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Extracting the hidden features in saline osmotic tolerance in Saccharomyces cerevisiae from DNA microarray data using the self-organizing map: biosynthesis of amino acids.

Pandey G, Yoshikawa K, Hirasawa T, Nagahisa K, Katakura Y, Furusawa C, Shimizu H, Shioya S

Department of Biotechnology, Graduate School of Engineering, Osaka University, 2-1 Yamadaoka, Suita, Osaka, 565-0871, Japan.

During saline stress, Saccharomyces cerevisiae changes its metabolic fluxes through the direct accumulation of metabolites such as glycerol and trehalose, which in turn provide tolerance to the cell against stress. Previous research shows that the various controls at both transcriptional and translational levels decide the phenomenon of stress, but details about such transition is still not very clear. This paper attempts to extract some hidden features through the information extraction approach from DNA microarray data during transition to osmotic tolerance, which are expected to be important in directing to the tolerance stage upon encountering osmotic stress in yeast. Time course of DNA microarray data during osmotic tolerance was analyzed by computational approach 'self-organizing map (SOM) extended with hierarchical clustering'. Since eukaryotic gene expression is governed by short regulatory sequences found upstream in promoter regions, therefore clusters containing the similar profiles obtained by SOM were further analyzed for overrepresentation of known regulatory binding sites in promoter region. It was found that apart from known and expected 'STRE' during osmotic stress, the 'GCN4' binding site is also found to be significant. Hence, it was suggested that the process of osmotic tolerance proceeds through a stage of amino acid starvation. The intracellular amino acids pool also found to be depleted during transition and restoration is faster in brewing strain than laboratory strain. Experiments involving supplementation of amino acids helps in reducing the lag time for recovery, which was found to be similar to that of brewing strain.

Published 4 June 2007 in Appl Microbiol Biotechnol, 75(2): 415-26.
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Promoter and CpG Island Microarrays (Nuts & Bolts series)