Identification and Validation of Potential Ferroptosis-Related Genes in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:36837498", "kind": "science-record", "revision": 4, "content_hash": "sha256:25ee4272060e16f12efe4ff9f61576e5fed419668886e54bf63b102c9bcf77b7", "created_at": "2026-11-01T19:01:27Z", "updated_at": "2026-11-01T22:51:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification and Validation of Potential Ferroptosis-Related Genes in Glucocorticoid-Induced Osteonecrosis of the Femoral Head.", "doi": "10.3390/medicina59020297", "pmid": "36837498", "authors": ["Ning Chen", "Yuan Meng", "Huixian Zhan", "Gang Li"], "journal": "Medicina (Kaunas, Lithuania)", "year": 2023, "abstract": "Background and Objectives. Glucocorticoid-induced osteonecrosis of the femoral head (GIONFH) is a serve complication of long-term administration of glucocorticoids. Previous experimental studies have shown that ferroptosis might be involved in the pathological process of GIONFH. The purpose of this study is to identify the ferroptosis-related genes and pathways of GIONFH by bioinformatics to further illustrate the mechanism of ferroptosis in SONFH through bioinformatics analysis. Materials and Methods. The GSE123568 mRNA expression profile dataset, including 30 GIONFH samples and 10 non-GIONFH samples, was downloaded from the Gene Expression Omnibus (GEO) database. Ferroptosis-related genes were obtained from the FerrDb database. First, differentially expressed genes (DEGs) were identified between the serum samples from GIONFH cases and those from controls. Ferroptosis-related DEGs were obtained from the intersection of ferroptosis-related genes and DEGs. Only ferroptosis DEGs were used for all analyses. Then, we conducted a Kyoto encyclopedia of genome (KEGG) and gene ontology (GO) pathway enrichment analysis. We constructed a protein-protein interaction (PPI) network to screen out hub genes. Additionally, the expression levels of the hub genes were validated in an independent dataset GSE10311. Results. A total of 27 ferroptosis-related DEGs were obtained between the peripheral blood samples of GIONFH cases and non-GIONFH controls. Then, GO, and KEGG pathway enrichment analysis revealed that ferroptosis-related DEGs were mainly enriched in the regulation of the apoptotic process, oxidation-reduction process, and cell redox homeostasis, as well as HIF-1, TNF, FoxO signaling pathways, and osteoclast differentiation. Eight hub genes, including TLR4, PTGS2, SNCA, MAPK1, CYBB, SLC2A1, TXNIP, and MAP3K5, were identified by PPI network analysis. The expression levels of TLR4, TXNIP and MAP3K5 were further validated in the dataset GSE10311. Conclusion. A total of 27 ferroptosis-related DEGs involved in GIONFH were identified via bioinformatics analysis. TLR4, TXNIP, and MAP3K5 might serve as potential biomarkers and drug targets for GIONFH.", "claims": [{"id": "claim-method", "statement": "The linear model for microarray data (LIMMA) package was used to identify DEGs between the serum samples from GIONFH cases and those from controls.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36837498", "locator": "sections[5] \"2.3. Ferroptosis-Related DEGs Analysis\" paragraph 2", "quote": "The linear model for microarray data (LIMMA) package was used to identify DEGs between the serum samples from GIONFH cases and those from controls."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:36837498", "locator": "sections[19] \"Data Availability Statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 27 ferroptosis-related DEGs were obtained between the peripheral blood samples of GIONFH cases and non-GIONFH controls.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:36837498", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "A total of 27 ferroptosis-related DEGs were obtained between the peripheral blood samples of GIONFH cases and non-GIONFH controls."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 27 ferroptosis-related DEGs were obtained between the peripheral blood samples of GIONFH cases and non-GIONFH controls.", "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:36837498"], "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:GSE10311"], "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:GSE10311"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:36837498", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3390/medicina59020297", "sha256": "sha256:32e70b273d84da2877f7725896b5edfb6905f3af05ced9866455f1230084c9d7", "bytes": 40618, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3390/medicina59020297", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC9962586", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE10311", "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=GSE10311", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE10311", "version": null, "note": "Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM260302", "GSM260303", "GSM260304", "GSM260305", "GSM260306", "GSM260307", "GSM260308", "GSM260309", "GSM260310", "GSM260311", "GSM260312", "GSM260313", "GSM260314", "GSM260321", "GSM260322", "GSM260323", "GSM260324", "GSM260325", "GSM260326", "GSM260327", "GSM260328"], "sample_count": 21, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Systematic Assessment of Human Osteoblast Transcriptome in Resting and Induced Primary Cells", "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: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": "Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022).", "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}}], "gaps": ["asset:data:geo:GSE10311 not downloaded", "asset:data:geo:GSE10311 licence not read", "asset:data:geo:GSE123568 not downloaded", "asset:data:geo:GSE123568 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 linear model for microarray data (LIMMA) package was used to identify DEGs between the serum samples from GIONFH cases and those from controls."}}, {"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": "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"}}], "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. The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE123568", "GSE10311"], "resolved_accessions": ["GSE123568", "GSE10311"], "statements": ["Publicly available datasets were analyzed in this study. These datasets can be found at the following websites: FerrDb (http://www.zhounan.org/ferrdb/current/, accessed on 1 October 2022), GSE123568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE123568, accessed on 1 October 2022) and GSE10311 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE10311, accessed on 1 October 2022)."], "basis": "The paper names GSE123568, GSE10311 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:36837498", "data:geo:GSE10311"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE10311"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:31:41Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 12652, "completion_tokens": 1923, "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:36837498", "type": "paper", "label": "pmid:36837498"}, {"id": "source:pmid:36837498", "type": "manuscript", "label": "PMID 36837498 full text"}, {"id": "data:geo:GSE10311", "type": "dataset", "label": "GEO GSE10311"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:36837498", "type": "paper", "label": "pmid:36837498"}, {"id": "source:pmid:36837498", "type": "manuscript", "label": "PMID 36837498 full text"}, {"id": "data:geo:GSE10311", "type": "dataset", "label": "GEO GSE10311"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-36837498", "type": "extraction", "used": ["source:pmid:36837498"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE10311", "type": "accession_resolution", "used": ["data:geo:GSE10311"], "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:36837498", "parent_hash": "sha256:d3fa0ef14e05b46ed63b9f53f9f72da4c36d689b12e7fdb4d5ef2a8554fe21b1", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE10311 licence not read", "asset:data:geo:GSE10311 not downloaded", "asset:data:geo:GSE123568 licence not read", "asset:data:geo:GSE123568 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 linear model for microarray data (LIMMA) package was used to identify DEGs between the serum samples from GIONFH cases and those from controls."], "order_basis": "analysis_only", "id": "assay:1"}]}