2014
DOI: 10.1016/j.cell.2014.02.054
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Large-Scale Genetic Perturbations Reveal Regulatory Networks and an Abundance of Gene-Specific Repressors

Abstract: To understand regulatory systems, it would be useful to uniformly determine how different components contribute to the expression of all other genes. We therefore monitored mRNA expression genome-wide, for individual deletions of one-quarter of yeast genes, focusing on (putative) regulators. The resulting genetic perturbation signatures reflect many different properties. These include the architecture of protein complexes and pathways, identification of expression changes compatible with viability, and the var… Show more

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Cited by 286 publications
(500 citation statements)
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“…Currently, the TFs that regulate a process of interest are typically discovered by large-scale mutant screens, and TF-target relations are mapped in big-science projects that do not focus on TFs with specific biological functions (Harbison et al 2004;Hu et al 2007;Kemmeren et al 2014). Our approach brings TF discovery and mapping together through focused, iterative network construction and analysis.…”
Section: Discussionmentioning
confidence: 99%
“…Currently, the TFs that regulate a process of interest are typically discovered by large-scale mutant screens, and TF-target relations are mapped in big-science projects that do not focus on TFs with specific biological functions (Harbison et al 2004;Hu et al 2007;Kemmeren et al 2014). Our approach brings TF discovery and mapping together through focused, iterative network construction and analysis.…”
Section: Discussionmentioning
confidence: 99%
“…With limited knowledge of CRCs in most cell types, attempts to map the control of gene expression programs have thus far been dominated by efforts to integrate global information regarding gene-gene, protein-protein, gene-protein, and regulatory element interactions nested in these networks (Lefebvre et al 2010;Gerstein et al 2012;Neph et al 2012;Yosef et al 2013;Kemmeren et al 2014;Rolland et al 2014). These global studies have provided foundational resources and important insights into basic principles governing transcriptional regulatory networks.…”
Section: [Supplemental Materials Is Available For This Article]mentioning
confidence: 99%
“…We consider large-scale gene deletion experiments in yeast (Saccharomyces cerevisiae) (40). Genome-wide mRNA expression levels are measured for 6,170 genes: 160 observational data points from wild-type individuals and 1,479 interventional data arising from single gene deletions (1,479 perturbation/deletion experiments where a single gene has been deleted from a strain).…”
Section: Validation: Gene Perturbation Experimentsmentioning
confidence: 99%