Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid Arthritis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36317112", "kind": "science-record", "revision": 4, "content_hash": "sha256:02bf397723c8a0cda2ea3e4d74b21780c8b3930320a8ad4f0b4efb81923bb6c3", "created_at": "2026-11-01T18:15:44Z", "updated_at": "2026-11-01T22:08:00Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of Hub Genes for Predicting Treatment Targets and Immune Landscape in Rheumatoid Arthritis.", "doi": "10.1155/2022/8023779", "pmid": "36317112", "authors": ["Xinling He", "Ji Yin", "Mingfang Yu", "Haoyu Wang", "Jiao Qiu", "Aiyang Wang", "Xueyi He", "Xiao Wu"], "journal": "BioMed research international", "year": 2022, "abstract": "Background: Rheumatoid arthritis (RA) is recognized as a chronic inflammatory disease featured by pathological synovial inflammation. Currently, the underlying pathophysiological mechanisms of RA remain unclear. In the study, we attempted to explore the underlying mechanisms of RA and provide potential targets for the therapy of RA via bioinformatics analysis.\nMethods: We downloaded four microarray datasets (GSE77298, GSE55235, GSE12021, and GSE55457) from the GEO database. Firstly, GSE77298 and GSE55457 were identified DEGs by the \"limma\" and \"sva\" packages of R software. Then, we performed GO, KEGG, and GSEA enrichment analyses to further analyze the function of DEGs. Hub genes were screened using LASSO analysis and SVM-RFE analysis. To further explore the differences of the expression of hub genes in healthy control and RA patient synovial tissues, we calculated the ROC curves and AUC. The expression levels of hub genes were verified in synovial tissues of normal and RA rats by qRT-PCR and western blot. Furthermore, the CIBERSORTx was implemented to assess the differences of infiltration in 22 immune cells between normal and RA synovial tissues. We explored the association between hub genes and infiltrating immune cells.\nResults: CRTAM, CXCL13, and LRRC15 were identified as RA's potential hub genes by machine learning and LASSO algorithms. In addition, we verified the expression levels of three hub genes in the synovial tissue of normal and RA rats by PCR and western blot. Moreover, immune cell infiltration analysis showed that plasma cells, T follicular helper cells, M0 macrophages, M1 macrophages, and gamma delta T cells may be engaged in the development and progression of RA.\nConclusions: In brief, our study identified and validated that three hub genes CRTAM, CXCL13, and LRRC15 might involve in the pathological development of RA, which could provide novel perspectives for the diagnosis and treatment with RA.", "claims": [{"id": "claim-method", "statement": "The Wilcox test was used to compare the intergroup difference between two groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36317112", "locator": "sections[12] \"2.10. Statistical Analysis\" paragraph 2", "quote": "The Wilcox test was used to compare the intergroup difference between two groups."}], "state": "complete"}, {"id": "claim-data-access", "statement": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36317112", "locator": "sections[25] \"Data Availability\" paragraph 2", "quote": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "LASSO regression and SVM-RFE analyses identified three RA-related hub genes: LRRC15, CXCL13, and CRTAM.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36317112", "locator": "sections[16] \"3.3. Identification of Hub Genes\" paragraph 2", "quote": "By combining LASSO regression analyses and SVM-RFE analyses, three hub genes related to RA were screened, namely, LRRC15, CXCL13, and CRTAM (Figure 3(c))."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "LASSO regression and SVM-RFE analyses identified three RA-related hub genes: LRRC15, CXCL13, and CRTAM.", "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:36317112"], "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:GSE12021"], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "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:GSE12021"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36317112", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/8023779", "sha256": "sha256:cd920e266280f41dc2d7561b484c37dbe6f373eeb033a0b410a4c11d59731e03", "bytes": 33416, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/8023779", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9617710", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12021", "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=GSE12021", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12021", "version": null, "note": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM302859", "GSM302864", "GSM302866", "GSM302870", "GSM302872", "GSM302874", "GSM302876", "GSM302878", "GSM302880", "GSM302881", "GSM302882", "GSM302895", "GSM302896", "GSM302897", "GSM302900", "GSM302905", "GSM302924", "GSM302926", "GSM302927", "GSM302929", "GSM302930", "GSM302932", "GSM302933", "GSM302934", "GSM302943", "GSM302944", "GSM303326", "GSM303339", "GSM303341", "GSM303355", "GSM303356", "GSM303357", "GSM303358", "GSM303359", "GSM303360", "GSM303361", "GSM303362", "GSM303363", "GSM303364", "GSM303365", "GSM303366", "GSM303367", "GSM303368", "GSM303369", "GSM303370", "GSM303377", "GSM303520", "GSM303521", "GSM303522", "GSM303523", "GSM303524", "GSM303525", "GSM303530", "GSM303531", "GSM303532", "GSM303533", "GSM303534"], "sample_count": 57, "group_sizes": null, "group_sizes_basis": null, "platform": "96;97", "taxon": "Homo sapiens", "title": "Identification of inter-individual and gene-specific variances in mRNA expression profiles in the RA SM", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE55235", "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=GSE55235", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55235", "version": null, "note": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1332201", "GSM1332202", "GSM1332203", "GSM1332204", "GSM1332205", "GSM1332206", "GSM1332207", "GSM1332208", "GSM1332209", "GSM1332210", "GSM1332211", "GSM1332212", "GSM1332213", "GSM1332214", "GSM1332215", "GSM1332216", "GSM1332217", "GSM1332218", "GSM1332219", "GSM1332220", "GSM1332221", "GSM1332222", "GSM1332223", "GSM1332224", "GSM1332225", "GSM1332226", "GSM1332227", "GSM1332228", "GSM1332229", "GSM1332230"], "sample_count": 30, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE55457", "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=GSE55457", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55457", "version": null, "note": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1337304", "GSM1337305", "GSM1337306", "GSM1337307", "GSM1337308", "GSM1337309", "GSM1337310", "GSM1337311", "GSM1337312", "GSM1337313", "GSM1337314", "GSM1337315", "GSM1337316", "GSM1337317", "GSM1337318", "GSM1337319", "GSM1337320", "GSM1337321", "GSM1337322", "GSM1337323", "GSM1337324", "GSM1337325", "GSM1337326", "GSM1337327", "GSM1337328", "GSM1337329", "GSM1337330", "GSM1337331", "GSM1337332", "GSM1337333", "GSM1337334", "GSM1337335", "GSM1337336"], "sample_count": 33, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Identification of rheumatoid arthritis and osteoarthritis patients by transcriptome-based rule set generation [Jena]", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE77298", "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=GSE77298", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE77298", "version": null, "note": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "All data generated or analyzed during this study are included in this published article. Requests for material should be made to the corresponding authors.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2048265", "GSM2048266", "GSM2048267", "GSM2048268", "GSM2048269", "GSM2048270", "GSM2048271", "GSM2048272", "GSM2048273", "GSM2048274", "GSM2048275", "GSM2048276", "GSM2048277", "GSM2048278", "GSM2048279", "GSM2048280", "GSM2048281", "GSM2048282", "GSM2048283", "GSM2048284", "GSM2048285", "GSM2048286", "GSM2048287"], "sample_count": 23, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Synovial biopsies of rheumatoid arthritis and healthy controls", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE12021 not downloaded", "asset:data:geo:GSE12021 licence not read", "asset:data:geo:GSE55235 not downloaded", "asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55457 not downloaded", "asset:data:geo:GSE55457 licence not read", "asset:data:geo:GSE77298 not downloaded", "asset:data:geo:GSE77298 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The Wilcox test was used to compare the intergroup difference between two groups."}}, {"id": "method-2", "family": "differential_expression", "specific": "limma_voom", "label": "Differential expression analysis", "dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["count_matrix_with_condition"], "evidence": {"score": 0.7, "band": "medium", "quote": "limma"}}, {"id": "method-3", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "SVM"}}, {"id": "method-4", "family": "network_analysis", "specific": "pathway_enrichment", "label": "Network / pathway analysis", "dsl_operations": ["pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.8, "band": "high", "quote": "GO enrichment"}}], "targets": [], "gaps": ["method.reader_differs_from_extractor", "method.group_comparison_wilcoxon"]}, "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": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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Furthermore, th", "enes in the synovial tissue of normal and RA rats by PCR and western blot. Moreover, immune ce", "al Design Sixteen Sprague-Dawley (160-180 g) rats were adaptive feeding for one week, half male and", "for one week, half male and half female. All rats were purchased from the Experimental Animal Cente"], "order_basis": "paper_text_order:1065", "id": "assay:1"}, {"role": "data_generation", "definition_id": "western_blot", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["tissues of normal and RA rats by qRT-PCR and western blot. Furthermore, the CIBERSORTx was implemented", "vial tissue of normal and RA rats by PCR and western blot. 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