551. ISSN 1074-5521 (Print) 1879-1301 (Online)
Official URL: http://dx.doi.org/10.1016/j.chembiol.2014.02.012
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 drub 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.
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