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dc.contributor.authorKuo, Dwight
dc.contributor.authorTan, Kai
dc.contributor.authorZinman, Guy
dc.contributor.authorRavasi, Timothy
dc.contributor.authorBar-Joseph, Ziv
dc.contributor.authorIdeker, Trey
dc.date.accessioned2014-11-11T14:30:37Z
dc.date.available2014-11-11T14:30:37Z
dc.date.issued2010-08-24
dc.identifier.citationKuo D, Tan K, Zinman G, Ravasi T, Bar-Joseph Z, et al. (2010) Evolutionary divergence in the fungal response to fluconazole revealed by soft clustering. Genome Biology 11: R77. doi:10.1186/gb-2010-11-7-r77.
dc.identifier.issn1465-6906
dc.identifier.pmid20653936
dc.identifier.doi10.1186/gb-2010-11-7-r77
dc.identifier.urihttp://hdl.handle.net/10754/334580
dc.description.abstractBackground: Fungal infections are an emerging health risk, especially those involving yeast that are resistant to antifungal agents. To understand the range of mechanisms by which yeasts can respond to anti-fungals, we compared gene expression patterns across three evolutionarily distant species - Saccharomyces cerevisiae, Candida glabrata and Kluyveromyces lactis - over time following fluconazole exposure. Results: Conserved and diverged expression patterns were identified using a novel soft clustering algorithm that concurrently clusters data from all species while incorporating sequence orthology. The analysis suggests complementary strategies for coping with ergosterol depletion by azoles - Saccharomyces imports exogenous ergosterol, Candida exports fluconazole, while Kluyveromyces does neither, leading to extreme sensitivity. In support of this hypothesis we find that only Saccharomyces becomes more azole resistant in ergosterol-supplemented media; that this depends on sterol importers Aus1 and Pdr11; and that transgenic expression of sterol importers in Kluyveromyces alleviates its drug sensitivity. Conclusions: We have compared the dynamic transcriptional responses of three diverse yeast species to fluconazole treatment using a novel clustering algorithm. This approach revealed significant divergence among regulatory programs associated with fluconazole sensitivity. In future, such approaches might be used to survey a wider range of species, drug concentrations and stimuli to reveal conserved and divergent molecular response pathways.
dc.language.isoen
dc.publisherSpringer Nature
dc.rights.urihttp://creativecommons.org/licenses/by/2.0/
dc.titleEvolutionary divergence in the fungal response to fluconazole revealed by soft clustering
dc.typeArticle
dc.contributor.departmentBiological and Environmental Sciences and Engineering (BESE) Division
dc.contributor.departmentBioscience Program
dc.contributor.departmentComputational Bioscience Research Center (CBRC)
dc.contributor.departmentIntegrative Systems Biology Lab
dc.contributor.departmentRed Sea Research Center (RSRC)
dc.identifier.journalGenome Biology
dc.identifier.pmcidPMC2926788
dc.eprint.versionPublisher's Version/PDF
dc.contributor.institutionDepartments of Bioengineering and Medicine, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA
dc.contributor.institutionDepartments of Internal Medicine and Biomedical Engineering, University of Iowa, 200 Hawkins Drive, Iowa City, IA 52242, USA
dc.contributor.institutionDepartment of Computer Science, Carnegie Mellon University, 500 Forbes Avenue, Pittsburgh, PA 15213, USA
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)
kaust.personRavasi, Timothy
refterms.dateFOA2018-06-14T04:39:14Z
dc.date.published-online2010-08-24
dc.date.published-print2010


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