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pmid:37474895
Identification of the susceptible genes and mechanism underlying the comorbid presence of coronary artery disease and rheumatoid arthritis: a network modularization analysis.
Siqi Zhang · Qikai Niu · Lin Tong · Sihong Liu · Pengqian Wang · Haiyu Xu · Bing Li · Huamin Zhang
BMC genomics · 2023 doi:10.1186/s12864-023-09519-7
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Experiment
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Complete file
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Here, we aimed to identify the risk genes for the comorbid presence of these two complex diseases using a network modularization approach, to offer insights into clinical therapy and drug development for these diseases.\nMETHOD: The expression profile data of patients CAD with and without RA were obtained from the GEO database (GSE110008). Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits. The Zsummary index, gene significance (GS), and module membership (MM) were utilized to screen the important differentiated modules and hub genes. The GO and KEGG pathway enrichment analysis were applied to analyze potential mechanisms.\nRESULT: Based on the 278 DEGs obtained, 41 modules were identified, of which 17 and 24 modules were positively and negatively correlated with the comorbid occurrence of CAD and RA (CAD&RA), respectively. Thirteen modules with Zsummary < 2 were found to be the underlying modules, which may be related to CAD&RA. With GS ≥ 0.5 and MM ≥ 0.8, 49 hub genes were identified, such as ADO, ABCA11P, POT1, ZNF141, GPATCH8, ATF6 and MIA3, etc. The area under the curve values of the representative seven hub genes under the three models (LR, KNN, SVM) were greater than 0.88. Enrichment analysis revealed that the biological functions of the targeted modules were mainly involved in cAMP-dependent protein kinase activity, demethylase activity, regulation of calcium ion import, positive regulation of tyrosine, phosphorylation of STAT protein, and tissue migration, etc. CONCLUSION: Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases.", "claims": [{"id": "claim-method", "statement": "Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37474895", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Based on the differentially expressed genes (DEGs), weighted gene co-expression network analysis (WGCNA) was used to construct a gene network, detect co-expression modules, and explore their relation to clinical traits."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The raw data of GSE110008 are freely available from GEO database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37474895", "locator": "sections[21] \"notes\" paragraph 1", "quote": "The raw data of GSE110008 are freely available from GEO database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Thirteen characteristic modules and 49 susceptibility hub genes were identified for CAD&RA.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37474895", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Thirteen characteristic modules and 49 susceptibility hub genes were identified, and their corresponding molecular functions may reflect the underlying mechanism of CAD&RA, hence providing insights into the development of clinical therapies against these diseases."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Thirteen characteristic modules and 49 susceptibility hub genes were identified for CAD&RA.", "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:37474895"], "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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