Integrated Analysis of Multiple Microarray Studies to Identify Novel Gene Signatures in Non-alcoholic Fatty Liver Disease.

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However, the intrinsic molecular mechanisms underlying the pathogenesis of NAFLD have not yet been fully elucidated. Methods: We obtained the gene expression datasets of NAFLD through the Gene Expression Omnibus (GEO) database. Subsequently, robust rank aggregation (RRA) method was used to identify differentially expressed genes (DEGs) between NAFLD patients and controls. Gene functional annotation and PPI network analysis were performed to explore the potential function of the DEGs. Finally, we used a sequencing dataset GSE126848 to validate our results. Results: In this study, GSE48452, GSE66676, GSE72756, GSE63067, GSE89632, and GSE107231 were included, including 125 NAFLD patients and 116 control patients. The RRA integrated analysis determined 96 significant DEGs (50 up-regulated and 46 down-regulated) and the most significant gene aberrantly expressed in NAFLD was ENO3 (P-value = 7.17E-05), followed by CYP7A1 (P-value = 9.04E-05), and P4HA1 (P-value = 1.67E-04). Carboxylic acid metabolic process (GO:0019752; P-value = 1.39E-03) was the most significantly enriched for biological process in GO (gene ontology) analysis. KEGG pathway enrichment analysis showed that steroid hormone biosynthesis (hsa00140; P-value = 6.68E-03) and PPAR signaling pathway (hsa03320; P-value = 9.95E-03) were significantly enriched. Based on the results of the PPI and the results of the RRA, we finally defined the four most critical genes as the hub genes, including ENO3, CYP7A1, P4HA1, and CYP1A1. Conclusions: Our integrated analysis identified novel gene signatures and will contribute to the understanding of comprehensive molecular changes in NAFLD.", "claims": [{"id": "claim-method", "statement": "To minimize the inconsistencies and to integrate the results from several microarray studies, RRA method was adopted to identify robust DEGs, which is an effective tool to integrate multiple arrays outcomes (9, 10).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31551930", "locator": "sections[5] \"RRA Analysis\" paragraph 2", "quote": "To minimize the inconsistencies and to integrate the results from several microarray studies, RRA method was adopted to identify robust DEGs, which is an effective tool to integrate multiple arrays outcomes (9, 10)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets analyzed for this study can be found in the GEO datasets (https://www.ncbi.nlm.nih.gov/gds).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:31551930", "locator": "sections[18] \"Data Availability\" paragraph 2", "quote": "The datasets analyzed for this study can be found in the GEO datasets (https://www.ncbi.nlm.nih.gov/gds)."}], "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:31551930"], "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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