Background: A fundamental goal in chemical biology is the elucidation of on- and off-target effectsof drugs and biocides. To this aim chemogenetic screens that quantify drug induced changes incellular fitness, typically taken as changes in composite growth, is commonly applied.Results: Using the model organism Saccharomyces cerevisiae we here report that resolving cellulargrowth dynamics into its individual components, growth lag, growth rate and growth efficiency,increases the predictive power of chemogenetic screens. Both in terms of drug-drug and gene-druginteractions did the individual growth variables capture distinct and only partially overlappingaspects of cell physiology. In fact, the impact on cellular growth dynamics represented functionallydistinct chemical fingerprints.Discussion: Our findings suggest that the resolution and quantification of all facets of growthincreases the informational and interpretational output of chemogenetic screening. Hence, byfacilitating a physiologically more complete analysis of gene-drug and drug-drug interactions thehere reported results may simplify the assignment of mode-of-action to orphan bioactivecompounds.
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