Molecular subtype and RNA transcriptomics validation for rheumatoid arthritis characterized by fatty acid metabolism-related immune landscape.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40777023", "kind": "science-record", "revision": 3, "content_hash": "sha256:32594cbfeaaf62c69bfe6f5c751a1edfa0829362448f97c07ad078be98e7a522", "created_at": "2026-11-01T20:30:52Z", "updated_at": "2026-11-01T22:14:30Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Molecular subtype and RNA transcriptomics validation for rheumatoid arthritis characterized by fatty acid metabolism-related immune landscape.", "doi": "10.3389/fimmu.2025.1611000", "pmid": "40777023", "authors": ["Peng Zhang", "Yu Wen", "Xin Li", "Yihong Yang", "Youbang Liang", "Chenguang Zhan", "Liyan Mei", "Haifang Du", "Xiumin Chen", "Maojie Wang", "Runyue Huang", "Xiaodong Wu"], "journal": "Frontiers in immunology", "year": 2025, "abstract": "Background: Rheumatoid arthritis (RA) is a rheumatic disease charactered by severe bone destruction. Evidence suggests that fatty acid metabolism (FAM)-related proteins can regulate inflammation of synoviocytes in RA. However, the fundamental roles of FAM regulators in RA remain to be elucidated.\nMethods: We selected the GSE93272 dataset sourced from the Gene Expression Omnibus (GEO) for the classification of FAM-associated molecular subtypes and immune microenvironments in RA. Subsequently, bone marrow-derived macrophages (BMMs) with or without receptor activator of nuclear factor kappa-B ligand (RANKL) intervention were harvested for RNA sequencing (RNA-seq) to verify FAM hub gene expressions.\nResults: Difference analysis between RA samples and controls screened 53 significant FAM regulators. Random forest algorithm for RA risk prediction was utilized to identify ten diagnostic FAM regulators (hub genes). A nomogram incorporating hub genes was developed, and decision curve analysis suggested its potential utility in clinical practice. Additionally, consensus clustering analysis of these hub genes categorized RA patients to different FAM clusters (cluster A and cluster B). To quantify FAM clusters, principal component analysis (PCA) was adopted to count FAM score of every sample. ClusterB may be more linked with osteoclastogenesis in RA characterized by RXRA, IL17RA, and TBXA2R. Additionally, cases in cluster A were associated with the immunity of activated CD4 T cell, activated CD8 T cell, eosinophil, Gamma delta T cell, immature dendritic cell, MDSC, macrophage, regulatory T cell, and Type 2 T helper cell, while cluster B was linked to CD56dim natural killer cell, Natural killer T cell, T follicular helper cell, Type 1 T helper cell immunity, which has a higher FAM score. Remarkably, RNA-seq analysis confirmed the expression trend of SREBF1, FASN, CD36, SCD1 and SCD2, consistent with bioinformatics predictions.\nConclusions: This scoring system of FAM subtypes provided promising markers and immunotherapeutic strategies for future RA treatment.", "claims": [{"id": "claim-method", "statement": "Using the “ConsensusClusterPlus” R package, different FAM patterns were identified based on FAM hub genes (19).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40777023", "locator": "sections[6] \"Subgroup classification\" paragraph 2", "quote": "Using the “ConsensusClusterPlus” R package, different FAM patterns were identified based on FAM hub genes (19)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and/or analyzed during the current study are available in the GEO repository, accession number: GSE93272.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40777023", "locator": "sections[28] \"Data availability statement\" paragraph 2", "quote": "The datasets generated and/or analyzed during the current study are available in the GEO repository, accession number: GSE93272."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Additionally, consensus clustering analysis of these hub genes categorized RA patients to different FAM clusters (cluster A and cluster B).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40777023", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Additionally, consensus clustering analysis of these hub genes categorized RA patients to different FAM clusters (cluster A and cluster B)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Additionally, consensus clustering analysis of these hub genes categorized RA patients to different FAM clusters (cluster A and cluster B).", "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:40777023"], "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:GSE93272"], "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:GSE93272"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40777023", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fimmu.2025.1611000", "sha256": "sha256:032e78ee6068a6e7ad993e98b5b4d05b6c7fe74e23910346cc846020cb4cc6e9", "bytes": 47684, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fimmu.2025.1611000", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12328365", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE93272", "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=GSE93272", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE93272", "version": null, "note": "The datasets generated and/or analyzed during the current study are available in the GEO repository, accession number: GSE93272.", 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Results", "y, which has a higher FAM score. Remarkably, RNA-seq analysis confirmed the expression trend of S", "gand (RANKL) intervention were harvested for RNA sequencing (RNA-seq) to verify FAM hub gene expressions"], "order_basis": "paper_text_order:0", "id": "assay:1"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["h unrestricted access to food and water. The rats were euthanized under isoflurane anesthesia. RNA-", "roved all studies. Female Sprague–Dawley(SD) rats, aged 8 weeks and weighing 200–220g, were pu", "h unrestricted access to food and water. The rats were euthanized under isoflurane anesthesia.", "BMMs, we flushed long bones from 8-week-old rats using warm, serum-free alpha-minimum essenti"], "order_basis": "paper_text_order:2353", "id": "assay:2"}, {"role": "data_generation", "definition_id": "cell_culture", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.77, "evidence": ["ntial medium (α-MEM). 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