title: Comparative analysis of transcriptome and fitness profiles reveals general and condition-specific cellular functions involved in adaptation to environmental change in Saccharomyces cerevisiae.
abstract: The transcriptional responses of yeast cells to a wide variety of stress conditions have been studied extensively. In addition, deletion mutant collections have been widely used to measure the combined effect of gene loss and stress on growth (fitness). Here we present a comparative analysis of 1,095 publicly available transcription and genome-wide fitness profiles in yeast, from different laboratories and experimental platforms. We analyzed these data, using T-profiler, to describe the correlation in behavior of a priori defined functional groups. Two-mode clustering analysis of the fitness T-profiles revealed that functional groups involved in regulating ribosome biogenesis and translation offer general stress resistance. These groups are closely related to growth rate and nutrient availability. General stress sensitivity was found in deletion mutant groups functioning in intracellular vesicular transport, actin cytoskeleton organization, and cell polarity, indicating that they play an key role in maintaining yeast adaptability. Analysis of the phenotypic and transcriptional variability of our a priori defined functional groups showed that the quantitative effect on fitness of both resistant and sensitive groups is highly condition-dependent. Finally, we discuss the implications of our results for combinatorial drug design.
authors.affiliation: Molecular Biology and Microbial Food Safety, Swammerdam Institute for Life Sciences, Netherlands Institute for Systems Biology, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Anna
authors.initials: A
authors.lastname: Zakrzewska
authors.forename: Andre
authors.initials: A
authors.lastname: Boorsma
authors.forename: Alex Ter
authors.initials: AT
authors.lastname: Beek
authors.forename: Jos A
authors.initials: JA
authors.lastname: Hageman
authors.forename: Johan A
authors.initials: JA
authors.lastname: Westerhuis
authors.forename: Klaas J
authors.initials: KJ
authors.lastname: Hellingwerf
authors.forename: Stanley
authors.initials: S
authors.lastname: Brul
authors.forename: Frans M
authors.initials: FM
authors.lastname: Klis
authors.forename: Gertien J
authors.initials: GJ
authors.lastname: Smits
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D000935:Antifungal Agents; D016000:Cluster Analysis; D030541:Databases, Genetic; D015195:Drug Design; D004777:Environment; D020869:Gene Expression Profiling; D056084:Genetic Fitness; D016681:Genome, Fungal; D055106:Genome-Wide Association Study; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000502:physiology*
chemical_list: D000935:Antifungal Agents