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The topology of the transcription regulatory network in the yeast, S. cerevisiae

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 نشر من قبل Illes J. Farkas
 تاريخ النشر 2002
  مجال البحث فيزياء علم الأحياء
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MOTIVATION: A central goal of postgenomic biology is the elucidation of the regulatory relationships among all cellular constituents that together comprise the genetic network of a cell or microorganism. Experimental manipulation of gene activity coupled with the assessment of perturbed transcriptome (i. e., global mRNA expression) patterns represents one approach toward this goal, and may provide a backbone into which other measurements can be later integrated. RESULT: We use microarray data on 287 single gene deletion Saccharomyces cerevisiae mutant strains to elucidate generic relationships among perturbed transcriptomes. Their comparison with a method that preferentially recognizes distinct expression subpatterns allows us to pair those transcriptomes that share localized similarities. Analyses of the resulting transcriptome similarity network identify a continuum hierarchy among the deleted genes, and in the frequency of local similarities that establishes the links among their reorganized transcriptomes. We also find a combinatorial utilization of shared expression subpatterns within individual links, with increasing quantitative similarity among those that connect transcriptome states induced by the deletion of functionally related gene products. This suggests a distinct hierarchical and combinatorial organization of the S. cerevisiae transcriptional activity, and may represent a pattern that is generic to the transcriptional organization of all eukaryotic organisms. AVAILABILITY: Detailed analyses of the comparison method and free software are available from the authors and at http://angel.elte.hu/bioinf



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