Identification of Inflammation-Related Genes and Exploration of Regulatory Mechanisms in Patients with Osteonecrosis of the Femoral Head.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36193326", "kind": "science-record", "revision": 5, "content_hash": "sha256:c8a1c44a75e7ae5c75a814134ab02e780ba8a087eec2dfb4e33d7c90aafadfa8", "created_at": "2026-11-01T18:15:30Z", "updated_at": "2026-11-01T22:50:14Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Inflammation-Related Genes and Exploration of Regulatory Mechanisms in Patients with Osteonecrosis of the Femoral Head.", "doi": "10.1155/2022/4501186", "pmid": "36193326", "authors": ["Tong Li", "Cheng Huang", "Jinhui Ma", "Ran Ding", "Qidong Zhang", "Weiguo Wang"], "journal": "BioMed research international", "year": 2022, "abstract": "Background: Osteonecrosis of the femoral head (ONFH) is a disabling orthopedic disease, which is impacted by infiltration of immune cells. Thus, the aim of the current research was to determine the inflammation-related biomarkers in ONFH.\nMethods: GSE123568 dataset with control and steroid-induced osteonecrosis of the femoral head (SONFH) samples were downloaded from Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) were detected by limma R package and weighted gene co-expression network analysis (WGCNA) was used to explore the co-expression genes and modules. We obtained inflammation-related genes (IRGs) from the Molecular Signatures Database (MSigDB). Then, the IRGs associated with SONFH (IRGs-SONFH) were screened out and analyzed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. A protein-protein interaction (PPI) network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, and hub genes were identified by the MCODE algorithm. Based on the hub genes, we constructed a lncRNA-miRNA-mRNA network.\nResults: We identified 535 DEGs between control and SONFH samples. The WGCNA clearly indicated that the brown module was most significantly associated with SONFH. We identified 25 IRGs-SONFH through WGCNA module genes, DEGs and IRGs. A total of 4 hub genes (CD14, CYBB, NOD2, and TLR1) were identified by Cytoscape. Receiver operating characteristic (ROC) curve analysis determined that the expressions of the four genes could distinguish SONFH from controls as evidenced by the area under the curve (AUC) greater than 0.7. Finally, we constructed a competitive endogenous RNA (ceRNA) network which included 67 lncRNAs, 1 miRNA (hsa-miR-320a), and 1 mRNA (NOD2).\nConclusions: Our study identified 4 hub genes as potential inflammation-related biomarkers of SONFH. Moreover, we proposed a ceRNA network of lncRNAs targeting hsa-miR-320a, hsa-miR-320a, and NOD2 as a potential RNA regulatory pathway that controls disease progression in ONFH.", "claims": [{"id": "claim-method", "statement": "The limma, a package in the R language, was used to identify DEGs with the cut-off point of adjusted p-value (false discovery rate) <0.05 and |Log2fold change| >1.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36193326", "locator": "sections[4] \"2.2. Identification of DEGs\" paragraph 2", "quote": "The limma, a package in the R language, was used to identify DEGs with the cut-off point of adjusted p-value (false discovery rate) <0.05 and |Log2fold change| >1."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated and analyzed during the current study are available in the GEO, MSigDB, STRING, DGIdb, and miRNet databases. GEO (https://www.ncbi.nlm.nih.gov/geo/); MSigDB (https://www.broadinstitute.org/msigdb); STRING (https://string-db.org); DGIdb (https://www.dgidb.org); miRNet (https://www.mirnet.ca).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36193326", "locator": "sections[30] \"Data Availability\" paragraph 2", "quote": "The datasets generated and analyzed during the current study are available in the GEO, MSigDB, STRING, DGIdb, and miRNet databases. GEO (https://www.ncbi.nlm.nih.gov/geo/); MSigDB (https://www.broadinstitute.org/msigdb); STRING (https://string-db.org); DGIdb (https://www.dgidb.org); miRNet (https://www.mirnet.ca)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Using limma analysis of GSE123568, the study identified 535 DEGs and ultimately identified and validated four inflammation-related biomarker genes for SONFH: CD14, CYBB, NOD2, and TLR1.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36193326", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "We identified 535 DEGs between control and SONFH samples."}, {"asset": "source:pmid:36193326", "locator": "sections[27] \"5. Conclusions\" paragraph 2", "quote": "This study identified and validated 4 hub genes, CD14, CYBB, NOD2, and TLR1, as potential inflammation-related biomarkers of SONFH, and provided clues to the mechanism of disease development of SONFH at the transcriptome level."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Using limma analysis of GSE123568, the study identified 535 DEGs and ultimately identified and validated four inflammation-related biomarker genes for SONFH: CD14, CYBB, NOD2, and TLR1.", "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:36193326"], "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:GSE123568"], "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:GSE123568"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36193326", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1155/2022/4501186", "sha256": "sha256:984326d5780ccaf553864116815346d45f35b6f12902e5bcdabb9d3da6d2b287", "bytes": 30800, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1155/2022/4501186", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9526608", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE123568", "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=GSE123568", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE123568", "version": null, "note": "The datasets generated and analyzed during the current study are available in the GEO, MSigDB, STRING, DGIdb, and miRNet databases. 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GEO (https://www.ncbi.nlm.nih.gov/geo/); MSigDB (https://www.broadinstitute.org/msigdb); STRING (https://string-db.org); DGIdb (https://www.dgidb.org); miRNet (https://www.mirnet.ca).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3507251", "GSM3507252", "GSM3507253", "GSM3507254", "GSM3507255", "GSM3507256", "GSM3507257", "GSM3507258", "GSM3507259", "GSM3507260", "GSM3507261", "GSM3507262", "GSM3507263", "GSM3507264", "GSM3507265", "GSM3507266", "GSM3507267", "GSM3507268", "GSM3507269", "GSM3507270", "GSM3507271", "GSM3507272", "GSM3507273", "GSM3507274", "GSM3507275", "GSM3507276", "GSM3507277", "GSM3507278", "GSM3507279", "GSM3507280", "GSM3507281", "GSM3507282", "GSM3507283", "GSM3507284", "GSM3507285", "GSM3507286", "GSM3507287", "GSM3507288", "GSM3507289", "GSM3507290"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "15207", "taxon": "Homo sapiens", "title": "Identification of Potential Biomarkers for Improving the Precision of Early Detection of Steroid-induced Osteonecrosis of the Femoral Head", "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:GSE89587", "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=GSE89587", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE89587", "version": null, "note": "The datasets generated and analyzed during the current study are available in the GEO, MSigDB, STRING, DGIdb, and miRNet databases. 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GEO (https://www.ncbi.nlm.nih.gov/geo/); MSigDB (https://www.broadinstitute.org/msigdb); STRING (https://string-db.org); DGIdb (https://www.dgidb.org); miRNet (https://www.mirnet.ca).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2384936", "GSM2384937", "GSM2384938", "GSM2384939", "GSM2384940", "GSM2384941", "GSM2384942", "GSM2384943", "GSM2384944", "GSM2384945", "GSM2384946", "GSM2384947", "GSM2384948", "GSM2384949", "GSM2384950", "GSM2384951", "GSM2384952", "GSM2384953", "GSM2384954", "GSM2384955"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "21439", "taxon": "Herpesvirus saimiri (strain 11); JC polyomavirus; Human immunodeficiency virus 1; Human gammaherpesvirus 8; Human alphaherpesvirus 1; Human betaherpesvirus 5; human gammaherpesvirus 4; Human betaherpesvirus 6B; Betapolyomavirus macacae; Human alphaherpesvirus 2; Betapolyomavirus hominis; Homo sapiens; Macacine alphaherpesvirus 1; Merkel cell polyomavirus", "title": "MicroRNAs expression different in Serum between Trauma-induced  osteonecrosis  of  the  femoral  head (TIONFH) and healing patients", "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:GSE123568 not downloaded", "asset:data:geo:GSE123568 licence not read", "asset:data:geo:GSE89587 not downloaded", "asset:data:geo:GSE89587 licence not read"]}, "analysis": {"state": "complete", "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": 1.0, "band": "verbatim", "quote": "The limma, a package in the R language, was used to identify DEGs with the cut-off point of adjusted p-value (false discovery rate) <0.05 and |Log2fold change| >1."}}, {"id": "method-2", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman's correlation"}}, {"id": "method-3", "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"}}], "targets": [], "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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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:36193326", "data:geo:GSE123568"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE123568"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:08:07Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 9870, "completion_tokens": 2408, "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:36193326", "type": "paper", "label": "pmid:36193326"}, {"id": "source:pmid:36193326", "type": "manuscript", "label": "PMID 36193326 full text"}, {"id": "data:geo:GSE123568", "type": "dataset", "label": "GEO GSE123568"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36193326", "type": "paper", "label": "pmid:36193326"}, {"id": "source:pmid:36193326", "type": "manuscript", "label": "PMID 36193326 full text"}, {"id": "data:geo:GSE123568", "type": "dataset", "label": "GEO GSE123568"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36193326", "type": "extraction", "used": ["source:pmid:36193326"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE123568", "type": "accession_resolution", "used": ["data:geo:GSE123568"], "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:36193326", "parent_hash": "sha256:05091addd9bc0599cb009e45aa7374c2bbad5af276f6343c667973320ddf0869", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE123568 licence not read", "asset:data:geo:GSE123568 not downloaded", "asset:data:geo:GSE89587 licence not read", "asset:data:geo:GSE89587 not downloaded", "execution.not_run", "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": 1.0, "evidence": ["The limma, a package in the R language, was used to identify DEGs with the cut-off point of adjusted p-value (false discovery rate) <0.05 and |Log2fold change| >1."], "order_basis": "analysis_only", "id": "assay:1"}]}