title: Functional analyses of NSF1 in wine yeast using interconnected correlation clustering and molecular analyses.
abstract: Analyzing time-course expression data captured in microarray datasets is a complex undertaking as the vast and complex data space is represented by a relatively low number of samples as compared to thousands of available genes. Here, we developed the Interdependent Correlation Clustering (ICC) method to analyze relationships that exist among genes conditioned on the expression of a specific target gene in microarray data. Based on Correlation Clustering, the ICC method analyzes a large set of correlation values related to gene expression profiles extracted from given microarray datasets. ICC can be applied to any microarray dataset and any target gene. We applied this method to microarray data generated from wine fermentations and selected NSF1, which encodes a C2H2 zinc finger-type transcription factor, as the target gene. The validity of the method was verified by accurate identifications of the previously known functional roles of NSF1. In addition, we identified and verified potential new functions for this gene; specifically, NSF1 is a negative regulator for the expression of sulfur metabolism genes, the nuclear localization of Nsf1 protein (Nsf1p) is controlled in a sulfur-dependent manner, and the transcription of NSF1 is regulated by Met4p, an important transcriptional activator of sulfur metabolism genes. The inter-disciplinary approach adopted here highlighted the accuracy and relevancy of the ICC method in mining for novel gene functions using complex microarray datasets with a limited number of samples.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada ; School of Computer Science, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Kyrylo
authors.initials: K
authors.lastname: Bessonov
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Walkey
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Shelp
authors.forename: Hennie J J
authors.initials: HJ
authors.lastname: van Vuuren
authors.forename: David
authors.initials: D
authors.lastname: Chiu
authors.forename: George
authors.initials: G
authors.lastname: van der Merwe
mesh_terms: D050976:Basic-Leucine Zipper Transcription Factors / Q000378:metabolism; D005285:Fermentation; D015966:Gene Expression Regulation, Fungal; D042541:Intracellular Space / Q000378:metabolism; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism*; D013455:Sulfur / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic; D014920:Wine / Q000382:microbiology*
chemical_list: D050976:Basic-Leucine Zipper Transcription Factors; C073675:MET4 protein, S cerevisiae; C000588770:NSF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; D013455:Sulfur