Identification of Hub Genes and Pathways Associated with Oxidative Stress of Cartilage in Osteonecrosis of Femoral Head Using Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35118903", "kind": "science-record", "revision": 5, "content_hash": "sha256:a3bb46f7cc200e3313ee3417965f2d2b76114b52d70c76175faa1444107cd4c4", "created_at": "2026-11-01T17:36:52Z", "updated_at": "2026-11-01T22:48:24Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of Hub Genes and Pathways Associated with Oxidative Stress of Cartilage in Osteonecrosis of Femoral Head Using Bioinformatics Analysis.", "doi": "10.1177/19476035221074000", "pmid": "35118903", "authors": ["Wei Shi", "Xinglong Zhang", "Chunlei Xu", "Ran Pang", "Zhenqi Fan", "Xin Wan", "Zhaohui Jiang", "Hui Li", "Zhijun Li", "Huafeng Zhang"], "journal": "Cartilage", "year": 2022, "abstract": "OBJECTIVE: This study aimed to identify the hub genes and pathways of genes related to oxidative stress of cartilage in osteonecrosis of femoral head (ONFH), and to predict the transcription factors of the hub genes.\nMETHODS: The GSE74089 was obtained from the Gene Expression Omnibus (GEO) database, including 4 necrotic tissues and 4 normal tissues, and the differentially expressed genes (DEGs) were identified by limma package in R language. Simultaneously, we searched for the genes related to oxidative stress in the Gene Ontology (GO) database. GO and signaling pathways analysis were performed using DAVID, Metascape, and GSEA. Protein-protein interaction (PPI) network was constructed using the STRING database, and the Degree algorithm of Cytoscape software was used to screen for hub genes. Finally, the NetworkAnalyst web tool was used to find the hub genes' transcriptional factors (TFs).\nRESULTS: In total, 440 oxidative stress-related genes were found in GSE74089 and GO database, and 88 of them were significantly differentially expressed. These genes were mainly involved in several signaling pathways, such as MAPK signaling pathway, PI3K-AKT-mTOR signaling pathway, FOXO signaling pathway. The top 10 hub genes were JUN, FOXO3, CASP3, JAK2, RELA, EZH2, ABL1, PTGS2, FBXW7, MCL1. Besides, TFAP2A, GATA2, SP1, and E2F1 may be the key regulatory factors of hub genes.\nCONCLUSIONS: We identified some hub genes and signaling pathways associated with oxidative stress in ONFH through a series of bioinformatics analyses.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were screened using the limma package in R.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35118903", "locator": "sections[4] \"Data Preprocessing and Integration\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were screened using the limma package in R."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profile of GSE74089 was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo), which is a database repository of high-throughput gene expression data, hybridization arrays, chips, and microarrays. The data set GSE74089 was based on the GPL13497 platform (Agilent-026652 Whole Human Genome Microarray 4 x 44K v2) and consisted of 8 femoral cartilage samples, including 4 ONFH samples (3 males and 1 female) and 4 normal samples (3 males and 1 female).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35118903", "locator": "sections[3] \"Data Source\" paragraph 2", "quote": "The gene expression profile of GSE74089 was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo), which is a database repository of high-throughput gene expression data, hybridization arrays, chips, and microarrays. The data set GSE74089 was based on the GPL13497 platform (Agilent-026652 Whole Human Genome Microarray 4 x 44K v2) and consisted of 8 femoral cartilage samples, including 4 ONFH samples (3 males and 1 female) and 4 normal samples (3 males and 1 female)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "In total, 440 oxidative stress–related genes were found in GSE74089 and GO database, and 88 of them were significantly differentially expressed.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35118903", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "In total, 440 oxidative stress–related genes were found in GSE74089 and GO database, and 88 of them were significantly differentially expressed."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "In total, 440 oxidative stress–related genes were found in GSE74089 and GO database, and 88 of them were significantly differentially expressed.", "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:35118903"], "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:GSE74089"], "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:GSE74089"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35118903", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1177/19476035221074000", "sha256": "sha256:9caeb1b0d30636cee181d5102c4544078e0659f202fb4f62a3ddc2d0890bafaf", "bytes": 31178, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1177/19476035221074000", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9137318", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE74089", "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=GSE74089", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE74089", "version": null, "note": "The gene expression profile of GSE74089 was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo), which is a database repository of high-throughput gene expression data, hybridization arrays, chips, and microarrays. The data set GSE74089 was based on the GPL13497 platform (Agilent-026652 Whole Human Genome Microarray 4 x 44K v2) and consisted of 8 femoral cartilage samples, including 4 ONFH samples (3 males and 1 female) and 4 normal samples (3 males and 1 female).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression profile of GSE74089 was downloaded from the Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo), which is a database repository of high-throughput gene expression data, hybridization arrays, chips, and microarrays. The data set GSE74089 was based on the GPL13497 platform (Agilent-026652 Whole Human Genome Microarray 4 x 44K v2) and consisted of 8 femoral cartilage samples, including 4 ONFH samples (3 males and 1 female) and 4 normal samples (3 males and 1 female).", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM1909502", "GSM1909503", "GSM1909504", "GSM1909505", "GSM1909506", "GSM1909507", "GSM1909508", "GSM1909509"], "sample_count": 8, "group_sizes": null, "group_sizes_basis": null, "platform": "13497", "taxon": "Homo sapiens", "title": "Gene expression profiling of hip cartilage with necrosis of femoral head", "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:GSE74089 not downloaded", "asset:data:geo:GSE74089 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": "Differentially expressed genes (DEGs) were screened using the limma package in R."}}, {"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"}}], "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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