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pmid:38510807
Exploring hub genes and crucial pathways linked to oxidative stress in bipolar disorder depressive episodes through bioinformatics analysis.
Shasha Wu · Haiyang Hu · Yilin Li · Yan Ren
Frontiers in psychiatry · 2024 doi:10.3389/fpsyt.2024.1323527
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Complete file
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There is a substantial body of literature linking psychiatric disorders, including BD, to oxidative stress (OS). Consequently, this study aims to assess the relationship between BD and OS by identifying key hub genes implicated in OS pathways.\nMethods: We acquired gene microarray data from GSE5392 through the Gene Expression Omnibus (GEO). Our approach encompassed differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Protein-Protein Interaction (PPI) Network analysis to pinpoint hub genes associated with BD. Subsequently, we utilized Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) to identify hub genes relevant to OS. To evaluate the diagnostic accuracy of these hub genes, we performed receiver operating characteristic curve (ROC) analysis on both GSE5388 and GSE5389 datasets. Furthermore, we conducted a study involving ten BD patients and ten healthy controls (HCs) who met the special criteria, assessing the expression levels of these hub genes in their peripheral blood mononuclear cells (PBMCs).\nResults: We identified 411 down-regulated genes and 69 up-regulated genes for further scrutiny. Through WGCNA, we obtained 22 co-expression modules, with the sienna3 module displaying the strongest association with BD. By integrating differential analysis with genes linked to OS, we identified 44 common genes. Subsequent PPI Network and WGCNA analyses confirmed three hub genes as potential biomarkers for BD. Functional enrichment pathway analysis revealed their involvement in neuronal signal transduction, oxidative phosphorylation, and metabolic obstacle pathways. Using the Cytoscape plugin \"ClueGo assay,\" we determined that a majority of these targets regulate neuronal synaptic plasticity. ROC curve analysis underscored the excellent diagnostic value of these three hub genes. Quantitative reverse transcription-PCR (RT-qPCR) results indicated significant changes in the expression of these hub genes in the PBMCs of BD patients compared to HCs.\nConclusion: We identified three hub genes (TAC1, MAP2K1, and MAP2K4) in BD associated with OS, potentially influencing the diagnosis and treatment of BD. Based on the GEO database, our study provides novel insights into the relationship between BD and OS, offering promising therapeutic targets.", "claims": [{"id": "claim-method", "statement": "In pursuit of early disease detection and diagnosis, the generalized linear regression analytic model of logistic regression emerged as a valuable tool.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38510807", "locator": "sections[10] \"Screening and validation of hub genes\" paragraph 2", "quote": "In pursuit of early disease detection and diagnosis, the generalized linear regression analytic model of logistic regression emerged as a valuable tool."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found here: GSE5392: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5392. GSE5388: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5388. 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GSE5389: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5389."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The hub-gene diagnostic model achieved an AUC of 0.799 in GSE5392, with AUCs of 0.79 and 0.82 in GSE5388 and GSE5389, respectively.", "kind": "quantitative", "target": {"value": 0.799, "unit": "auc", "tolerance": null, "source": "The results demonstrated that the hub genes-based predictive model had effective diagnostic performance, with an AUC of 0.799 ( Figure 10A )."}, "evidence": [{"asset": "source:pmid:38510807", "locator": "sections[20] \"Validation of a diagnostic model\" paragraph 2", "quote": "The results demonstrated that the hub genes-based predictive model had effective diagnostic performance, with an AUC of 0.799 ( Figure 10A )."}, {"asset": "source:pmid:38510807", "locator": "sections[20] \"Validation of a diagnostic model\" paragraph 2", "quote": "With AUCs 0.79 and 0.82, respectively, the models in GSE5388 and GSE5389 had reasonably high AUCs ( Figures 10B, C )."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The hub-gene diagnostic model achieved an AUC of 0.799 in GSE5392, with AUCs of 0.79 and 0.82 in GSE5388 and GSE5389, respectively.", "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:38510807"], "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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE5388"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "complete", "blocked_on": null, "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE5388"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38510807", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fpsyt.2024.1323527", "sha256": "sha256:b9ba05798ae5de0579784f4c6bf187b1d1688c2c85c0dc8e2087aa4b2ebf4b72", "bytes": 41022, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fpsyt.2024.1323527", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10950934", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE5388", "role": "raw", "format": "geo-series", "media_type": "application/vnd.ncbi.geo-series+json", "uri": "https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE5388", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE5388", "version": null, "note": "Publicly available datasets were analyzed in this study. 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No tolerance is published because the paper states none."}], "gaps": ["method.reader_differs_from_extractor"]}, "capability": {"state": "complete", "requirements": [{"capability_id": "capability:computational_analysis", "label": "Computational analysis platform", "assay_families": ["meta_analysis", "machine_learning", "survival_analysis", "statistical_regression", "pca", "molecular_docking", "network_analysis", "differential_expression", "gwas"], "availability_state": "owned", "tier_unlocked": "R1", "candidate": "Automated Assays Laravel application and simulated adapters"}], "gaps": []}, "readiness": {"state": "complete", "tier": "R1", "blocking_axis": "none", "blocked_on": "nothing:replicable_now", "axes": {"method": {"tier": "R1", "expressible": true, "required_operations": ["glm_logit_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: logistic."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Methods: We acquired gene microarray data from GSE5392 through the Gene Expressio"], "order_basis": "paper_text_order:557", "id": "assay:1"}, {"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["nes. Quantitative reverse transcription-PCR (RT-qPCR) results indicated significant changes in th", ". Quantitative reverse transcription-PCR (RT-qPCR) results indicated significant changes in th"], "order_basis": "paper_text_order:2226", "id": "assay:2"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["In pursuit of early disease detection and diagnosis, the generalized linear regression analytic model of logistic regression emerged as a valuable tool."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}