Identification of key genes and immune infiltration in osteoarthritis through analysis of zinc metabolism-related genes.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:38509535", "kind": "science-record", "revision": 3, "content_hash": "sha256:31b86aacfac96f51395517577887e6a239ee83f86332c69cf8f264c265608fa5", "created_at": "2026-11-01T19:20:27Z", "updated_at": "2026-11-01T22:11:29Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key genes and immune infiltration in osteoarthritis through analysis of zinc metabolism-related genes.", "doi": "10.1186/s12891-024-07347-8", "pmid": "38509535", "authors": ["Xiaoxuan You", "Yanbo Ye", "Shufeng Lin", "Zefeng Zhang", "Huiyang Guo", "Hui Ye"], "journal": "BMC musculoskeletal disorders", "year": 2024, "abstract": "BACKGROUND: Osteoarthritis (OA) represents a prominent etiology of considerable pain and disability, and conventional imaging methods lack sensitivity in diagnosing certain types of OA. Therefore, there is a need to identify highly sensitive and efficient biomarkers for OA diagnosis. Zinc ions feature in the pathogenesis of OA. This work aimed to investugate the role of zinc metabolism-related genes (ZMRGs) in OA and the diagnostic characteristics of key genes.\nMETHODS: We obtained datasets GSE169077 and GSE55235 from the Gene Expression Omnibus (GEO) and obtained ZMRGs from MSigDB. Differential expression analysis was conducted on the GSE169077 dataset using the limma R package to identify differentially expressed genes (DEGs), and the intersection of DEGs and ZMRGs yielded zinc metabolism differential expression-related genes (ZMRGs-DEGs). The clusterProfiler R package was employed for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of ZMRGs-DEGs. Potential small molecule drugs were predicted using the CMap database, and immune cell infiltration and function in OA individuals were analyzed using the ssGSEA method. Protein-protein interaction (PPI) networks were constructed to detect Hub genes among ZMRGs-DEGs. Hub gene expression levels were analyzed in the GSE169077 and GSE55235 datasets, and their diagnostic characteristics were assessed using receiver operating characteristic (ROC) curves. The gene-miRNA interaction network of Hub genes was explored using the gene-miRNA interaction network website.\nRESULTS: We identified 842 DEGs in the GSE169077 dataset, and their intersection with ZMRGs resulted in 46 ZMRGs-DEGs. ZMRGs-DEGs were primarily enriched in functions such as collagen catabolic processes, extracellular matrix organization, metallopeptidase activity, and pathways like the IL-17 signaling pathway, Nitrogen metabolism, and Relaxin signaling pathway. Ten potential small-molecule drugs were predicted using the CMap database. OA patients exhibited distinct immune cell abundance and function compared to healthy individuals. We identified 4 Hub genes (MMP2, MMP3, MMP9, MMP13) through the PPI network, which were highly expressed in OA and demonstrated good diagnostic performance. Furthermore, two closely related miRNAs for each of the 4 Hub genes were identified.\nCONCLUSION: 4 Hub genes were identified as potential diagnostic biomarkers and therapeutic targets for OA.", "claims": [{"id": "claim-method", "statement": "The predictive capability of Hub genes was assessed by generating ROC curves and calculating the area under the curve (AUC) using the pROC R package on the GSE169077 dataset and subsequently validated on the GSE55235 dataset.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38509535", "locator": "sections[9] \"Validation of hub genes’ diagnostic capability\" paragraph 2", "quote": "The predictive capability of Hub genes was assessed by generating ROC curves and calculating the area under the curve (AUC) using the pROC R package on the GSE169077 dataset and subsequently validated on the GSE55235 dataset."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data and materials in the current study are available from the corresponding author on reasonable request.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38509535", "locator": "sections[22] \"Data availability\" paragraph 2", "quote": "The data and materials in the current study are available from the corresponding author on reasonable request."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The four hub genes demonstrated good diagnostic performance for osteoarthritis, with GSE55235 validation-set AUCs of 0.96, 0.61, 0.84, and 0.84 for MMP9, MMP2, MMP3, and MMP13, respectively.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38509535", "locator": "sections[16] \"Validation of hub gene diagnostic performance\" paragraph 2", "quote": "The results indicated that the AUCs for MMP9, MMP2, MMP3, and MMP13 in the GSE169077 dataset were 0.933, 1, 0.833, and 1, respectively."}, {"asset": "source:pmid:38509535", "locator": "sections[16] \"Validation of hub gene diagnostic performance\" paragraph 2", "quote": "In the validation dataset GSE55235, the AUCs were 0.96, 0.61, 0.84, and 0.84, respectively (Fig. 5C-D)."}, {"asset": "source:pmid:38509535", "locator": "sections[16] \"Validation of hub gene diagnostic performance\" paragraph 2", "quote": "In summary, Hub genes demonstrated good diagnostic performance in OA patients."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The four hub genes demonstrated good diagnostic performance for osteoarthritis, with GSE55235 validation-set AUCs of 0.96, 0.61, 0.84, and 0.84 for MMP9, MMP2, MMP3, and MMP13, 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:38509535"], "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:GSE169077"], "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:GSE169077"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38509535", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12891-024-07347-8", "sha256": "sha256:f6c8f9adb055a7cff9ac698f1a4d31b2aa3df3cfba194ab84fd6a259dfbf584e", "bytes": 31318, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12891-024-07347-8", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10956297", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE169077", "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=GSE169077", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE169077", "version": null, "note": "The data and materials in the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data and materials in the current study are available from the corresponding author on reasonable request.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5176138", "GSM5176139", "GSM5176140", "GSM5176141", "GSM5176142", "GSM5176143", "GSM5176144", "GSM5176145", "GSM5176146", "GSM5176147", "GSM5176148"], "sample_count": 11, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Dysregulated gene expression in human osteoarthritis cartilage", "resolution_checked_at": "2026-11-01T19:09:46Z", "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 data and materials in the current study are available from the corresponding author on reasonable request.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data and materials in the current study are available from the corresponding author on reasonable request.", "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:GSE169077 not downloaded", "asset:data:geo:GSE169077 licence not read", "asset:data:geo:GSE55235 not downloaded", "asset:data:geo:GSE55235 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "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-2", "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-3", "family": null, "specific": null, "label": "receiver operating characteristic (ROC) curves and area under the curve (AUC) calculations using the pROC R package", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "The predictive capability of Hub genes was assessed by generating ROC curves and calculating the area under the curve (AUC) using the pROC R package on the GSE169077 dataset and subsequently validated on the GSE55235 dataset."}}], "targets": [], "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": ["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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE169077", "GSE55235"], "resolved_accessions": ["GSE169077", "GSE55235"], "statements": ["The data and materials in the current study are available from the corresponding author on reasonable request."], "basis": "The paper names GSE169077, GSE55235 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": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:38509535", "data:geo:GSE169077"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE169077"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:12:45Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9970, "completion_tokens": 1872, "cached_tokens": 128}}, "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:38509535", "type": "paper", "label": "pmid:38509535"}, {"id": "source:pmid:38509535", "type": "manuscript", "label": "PMID 38509535 full text"}, {"id": "data:geo:GSE169077", "type": "dataset", "label": "GEO GSE169077"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38509535", "type": "paper", "label": "pmid:38509535"}, {"id": "source:pmid:38509535", "type": "manuscript", "label": "PMID 38509535 full text"}, {"id": "data:geo:GSE169077", "type": "dataset", "label": "GEO GSE169077"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38509535", "type": "extraction", "used": ["source:pmid:38509535"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE169077", "type": "accession_resolution", "used": ["data:geo:GSE169077"], "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:38509535", "parent_hash": "sha256:c806a5ed6bd4d42ec9dcbebca7dafcf57b6c604e25816c013bb03228a1307136", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE169077 licence not read", "asset:data:geo:GSE169077 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": "analysis", "definition_id": "differential_expression", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.7, "evidence": ["limma"], "order_basis": "analysis_only", "id": "assay:1"}]}