Comprehensive reanalysis of transcription factor knockout expression data in Saccharomyces cerevisiae reveals many new targets.

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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.", "claims": [{"id": "claim-method", "statement": "Differential expression was calculated using a moderated eBayes t-test as implemented in the Limma Bioconductor package (18).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:20385592", "locator": "sections[3] \"Microarray data pre-processing and analysis\" paragraph 2", "quote": "Differential expression was calculated using a moderated eBayes t-test as implemented in the Limma Bioconductor package (18)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data presented here are publicly available from the ArrayExpress database (E-MTAB-109).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:20385592", "locator": "sections[14] \"DISCUSSION\" paragraph 8", "quote": "The data presented here are publicly available from the ArrayExpress database (E-MTAB-109)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "steps": [{"id": "read_published_estimate", "order": 1, "name": "Read the published estimate from the source", "kind": "other", "state": "complete", "blocked_on": null, "description": "The claim, method and evidence span published with the source article.", "duration_hours": null, "parameters": {}, "inputs": ["source:pmid:20385592"], "outputs": ["the published estimate and its evidence"], "instruments": [], "reagents": []}, {"id": "obtain_source_data", "order": 2, "name": "Obtain the source data from the named repository", "kind": "data-preparation", "state": "complete", "blocked_on": null, "description": "The GEO series accession resolves and its sample accessions are listed. 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