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pmid:38414629

Bioinformatics Analysis and Experimental Validation of Mitochondrial Autophagy Genes in Knee Osteoarthritis.

Kuihan Tang · Li Sun · Long Chen · Xiaobo Feng · Jiarui Wu · Hao Guo · Yong Zheng

International journal of general medicine · 2024 doi:10.2147/IJGM.S444847

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Experiment

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Data

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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pmid:38414629
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2026-11-01T19:20:21Z
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2026-11-01T22:53:46Z
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title
Bioinformatics Analysis and Experimental Validation of Mitochondrial Autophagy Genes in Knee Osteoarthritis.
doi
10.2147/IJGM.S444847
pmid
38414629
authors array · 7 items
[0]
Kuihan Tang
[1]
Li Sun
[2]
Long Chen
[3]
Xiaobo Feng
[4]
Jiarui Wu
[5]
Hao Guo
[6]
Yong Zheng
journal
International journal of general medicine
year
2024
abstract
Background: Mitochondrial autophagy is closely related to the pathogenesis of osteoarthritis, In order to explore the role of mitochondrial autophagy related genes in knee osteoarthritis (KOA) and its molecular mechanism. Methods: KOA-related transcriptome data were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR. Results: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis. Conclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.
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In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5.
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sections[4] "Differential Expression Analysis" paragraph 2
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In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5.
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sections[21] "Data Sharing Statement" paragraph 2
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The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).
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A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).
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sections[11] "Identification of DEMGs" paragraph 2
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A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).
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A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).
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Identification of transcription factors responsible for dysregulated networks in human osteoarthritis cartilage by global gene expression analysis
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Genome-wide Expression Profiles of Subchondral Bone in Osteoarthritis
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In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5.
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inally, biomarker expression was verified by qPCR. Results: A total of 15 DEMGs were obtained
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M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNI
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differential_expression_fit
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fdr_bh
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source_hashes object · 1 field
dsl_catalogue
f2132e96ae6c7a4e
evidence array · 1 item
[0]
In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5.
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Complete file
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Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR.\nResults: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis.\nConclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.", "claims": [{"id": "claim-method", "statement": "In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38414629", "locator": "sections[4] \"Differential Expression Analysis\" paragraph 2", "quote": "In the GSE114007 dataset, differentially expressed genes (DEGs) between KOA samples and normal samples were detected utilizing the “DESeq2” R package (version 1.34.0) with an adjusted p<0.05 and a |log2FC|>0.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:38414629", "locator": "sections[21] \"Data Sharing Statement\" paragraph 2", "quote": "The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:38414629", "locator": "sections[11] \"Identification of DEMGs\" paragraph 2", "quote": "A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 4279 DEGs, including 1969 down-regulated and 2310 up-regulated in KOA samples, were identified (Figure 1a and b).", "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:38414629"], "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:GSE114007"], "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:GSE114007"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:38414629", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.2147/IJGM.S444847", "sha256": 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(https://www.ncbi.nlm.nih.gov/geo/).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3130531", "GSM3130532", "GSM3130533", "GSM3130534", "GSM3130535", "GSM3130536", "GSM3130537", "GSM3130538", "GSM3130539", "GSM3130540", "GSM3130541", "GSM3130542", "GSM3130543", "GSM3130544", "GSM3130545", "GSM3130546", "GSM3130547", "GSM3130548", "GSM3130549", "GSM3130550", "GSM3130551", "GSM3130552", "GSM3130553", "GSM3130554", "GSM3130555", "GSM3130556", "GSM3130557", "GSM3130558", "GSM3130559", "GSM3130560", "GSM3130561", "GSM3130562", "GSM3130563", "GSM3130564", "GSM3130565", "GSM3130566", "GSM3130567", "GSM3130568"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, 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"access_statement_verbatim": "The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM5176138", "GSM5176139", "GSM5176140", "GSM5176141", "GSM5176142", "GSM5176143", "GSM5176144", "GSM5176145", "GSM5176146", "GSM5176147", "GSM5176148"], "sample_count": 11, "group_sizes": null, "group_sizes_basis": null, "platform": "96", "taxon": "Homo sapiens", "title": "Dysregulated gene expression in human osteoarthritis cartilage", "resolution_checked_at": "2026-11-01T19:09:46Z", "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, 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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", "GSE169077", "GSE51588"], "resolved_accessions": ["GSE114007", "GSE169077", "GSE51588"], "statements": ["The GSE114007, GSE169077 and GSE51588 datasets analyzed in this study were collected from the Gene Expression Omnibus (GEO) database (https://www.ncbi.nlm.nih.gov/geo/)."], "basis": "The paper names GSE114007, GSE169077, GSE51588 in Gene Expression Omnibus (GEO) database 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:38414629", "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": "2026-11-01T19:10:21Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11957, "completion_tokens": 2085, "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:38414629", "type": "paper", "label": "pmid:38414629"}, {"id": "source:pmid:38414629", "type": "manuscript", "label": "PMID 38414629 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:38414629", "type": "paper", "label": "pmid:38414629"}, {"id": "source:pmid:38414629", "type": "manuscript", "label": "PMID 38414629 full text"}, {"id": "data:geo:GSE114007", "type": "dataset", "label": "GEO GSE114007"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-38414629", "type": "extraction", "used": ["source:pmid:38414629"], "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:38414629", "parent_hash": "sha256:a3d976b4eb86e15ed529964d7a55412255e330926a57ddbb7f3ba5070c434fb9", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE114007 licence not read", "asset:data:geo:GSE114007 not downloaded", "asset:data:geo:GSE169077 licence not read", "asset:data:geo:GSE169077 not downloaded", "asset:data:geo:GSE51588 licence not read", "asset:data:geo:GSE51588 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "qpcr", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["inally, biomarker expression was verified by qPCR. 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