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pmid:33032623
Gene correlation network analysis to identify regulatory factors in sepsis.
Zhongheng Zhang · Lin Chen · Ping Xu · Lifeng Xing · Yucai Hong · Pengpeng Chen
Journal of translational medicine · 2020 doi:10.1186/s12967-020-02561-z
Paper
complete
Experiment
complete
Data
partial
Analysis
partial
Execution
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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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Complete file
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The study aimed to identify master regulators of mortality-related modules, providing potential therapeutic target for further translational experiments.\nMETHODS: The dataset GSE65682 from the Gene Expression Omnibus (GEO) database was utilized for bioinformatic analysis. Consensus weighted gene co-expression netwoek analysis (WGCNA) was performed to identify modules of sepsis. The module most significantly associated with mortality were further analyzed for the identification of master regulators of transcription factors and miRNA.\nRESULTS: A total number of 682 subjects with various causes of sepsis were included for consensus WGCNA analysis, which identified 27 modules. The network was well preserved among different causes of sepsis. Two modules designated as black and light yellow module were found to be associated with mortality outcome. Key regulators of the black and light yellow modules were the transcription factor CEBPB (normalized enrichment score = 5.53) and ETV6 (NES = 6), respectively. The top 5 miRNA regulated the most number of genes were hsa-miR-335-5p (n = 59), hsa-miR-26b-5p (n = 57), hsa-miR-16-5p (n = 44), hsa-miR-17-5p (n = 42), and hsa-miR-124-3p (n = 38). Clustering analysis in 2-dimension space derived from manifold learning identified two subclasses of sepsis, which showed significant association with survival in Cox proportional hazard model (p = 0.018).\nCONCLUSIONS: The present study showed that the black and light-yellow modules were significantly associated with mortality outcome. Master regulators of the module included transcription factor CEBPB and ETV6. miRNA-target interactions identified significantly enriched miRNA.", "claims": [{"id": "claim-method", "statement": "The association of each module with the survival outcome was determined by using Cox proportional model.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33032623", "locator": "sections[9] \"Survival analysis\" paragraph 2", "quote": "The association of each module with the survival outcome was determined by using Cox proportional model."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Data were available on request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33032623", "locator": "sections[28] \"notes\" paragraph 1", "quote": "Data were available on request."}], "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:33032623"], "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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