Chemogenetic fingerprinting by analysis of cellular growth dynamics.

BMC Chemical Biology
J WarringerA Blomberg

Abstract

A fundamental goal in chemical biology is the elucidation of on- and off-target effects of drugs and biocides. To this aim chemogenetic screens that quantify drug induced changes in cellular fitness, typically taken as changes in composite growth, is commonly applied. Using the model organism Saccharomyces cerevisiae we here report that resolving cellular growth 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-drug interactions did the individual growth variables capture distinct and only partially overlapping aspects of cell physiology. In fact, the impact on cellular growth dynamics represented functionally distinct chemical fingerprints. Our findings suggest that the resolution and quantification of all facets of growth increases the informational and interpretational output of chemogenetic screening. Hence, by facilitating a physiologically more complete analysis of gene-drug and drug-drug interactions the here reported results may simplify the assignment of mode-of-action to orphan bioactive compounds.

References

Nov 1, 1995·Neural Computation·F Mulier, V Cherkassky
Nov 15, 1996·The Journal of Biological Chemistry·J R MurguíaR Serrano
Jul 26, 2002·Nature·Guri GiaeverMark Johnston
May 31, 2003·Journal of Biology·Roy Kishony, Stanislas Leibler
Dec 17, 2003·Proceedings of the National Academy of Sciences of the United States of America·Jonas WarringerAnders Blomberg
Jan 14, 2004·Proceedings of the National Academy of Sciences of the United States of America·Guri GiaeverRonald W Davis
May 28, 2005·Bioinformatics·Patrick FlahertyAdam P Arkin
Jun 2, 2006·Molecular Systems Biology·James A BrownJ Martin Brown
Jul 19, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marie OsterbergGunnar von Heijne
Mar 3, 2007·Molecular Systems Biology·Joseph LehárCurtis T Keith
Apr 15, 2008·Nature Genetics·Alexander DeLunaRoy Kishony
Apr 19, 2008·Science·Maureen E HillenmeyerGuri Giaever

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Citations

Feb 18, 2011·The ISME Journal·Daniel SherSallie W Chisholm
Feb 10, 2012·Molecular Biology and Evolution·Enikö ZörgöJonas Warringer
Aug 5, 2011·BMC Bioinformatics·Tahir MehmoodLars Snipen
Feb 2, 2013·BMC Genomics·Gianni LitiConrad A Nieduszynski
Aug 10, 2010·BMC Chemical Biology·Md AlamgirAshkan Golshani
Jun 24, 2011·PLoS Genetics·Jonas WarringerAnders Blomberg
Apr 5, 2013·PLoS Genetics·Enikö ZörgöJonas Warringer
Nov 26, 2010·Current Opinion in Biotechnology·Anders Blomberg
Jan 26, 2011·Molecular Ecology·Francisco A CubillosGianni Liti
Oct 29, 2014·Molecular Biology and Evolution·Sebastian IbstedtJonas Warringer
Jun 24, 2016·BMC Bioinformatics·Luciano Fernandez-RicaudAnders Blomberg
Nov 3, 2016·Nature Communications·Johan HallinGianni Liti
Mar 28, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yannick NeyClaus Jacob
Nov 20, 2016·G3 : Genes - Genomes - Genetics·Thurston HerricksJohn D Aitchison
Aug 3, 2017·Cold Spring Harbor Protocols·Gianni LitiAnders Blomberg
Jan 30, 2014·G3 : Genes - Genomes - Genetics·Aatish BhatiaHimanshu Sinha
Jul 14, 2018·Nature Communications·Shou-Fu DuanFeng-Yan Bai
Jul 3, 2016·G3 : Genes - Genomes - Genetics·Martin ZackrissonAnders Blomberg
Aug 3, 2010·Eukaryotic Cell·Lars-Göran OttossonJonas Warringer
Dec 6, 2019·MedChemComm·Xiao Tan, Samuel G Awuah

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Methods Mentioned

BETA
gene knockouts
gene knockout

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