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pmid:37283761
Identification of 3 key genes as novel diagnostic and therapeutic targets for OA and COVID-19.
Yiwei Zhang · Zhengwei Duan · Yonghao Guan · Tianyang Xu · Yuesong Fu · Guodong Li
Frontiers in immunology · 2023 doi:10.3389/fimmu.2023.1167639
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Experiment
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Data
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Analysis
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Execution
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Complete file
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However, the association between COVID-19 and osteoarthritis at the genetic level has not been investigated. This study is intended to analyze the pathogenesis shared by OA and COVID-19 and to identify drugs that could be used to treat SARS-CoV-2-infected OA patients.\nMethods: The four datasets of OA and COVID-19 (GSE114007, GSE55235, GSE147507, and GSE17111) used for the analysis in this paper were obtained from the GEO database. Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis. Finally, drug prediction and molecular docking were carried out using the Drug Signatures Database (DSigDB) and AutoDockTools.\nResults: Firstly, WGCNA identified a total of 26 genes common between OA and COVID-19, and functional analysis of the common genes revealed the common pathological processes and molecular changes between OA and COVID-19 are mainly related to immune dysfunction. In addition, we screened 3 key genes, DDIT3, MAFF, and PNRC1, and uncovered that key genes are possibly involved in the pathogenesis of OA and COVID-19 through high expression in neutrophils. Finally, we established a regulatory network of common genes between OA and COVID-19, and the free energy of binding estimation was used to identify suitable medicines for the treatment of OA patients infected with SARS-CoV-2.\nConclusion: In the present study, we succeeded in identifying 3 key genes, DDIT3, MAFF, and PNRC1, which are possibly involved in the development of both OA and COVID-19 and have high diagnostic value for OA and COVID-19. In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2.", "claims": [{"id": "claim-method", "statement": "Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. 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In addition, niclosamide, ciclopirox, and ticlopidine were found to be potentially useful for the treatment of OA patients infected with SARS-CoV-2."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified three key genes—DDIT3, MAFF, and PNRC1—and proposed niclosamide, ciclopirox, and ticlopidine as potential therapeutic agents for osteoarthritis patients infected with SARS-CoV-2.", "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:37283761"], "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. 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE114007", "GSE55235", "GSE147507", "GSE171110"], "resolved_accessions": ["GSE114007", "GSE55235", "GSE147507", "GSE171110"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/ Supplementary Material ."], "basis": "The paper names GSE114007, GSE55235, GSE147507, GSE171110 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": ["glm_logit_fit"], "assets": ["source:pmid:37283761", "data:geo:GSE114007"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE114007"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:43:08Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11209, "completion_tokens": 2512, "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:37283761", "type": "paper", "label": "pmid:37283761"}, {"id": "source:pmid:37283761", "type": "manuscript", "label": "PMID 37283761 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37283761", "type": "paper", "label": "pmid:37283761"}, {"id": "source:pmid:37283761", "type": "manuscript", "label": "PMID 37283761 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37283761", "type": "extraction", "used": ["source:pmid:37283761"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE114007", "type": "accession_resolution", "used": ["data:geo:GSE114007"], "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:37283761", "parent_hash": "sha256:277d94c5733aef46d3b8cae89491266d5519599ad0e079c6bd4995856a802bf5", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE114007 licence not read", "asset:data:geo:GSE114007 not downloaded", "asset:data:geo:GSE147507 licence not read", "asset:data:geo:GSE147507 not downloaded", "asset:data:geo:GSE171110 licence not read", "asset:data:geo:GSE171110 not downloaded", "asset:data:geo:GSE55235 licence not read", "asset:data:geo:GSE55235 not downloaded", "execution.not_run", "method.reader_differs_from_extractor", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "scrna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "unsupported", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["e-cell analysis of key genes Utilizing blood single-cell RNA sequencing (scRNA-seq) data of 717 COVID-19 patients fr", "nesinglecell.org/) that contains whole blood scRNA-seq data from 717 COVID-19 patients was performe", "Utilizing blood single-cell RNA sequencing (scRNA-seq) data of 717 COVID-19 patients from the DISC"], "order_basis": "paper_text_order:3415", "id": "assay:1"}, {"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["sis of key genes Utilizing blood single-cell RNA sequencing (scRNA-seq) data of 717 COVID-19 patients fr"], "order_basis": "paper_text_order:7050", "id": "assay:2"}, {"role": "analysis", "definition_id": "regression_modelling", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["glm_logit_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 1.0, "evidence": ["Common genes of OA and COVID-19 were identified through Weighted Gene Co-Expression Network Analysis (WGCNA) and differential gene expression analysis. The least absolute shrinkage and selection operator (LASSO) algorithm was used to screen key genes, which were analyzed for expression patterns by single-cell analysis."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}