Bioinformatics analysis of aging-related genes in thoracic aortic aneurysm and dissection.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:37283588", "kind": "science-record", "revision": 3, "content_hash": "sha256:850426bcb3f7aed97444e52e200fbe697667ee90896855345cde2f01717b826c", "created_at": "2026-11-01T19:02:00Z", "updated_at": "2026-11-01T22:09:37Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatics analysis of aging-related genes in thoracic aortic aneurysm and dissection.", "doi": "10.3389/fcvm.2023.1089312", "pmid": "37283588", "authors": ["Hong Wan", "Danlingyi Liu", "Bingqing Liu", "Mengyao Sha", "Wei Xia", "Chang Liu"], "journal": "Frontiers in cardiovascular medicine", "year": 2023, "abstract": "Objective: Thoracic aortic aneurysm and dissection (TAAD) is a cardiovascular disease with a high mortality rate. Aging is an important risk factor for TAAD. This study explored the relationship between aging and TAAD and investigated the underlying mechanisms, which may contribute to the diagnosis and treatment of TAAD.\nMethods: Human aging genes were obtained from the Aging Atlas official website. Various datasets were downloaded from the GEO database:the human TAAD dataset GSE52093 were used for screening differentially expressed genes (DEGs); GSE137869, GSE102397 and GSE153434 were used as validation sets, and GSE9106 was used for diagnostic prediction of receiver operating characteristic (ROC) curves. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Set Enrichment Analysis (GSEA), and protein-protein interaction (PPI) network analysis were used to screen differentially co-expressed genes from human aging genes and TAAD. Using five methods of the cytoHubba plugin in Cytoscape software (Degree, Closeness, EPC, MNC, Radiality), hub genes were identified from the differentially co-expressed genes. Single-cell RNA sequencing was used to verify the expression levels of hubgenes in different cell types of aortic tissue. ROC curves were used to further screen for diagnostic genes.\nResults: A total of 70 differentially co-expressed genes were screened from human aging genes and DEGs in human TAAD dataset GSE52093. GO enrichment analysis revealed that the DEGs played a major role in regulating DNA metabolism and damaged DNA binding. KEGG enrichment analysis revealed enrichment in the longevity regulating pathway, cellular senescence, and HIF-1 signaling pathway. GSEA indicated that the DEGs were concentrated in the cell cycle and aging-related p53 signaling pathway. The five identified hubgenes were MYC, IL6, HIF1A, ESR1, and PTGS2. Single-cell sequencing of the aging rat aorta showed that hubgenes were expressed differently in different types of cells in aortic tissue. Among these five hubgenes, HIF1A and PTGS2 were validated in the aging dataset GSE102397; MYC, HIF1A and ESR1 were validated in the TAAD dataset GSE153434. The combined area under the diagnostic ROC curve (AUC) values for the five hub genes were >0.7 in the testing and training sets of the dataset GSE9106. The combined AUC values of MYC and ESR1 were equal to the combin ed AUC values of the five hub genes.\nConclusion: The HIF-1 signaling pathway may play an important role in TAAD and aging. MYC and ESR1 may have diagnostic value for aging-related TAAD.", "claims": [{"id": "claim-method", "statement": "Using the dataset GSE9106 (testing set and training set), the ROC curve analysis and result visualization of the hubgenes were performed with the “pROC” package and “ggplot2”, respectively.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37283588", "locator": "sections[11] \"Diagnostic prediction of hubgenes\" paragraph 2", "quote": "Using the dataset GSE9106 (testing set and training set), the ROC curve analysis and result visualization of the hubgenes were performed with the “pROC” package and “ggplot2”, respectively."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository can be found in the article.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:37283588", "locator": "sections[24] \"Data availability statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository can be found in the article."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The five hub genes had a combined diagnostic AUC of 0.812 in the testing set and 0.731 in the training set, while the combination of MYC and ESR1 produced an equal AUC.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:37283588", "locator": "sections[20] \"Diagnostic prediction of the hubgenes\" paragraph 2", "quote": "The area under the diagnostic ROC curve (AUC) showed that in the testing set the combined AUC of these five hubgenes was 0.812, while in the training set the combined AUC value was 0.731."}, {"asset": "source:pmid:37283588", "locator": "sections[20] \"Diagnostic prediction of the hubgenes\" paragraph 2", "quote": "A combined ROC with MYC and ESR1 that had individual AUC > 0.7 was then performed and the results were equal to the AUC value of the combined ROC of all five hub genes (Figure 6E)."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The five hub genes had a combined diagnostic AUC of 0.812 in the testing set and 0.731 in the training set, while the combination of MYC and ESR1 produced an equal AUC.", "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:37283588"], "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": "blocked", "blocked_on": "data:accession_absent", "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": [], "outputs": ["the source data with its repository provenance"], "instruments": [], "reagents": []}, {"id": "run_analysis", "order": 3, "name": "Run the published analysis", "kind": "analysis", "state": "blocked", "blocked_on": "method:group_comparison_wilcoxon", "description": "Apply the paper's statistical method to the resolved series and compare the result with the published target.", "duration_hours": null, "parameters": {}, "inputs": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:run_analysis blocked on method:group_comparison_wilcoxon", "step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:37283588", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2023.1089312", "sha256": "sha256:1bef3f701e8022484b46bc9112fa8206960a60901bfb3cc87775da760669789e", "bytes": 39079, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2023.1089312", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC10239936", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "group_comparison", "specific": "wilcoxon", "label": "Group comparison", "dsl_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "expressible": false, "parameters": {}, "data_shapes": ["two_or_more_groups_continuous"], "evidence": {"score": 0.8, "band": "high", "quote": "Wilcoxon"}}, {"id": "method-2", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"id": "method-3", "family": "correlation_analysis", "specific": "spearman", "label": "Correlation analysis", "dsl_operations": ["spearman_rho"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Spearman correlation"}}, {"id": "method-4", "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-5", "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": "GO enrichment"}}, {"id": "method-6", "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": 0.7, "band": "medium", "quote": "ROC curve"}}, {"id": "method-7", "family": null, "specific": null, "label": "receiver operating characteristic (ROC) curve analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Using the dataset GSE9106 (testing set and training set), the ROC curve analysis and result visualization of the hubgenes were performed with the “pROC” package and “ggplot2”, respectively."}}], "targets": [], "gaps": ["method.reader_named_unmapped", "method.group_comparison_wilcoxon"]}, "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "axes": {"method": {"tier": "R1", "expressible": false, "required_operations": [], "missing_operations": ["group_comparison_wilcoxon"], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: wilcoxon."}, "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": "R4", "reachable": false, "accessions": [], "resolved_accessions": [], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository can be found in the article."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": [], "assets": ["source:pmid:37283588"], "steps": []}, "must_build": {"dsl_operations": [{"operation": "group_comparison_wilcoxon", "unlocks_papers": null, "priority": null}], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:None"]}, "gaps": ["data:accession_absent"]}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:42:57Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11834, "completion_tokens": 3072, "cached_tokens": 256}}, "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:37283588", "type": "paper", "label": "pmid:37283588"}, {"id": "source:pmid:37283588", "type": "manuscript", "label": "PMID 37283588 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37283588", "type": "paper", "label": "pmid:37283588"}, {"id": "source:pmid:37283588", "type": "manuscript", "label": "PMID 37283588 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37283588", "type": "extraction", "used": ["source:pmid:37283588"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-None", "type": "accession_resolution", "used": ["data:geo:None"], "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:37283588", "parent_hash": "sha256:0a0daa3ab47bb00b544963c4b113b4239916cc33951446c3c19a9280ca57e217", "fork_of": null, "generation": 2}, "gaps": ["execution.not_run", "method.group_comparison_wilcoxon", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent", "step:run_analysis blocked on method:group_comparison_wilcoxon"], "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": 0.93, "evidence": ["from the differentially co-expressed genes. Single-cell RNA sequencing was used to verify the expression levels of"], "order_basis": "paper_text_order:1187", "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": ["fferentially co-expressed genes. Single-cell RNA sequencing was used to verify the expression levels of"], "order_basis": "paper_text_order:1198", "id": "assay:2"}, {"role": "data_generation", "definition_id": "animal_model", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.642, "evidence": ["d PTGS2. Single-cell sequencing of the aging rat aorta showed that hubgenes were expressed di"], "order_basis": "paper_text_order:1966", "id": "assay:3"}, {"role": "analysis", "definition_id": "group_comparison", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["Wilcoxon"], "order_basis": "consumes_earlier_output", "id": "assay:4"}]}