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

TL;DR

This study maps the transcription regulatory network in yeast by analyzing gene deletion mutants and transcriptome similarities, revealing a hierarchical and combinatorial organization of gene regulation.

Contribution

It introduces a novel network analysis method based on transcriptome similarity, uncovering hierarchical and combinatorial patterns in yeast gene regulation.

Findings

Identified a continuum hierarchy among deleted genes.

Revealed a combinatorial utilization of shared expression subpatterns.

Suggested a hierarchical and combinatorial organization of transcriptional activity.

Abstract

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