Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36468029", "kind": "science-record", "revision": 3, "content_hash": "sha256:49c815152de9583189402d76715237b5e62acf4f91243d264e1a9330f51381d8", "created_at": "2026-11-01T19:00:57Z", "updated_at": "2026-11-01T22:08:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of susceptibility modules and hub genes of osteoarthritis by WGCNA analysis.", "doi": "10.3389/fgene.2022.1036156", "pmid": "36468029", "authors": ["Yanchao Wang", "Wenjun Zhou", "Yan Chen", "Dong He", "Zhen Qin", "Zhao Wang", "Song Liu", "Lei Zhou", "Jianwen Su", "Chi Zhang"], "journal": "Frontiers in genetics", "year": 2022, "abstract": "Osteoarthritis (OA) is a major cause of pain, disability, and social burden in the elderly throughout the world. Although many studies focused on the molecular mechanism of OA, its etiology remains unclear. Therefore, more biomarkers need to be explored to help early diagnosis, clinical outcome measurement, and new therapeutic target development. Our study aimed to retrieve the potential hub genes of osteoarthritis (OA) by weighted gene co-expression network analysis (WGCNA) and assess their clinical utility for predicting OA. Here, we integrated WGCNA to identify novel OA susceptibility modules and hub genes. In this study, we first selected 477 and 834 DEGs in the GSE1919 and the GSE55235 databases, respectively, from the Gene Expression Omnibus (GEO) website. Genes with p-value<0.05 and | log2FC | > 1 were included in our analysis. Then, WGCNA was conducted to build a gene co-expression network, which filtered out the most relevant modules and screened out 23 overlapping WGCNA-derived hub genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses elucidated that these hub genes were associated with cell adhesion molecules pathway, leukocyte activation, and inflammatory response. In addition, we conducted the protein-protein interaction (PPI) network in 23 hub genes, and the top four upregulated hub genes were sorted out (CD4, SELL, ITGB2, and CD52). Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789). After that, a single-sample gene set enrichment (ssGSEA) analysis was performed to discover immune cell infiltration in OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that those candidate genes were significantly upregulated in the OA groups compared with normal groups. We successfully constructed a co-expression network based on WGCNA and found out that OA-associated susceptibility modules and hub genes, which may provide further insight into the development of pre-symptomatic diagnosis, may contribute to understanding the molecular mechanism study of OA risk genes.", "claims": [{"id": "claim-method", "statement": "We computed the “WGCNA” R package to construct a gene co-expression network of OA.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36468029", "locator": "sections[6] \"WGCNA (weighted gene co-expression network analysis)\" paragraph 2", "quote": "We computed the “WGCNA” R package to construct a gene co-expression network of OA."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36468029", "locator": "sections[23] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The nomogram model showed good performance in predicting osteoarthritis risk (C-index = 0.76) and diagnostic efficacy by ROC curves (AUC = 0.789).", "kind": "quantitative", "target": {"value": 0.789, "unit": "auc", "tolerance": null, "source": "Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789)."}, "evidence": [{"asset": "source:pmid:36468029", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "Moreover, our nomogram model showed good performance in predicting the risk of OA (C-index = 0.76), and this model proved to be efficient in diagnosis by ROC curves (AUC = 0.789)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The nomogram model showed good performance in predicting osteoarthritis risk (C-index = 0.76) and diagnostic efficacy by ROC curves (AUC = 0.789).", "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:36468029"], "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:GSE1919"], "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:GSE1919"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36468029", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2022.1036156", "sha256": "sha256:20e2a8a4876448f4a7ebde709cc98b59092c1a83900d5bdb29994911d651a594", "bytes": 74167, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2022.1036156", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9718428", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE1919", "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=GSE1919", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE1919", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM34379", "GSM34383", "GSM34385", "GSM34388", "GSM34391", "GSM34393", "GSM34394", "GSM34395", "GSM34396", "GSM34397", "GSM34398", "GSM34399", "GSM34400", "GSM34401", "GSM34402"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "91", "taxon": "Homo sapiens", "title": "Rheumatoid arthritis", "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:GSE51588", "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=GSE51588", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE51588", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1248759", "GSM1248760", "GSM1248761", "GSM1248762", "GSM1248763", "GSM1248764", "GSM1248765", "GSM1248766", "GSM1248767", "GSM1248768", "GSM1248769", "GSM1248770", "GSM1248771", "GSM1248772", "GSM1248773", "GSM1248774", "GSM1248775", "GSM1248776", "GSM1248777", "GSM1248778", "GSM1248779", "GSM1248780", "GSM1248781", "GSM1248782", "GSM1248783", "GSM1248784", "GSM1248785", "GSM1248786", "GSM1248787", "GSM1248788", "GSM1248789", "GSM1248790", "GSM1248791", "GSM1248792", "GSM1248793", "GSM1248794", "GSM1248795", "GSM1248796", "GSM1248797", "GSM1248798", "GSM1248799", "GSM1248800", "GSM1248801", "GSM1248802", "GSM1248803", "GSM1248804", "GSM1248805", "GSM1248806", "GSM1248807", "GSM1248808"], "sample_count": 50, "group_sizes": null, "group_sizes_basis": null, "platform": "13497", "taxon": "Homo sapiens", "title": "Genome-wide Expression Profiles of Subchondral Bone in Osteoarthritis", "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": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588.", "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}}], "gaps": ["asset:data:geo:GSE1919 not downloaded", "asset:data:geo:GSE1919 licence not read", "asset:data:geo:GSE51588 not downloaded", "asset:data:geo:GSE51588 licence not read", "asset:data:geo:GSE55235 not downloaded", "asset:data:geo:GSE55235 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "network_analysis", "specific": "ppi_network", "label": "Network / pathway analysis", "dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["edge_list"], "evidence": {"score": 0.7, "band": "medium", "quote": "protein-protein interaction"}}, {"id": "method-2", "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": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "Weighted gene co-expression network analysis (WGCNA)", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "We computed the “WGCNA” R package to construct a gene co-expression network of OA."}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 0.789, "unit": "auc", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. No tolerance is published because the paper states none."}], "gaps": ["method.reader_named_unmapped"]}, "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": ["build_graph", "centrality_scores", "pathway_enrich"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: ppi_network."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE1919", "GSE55235", "GSE51588"], "resolved_accessions": ["GSE1919", "GSE55235", "GSE51588"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found below: https://www.ncbi.nlm.nih.gov/, GSE1919; https://www.ncbi.nlm.nih.gov/, GSE55235; https://www.ncbi.nlm.nih.gov/, GSE51588."], "basis": "The paper names GSE1919, GSE55235, GSE51588 in Gene Expression Omnibus (GEO) and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:36468029", "data:geo:GSE1919"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE1919"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:18:11Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 21396, "completion_tokens": 1694, "cached_tokens": 264}}, "human_critique": null, "stages": [{"id": "extraction", "state": "complete", "reader": "MiniMax-M3.1-Flash", "provider": "minimax"}], "gaps": ["review.independent_reader", "review.machine_critique", "review.human_critique"]}, "execution": {"state": "absent", "status": "not_run", "mode": null, "runs": [], "gaps": ["execution.not_run"]}, "provenance": {"entities": [{"id": "pmid:36468029", "type": "paper", "label": "pmid:36468029"}, {"id": "source:pmid:36468029", "type": "manuscript", "label": "PMID 36468029 full text"}, {"id": "data:geo:GSE1919", "type": "dataset", "label": "GEO GSE1919"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36468029", "type": "paper", "label": "pmid:36468029"}, {"id": "source:pmid:36468029", "type": "manuscript", "label": "PMID 36468029 full text"}, {"id": "data:geo:GSE1919", "type": "dataset", "label": "GEO GSE1919"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36468029", "type": "extraction", "used": ["source:pmid:36468029"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE1919", "type": "accession_resolution", "used": ["data:geo:GSE1919"], "agent": "agent:corpus-assay-engine"}], "agents": [{"id": "agent:corpus-assay-engine", "type": "software", "label": "Corpus assay engine"}, {"id": "agent:minimax-reader", "type": "software", "label": "MiniMax literature reader"}], "source_run_id": "reading-sci-2026-11-01", "dsl_catalogue_fingerprint": "343fb30756ba6ec3", "capability_table_fingerprint": "2cb3e42f047d2ecf", "snapshot_id": "ba34b49490d9bfaf"}, "lineage": {"parent_id": "pmid:36468029", "parent_hash": "sha256:7a9ee2cbf2cec74e7050204324fc4c6f68a0eb3e46a70819abc3c459e8a835b8", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE1919 licence not read", "asset:data:geo:GSE1919 not downloaded", "asset:data:geo:GSE51588 licence not read", "asset:data:geo:GSE51588 not downloaded", "asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55235 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "ihc", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["OA. Finally, human primary synoviocytes and immunohistochemistry study of synovial tissues confirmed that tho"], "order_basis": "paper_text_order:1813", "id": "assay:1"}, {"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": ["with 0.05% trypsin. The isolated cells were cultured in DMEM/F12 medium (Gibco, Thermo Fisher) suppl"], "order_basis": "paper_text_order:4169", "id": "assay:2"}, {"role": "analysis", "definition_id": "network_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["build_graph", "centrality_scores", "pathway_enrich"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["protein-protein interaction"], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}