Comprehensive bioinformatics analysis uncover molecular pathways shared between osteoarthritis and atherosclerosis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40335993", "kind": "science-record", "revision": 3, "content_hash": "sha256:8cc90bfa1186a427eb486d19a627917745475adf8498b64d3d9b56e15f4b0952", "created_at": "2026-11-01T20:30:30Z", "updated_at": "2026-11-01T22:14:02Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive bioinformatics analysis uncover molecular pathways shared between osteoarthritis and atherosclerosis.", "doi": "10.1186/s12891-025-08563-6", "pmid": "40335993", "authors": ["Yingchao Jin", "Hua Zhang"], "journal": "BMC musculoskeletal disorders", "year": 2025, "abstract": "BACKGROUND: There is growing evidence of an association between osteoarthritis (OA) and atherosclerosis (AS). However, their mechanisms are not yet fully understood. The aim of this study was to investigate the common genetic and molecular mechanisms underlying the common pathogenesis of OA and AS.\nMETHODOLOGY: Gene expression profiles of OA (GSE51588) and AS (GSE100927) were obtained from the Gene Expression Omnibus (GEO) database. After identifying shared differentially expressed genes (DEGs) and hub genes, we performed multifaceted bioinformatics analyses, including functional annotation, co-expression analysis, TF-mRNA and ceRNA regulatory network construction, pharmacogenetic prediction, and receiver operator characteristic (ROC) curve assessment. In addition, the immune infiltration of OA and AS was analyzed and compared based on the ssGSEA algorithm, and the correlation between hub genes and infiltrating immune cells was evaluated in OA and AS, respectively.\nRESULT: A total of 48 up-regulated and 43 down-regulated public DEGs were screened between GSE51588 and GSE100927, and functional enrichment analysis emphasized the important role of immune and inflammatory pathways in OA and AS. After protein-protein interaction (PPI) network construction, a total of 9 hub genes (CCR5, IFIT2, MMP1, CXCL9, RSAD2, IFIH1, TNF, IFIT3, and TBX21) were identified as key genes. Targeting the key genes we identified several molecular drug candidates against OA combined with AS related. Additionally diagnostic efficacy assessment using 9 central genes showed great diagnostic value (area under the curve from 0.710 to 0.973). Immune infiltration study also revealed coordinated changes in immune cell profiles in OA and AS diseases.\nCONCLUSION: After a series of bioinformatics analysis and validation, CCR5, IFIT2, MMP1, CXCL9, RSAD2, IFIH1, TNF, IFIT3 and TBX21 were identified as common hub genes for the development of OA and AS. This study provides a new perspective on the common molecular mechanisms between OA and AS, and offers new insights into the potential pathogenesis of OA combined with AS and the direction of treatment.", "claims": [{"id": "claim-method", "statement": "ROC curve analysis was performed using the “pROC” package of the R software and the results were visualized using the “ggplot2” package.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40335993", "locator": "sections[11] \"Diagnostic performance analysis of hub genes\" paragraph 2", "quote": "ROC curve analysis was performed using the “pROC” package of the R software and the results were visualized using the “ggplot2” package."}], "state": "complete"}, {"id": "claim-data-access", "statement": "No datasets were generated or analysed during the current study.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40335993", "locator": "sections[29] \"Data availability\" paragraph 2", "quote": "No datasets were generated or analysed during the current study."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Additionally diagnostic efficacy assessment using 9 central genes showed great diagnostic value (area under the curve from 0.710 to 0.973).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40335993", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Additionally diagnostic efficacy assessment using 9 central genes showed great diagnostic value (area under the curve from 0.710 to 0.973)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Additionally diagnostic efficacy assessment using 9 central genes showed great diagnostic value (area under the curve from 0.710 to 0.973).", "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:40335993"], "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:GSE100927"], "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:GSE100927"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40335993", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12891-025-08563-6", "sha256": "sha256:2dcf6ad66e31a11c8646594c64698200269e3b4f8097e6eabac77960c21363da", "bytes": 48382, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12891-025-08563-6", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12057041", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE100927", "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=GSE100927", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE100927", "version": null, "note": "No datasets were generated or analysed during the current study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "No datasets were generated or analysed during the current study.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM2696609", "GSM2696610", "GSM2696611", "GSM2696612", "GSM2696613", "GSM2696614", "GSM2696615", "GSM2696616", "GSM2696617", "GSM2696618", "GSM2696619", "GSM2696620", "GSM2696621", "GSM2696622", "GSM2696623", "GSM2696624", "GSM2696625", "GSM2696626", "GSM2696627", "GSM2696628", "GSM2696629", "GSM2696630", "GSM2696631", "GSM2696632", "GSM2696633", "GSM2696634", "GSM2696635", "GSM2696636", "GSM2696637", "GSM2696638", "GSM2696639", "GSM2696640", "GSM2696641", "GSM2696642", "GSM2696643", "GSM2696644", "GSM2696645", "GSM2696646", "GSM2696647", "GSM2696648", "GSM2696649", "GSM2696650", "GSM2696651", "GSM2696652", "GSM2696653", "GSM2696654", "GSM2696655", "GSM2696656", "GSM2696657", "GSM2696658", "GSM2696659", "GSM2696660", "GSM2696661", "GSM2696662", "GSM2696663", "GSM2696664", "GSM2696665", "GSM2696666", "GSM2696667", "GSM2696668", "GSM2696669", "GSM2696670", "GSM2696671", "GSM2696672", "GSM2696673", "GSM2696674", "GSM2696675", "GSM2696676", "GSM2696677", "GSM2696678", "GSM2696679", "GSM2696680", "GSM2696681", "GSM2696682", "GSM2696683", "GSM2696684", "GSM2696685", "GSM2696686", "GSM2696687", "GSM2696688", "GSM2696689", "GSM2696690", "GSM2696691", "GSM2696692", "GSM2696693", "GSM2696694", "GSM2696695", "GSM2696696", "GSM2696697", "GSM2696698", "GSM2696699", "GSM2696700", "GSM2696701", "GSM2696702", "GSM2696703", "GSM2696704", "GSM2696705", "GSM2696706", "GSM2696707", "GSM2696708", "GSM2696709", "GSM2696710", "GSM2696711", "GSM2696712"], "sample_count": 104, "group_sizes": null, "group_sizes_basis": null, "platform": "17077", "taxon": "Homo sapiens", "title": "Atherosclerotic and control peripheral artery gene expression", "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": "No datasets were generated or analysed during the current study.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "No datasets were generated or analysed during the current study.", "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}}], "gaps": ["asset:data:geo:GSE100927 not downloaded", "asset:data:geo:GSE100927 licence not read", "asset:data:geo:GSE51588 not downloaded", "asset:data:geo:GSE51588 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": 0.8, "band": "high", "quote": "pathway enrichment"}}, {"id": "method-3", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-4", "family": null, "specific": null, "label": "receiver operator characteristic (ROC) curve analysis using the pROC package", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "ROC curve analysis was performed using the “pROC” package of the R software and the results were visualized using the “ggplot2” package."}}], "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": ["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": ["GSE51588", "GSE100927"], "resolved_accessions": ["GSE51588", "GSE100927"], "statements": ["No datasets were generated or analysed during the current study."], "basis": "The paper names GSE51588, GSE100927 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:40335993", "data:geo:GSE100927"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE100927"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:52:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 13371, "completion_tokens": 1362, "cached_tokens": 0}}, "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:40335993", "type": "paper", "label": "pmid:40335993"}, {"id": "source:pmid:40335993", "type": "manuscript", "label": "PMID 40335993 full text"}, {"id": "data:geo:GSE100927", "type": "dataset", "label": "GEO GSE100927"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40335993", "type": "paper", "label": "pmid:40335993"}, {"id": "source:pmid:40335993", "type": "manuscript", "label": "PMID 40335993 full text"}, {"id": "data:geo:GSE100927", "type": "dataset", "label": "GEO GSE100927"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40335993", "type": "extraction", "used": ["source:pmid:40335993"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE100927", "type": "accession_resolution", "used": ["data:geo:GSE100927"], "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:40335993", "parent_hash": "sha256:d4d270f372992cb4b9715ded6ef3f9675ae0a8604aa04854897c457e9ac266d3", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE100927 licence not read", "asset:data:geo:GSE100927 not downloaded", "asset:data:geo:GSE51588 licence not read", "asset:data:geo:GSE51588 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "mass_spectrometry", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["ded list of similar genes using genomics and proteomics data identification functions. Enrichment an"], "order_basis": "paper_text_order:3989", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.69, "evidence": ["sorption, NF − kappa B signaling pathway and Apoptosis, etc. The results suggest that the common di"], "order_basis": "paper_text_order:7242", "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"}]}