Integrated Bioinformatics Identifies NLRP3 Inflammasome Hub Genes and Therapeutic Targets in Schizophrenia.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41356282", "kind": "science-record", "revision": 4, "content_hash": "sha256:7370bd74b282e411195da878de4586b02f73020ef5ccb71605b6a6893ff54b8b", "created_at": "2026-11-01T20:31:22Z", "updated_at": "2026-11-01T22:57:34Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Integrated Bioinformatics Identifies NLRP3 Inflammasome Hub Genes and Therapeutic Targets in Schizophrenia.", "doi": "10.2147/NDT.S555802", "pmid": "41356282", "authors": ["Jiawei Ma", "Yongchun Cui", "Xinying Li", "Ruiyuan Liu", "Jinhui Wang", "Mengdi Liu", "Linping Kong", "Yan Ren"], "journal": "Neuropsychiatric disease and treatment", "year": 2025, "abstract": "Background: The pathogenesis of schizophrenia (SZ) remains incompletely understood; although neuroinflammation and the NLRP3 inflammasome have been implicated, the key regulatory genes involved are still unidentified.\nObjective: To investigate the association between SZ and NLRP3 inflammasome-related genes, and to screen for hub genes as potential biomarkers and therapeutic targets.\nMethods: We analyzed the GEO dataset GSE27383, comprising 43 SZ patients and 29 controls, and identified 1,672 differentially expressed genes (DEGs). NLRP3-related genes were obtained from GeneCards, and weighted gene co-expression network analysis (WGCNA) highlighted the green, yellow, and red modules. The intersection of DEGs, NLRP3-related genes, and module genes was further refined using LASSO and Random Forest algorithms. Immune cell infiltration was profiled with CIBERSORT, and the diagnostic utility of candidate genes was evaluated using ROC curves. Molecular docking was performed to predict compound binding, and hub gene expression was validated in an independent cohort of 20 SZ patients and 20 controls using RT-qPCR on PBMCs.\nResults: Five hub genes-HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS-were significantly down-regulated in SZ (P < 0.05). The combined ROC-AUC reached 0.883. Molecular docking revealed strong binding affinities of ellagic acid to FLNA (-4.70 kcal mol- 1), and of hydralazine to HSPA8 (-4.27), TRAF2 (-4.84), and SCAP (-4.98). Differential expression was confirmed in PBMCs. Additionally, SZ patients exhibited increased naive B cells and neutrophils, along with reduced resting NK cells and M2 macrophages.\nConclusion: Five genes (HSPA8, SCAP, FLNA, TRAF2, PINK1-AS) were identified as potential novel biomarkers and therapeutic targets for SZ, providing a theoretical foundation for elucidating disease mechanisms and advancing precision medicine in SZ.", "claims": [{"id": "claim-method", "statement": "The Limma package in R software was used to screen differentially expressed genes (DEGs) based on p < 0.05 and |log FC| > 0.1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41356282", "locator": "sections[5] \"Differential Expression Analysis\" paragraph 2", "quote": "The Limma package in R software was used to screen differentially expressed genes (DEGs) based on p < 0.05 and |log FC| > 0.1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analysed during this study are included in this published article. The public datasets analysed are available in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/). Any additional raw data that are not publicly available can be obtained upon reasonable request to the two Corresponding Authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41356282", "locator": "sections[33] \"Data Sharing Statement\" paragraph 2", "quote": "All data generated or analysed during this study are included in this published article. The public datasets analysed are available in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/). Any additional raw data that are not publicly available can be obtained upon reasonable request to the two Corresponding Authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Five hub genes—HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS—were significantly down-regulated in SZ (P < 0.05).", "kind": "quantitative", "target": {"value": 0.05, "unit": "p-value", "tolerance": null, "source": "Five hub genes—HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS—were significantly down-regulated in SZ (P < 0.05)."}, "evidence": [{"asset": "source:pmid:41356282", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Five hub genes—HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS—were significantly down-regulated in SZ (P < 0.05)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Five hub genes—HSPA8, SCAP, FLNA, TRAF2, and PINK1-AS—were significantly down-regulated in SZ (P < 0.05).", "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:41356282"], "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:GSE27383"], "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:GSE27383"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41356282", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/NDT.S555802", "sha256": "sha256:4af087b9d7c9b34260a0fb03019c54f616b016d0b73113a0874f55386cbb82b3", "bytes": 43728, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.2147/NDT.S555802", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12679867", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE27383", "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=GSE27383", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE27383", "version": null, "note": "All data generated or analysed during this study are included in this published article. The public datasets analysed are available in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/). Any additional raw data that are not publicly available can be obtained upon reasonable request to the two Corresponding Authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analysed during this study are included in this published article. The public datasets analysed are available in the NCBI Gene Expression Omnibus (GEO) repository (https://www.ncbi.nlm.nih.gov/geo/). 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A run that reproduces the effect is judged against this threshold."}], "gaps": []}, "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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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