title: Comprehensive reanalysis of transcription factor knockout expression data in Saccharomyces cerevisiae reveals many new targets.
abstract: Transcription factor (TF) perturbation experiments give valuable insights into gene regulation. Genome-scale evidence from microarray measurements may be used to identify regulatory interactions between TFs and targets. Recently, Hu and colleagues published a comprehensive study covering 269 TF knockout mutants for the yeast Saccharomyces cerevisiae. However, the information that can be extracted from this valuable dataset is limited by the method employed to process the microarray data. Here, we present a reanalysis of the original data using improved statistical techniques freely available from the BioConductor project. We identify over 100,000 differentially expressed genes-nine times the total reported by Hu et al. We validate the biological significance of these genes by assessing their functions, the occurrence of upstream TF-binding sites, and the prevalence of protein-protein interactions. The reanalysed dataset outperforms the original across all measures, indicating that we have uncovered a vastly expanded list of relevant targets. In summary, this work presents a high-quality reanalysis that maximizes the information contained in the Hu et al. compendium. The dataset is available from ArrayExpress (accession: E-MTAB-109) and it will be invaluable to any scientist interested in the yeast transcriptional regulatory system.
authors.affiliation: EMBL-European Bioinformatics Institute, Wellcome Trust Genome Campus, Cambridge, UK. juri.reimand@ut.ee
authors.forename: Jüri
authors.initials: J
authors.lastname: Reimand
authors.forename: Juan M
authors.initials: JM
authors.lastname: Vaquerizas
authors.forename: Annabel E
authors.initials: AE
authors.lastname: Todd
authors.forename: Jaak
authors.initials: J
authors.lastname: Vilo
authors.forename: Nicholas M
authors.initials: NM
authors.lastname: Luscombe
mesh_terms: D001665:Binding Sites; D003627:Data Interpretation, Statistical; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D055786:Gene Knockout Techniques; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors
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