Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40063555", "kind": "science-record", "revision": 4, "content_hash": "sha256:2d6482d0fd40d54c82ea2be0f579e54a2efcbd7e0f7a62f6274e53908bdb06fb", "created_at": "2026-11-01T20:30:16Z", "updated_at": "2026-11-01T22:56:12Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Analysis of cellular senescence-related genes in calcified aortic valve disease and the potential therapeutic role of β-Carotene.", "doi": "10.1371/journal.pone.0318574", "pmid": "40063555", "authors": ["Yijing Tao", "Chengjie Gao", "Juan Wang", "Qiyin Zhang", "Zhisong Wang", "Leng Han", "Donglai Cao", "Qianwen Yao"], "journal": "PloS one", "year": 2025, "abstract": "OBJECTIVE: Calcific aortic valve disease (CAVD) is a progressive, age-related degenerative disease characterized by the accumulation of calcium deposits in the aortic valve. We aim to screen key genes associated with cellular senescence (CS) in CAVD.\nMETHODS: The GSE12644 and GSE51472 datasets from the GEO database was utilized in this study, and differentially expressed genes (DEGs) were identified using the \"limma\" R package. CS-related DEGs (CS-DEGs) were determined through the CellAge database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed on CS-DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. The cytoHubba plug-in in Cytoscape was used to identify hub genes. A noncoding-RNA-mRNA regulatory network was established. DSigDB database was used to to identify drugs potentially be useful for treating CAVD.\nRESULTS: A total of 16 CS-DEGs were identified. These genes were primarily associated with collagen metabolic process, collagen catabolic process and external side of plasma membrane. 10 hub genes were identified as regulators of cellular senescence in CAVD: LPAR1, PTPN6, CD28, ID1, MEIS2, FGFR3, KDR, MMP7, AR, HIF1A. The Noncoding RNA-mRNA regulatory network indicated that CS-DEGs may be regulated by noncoding RNAs. β-Carotene, a naturally occurring carotenoid with antioxidant properties, was identified potential therapeutic agents through interacting with MMP9, MEIS2, and CTSB.\nCONCLUSION: This study provides insights into the key genes and pathways related to cellular senescence in CAVD (MMP9, MEIS2, and CTSB) and highlights the potential role of β-Carotene treatment of CAVD.", "claims": [{"id": "claim-method", "statement": "The “limma” R package was also used to analyze the differential expression of mRNAs.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40063555", "locator": "sections[4] \"Data preprocessing\" paragraph 2", "quote": "The “limma” R package was also used to analyze the differential expression of mRNAs."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40063555", "locator": "sections[22] \"Data Availability\" paragraph 2", "quote": "The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472)."}], "state": "complete"}, {"id": "claim-target-result", "statement": "A total of 16 CS-DEGs were identified.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40063555", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "A total of 16 CS-DEGs were identified."}, {"asset": "source:pmid:40063555", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "10 hub genes were identified as regulators of cellular senescence in CAVD: LPAR1, PTPN6, CD28, ID1, MEIS2, FGFR3, KDR, MMP7, AR, HIF1A."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "A total of 16 CS-DEGs were identified.", "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:40063555"], "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:GSE12644"], "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:GSE12644"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40063555", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1371/journal.pone.0318574", "sha256": "sha256:4c80a1f87aa19e317f70985fadaa36c32b267336d3883c7eb8ccadf6a5d4090d", "bytes": 34849, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1371/journal.pone.0318574", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11892872", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE12644", "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=GSE12644", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE12644", "version": null, "note": "The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM317342", "GSM317343", "GSM317344", "GSM317345", "GSM317346", "GSM317347", "GSM317348", "GSM317349", "GSM317350", "GSM317351", "GSM377368", "GSM377369", "GSM377370", "GSM377371", "GSM377372", "GSM377373", "GSM377374", "GSM377375", "GSM377376", "GSM377377"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression profile of normal and calcified stenotic human aortic valves", "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:GSE51472", "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=GSE51472", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE51472", "version": null, "note": "The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472).", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472).", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1246204", "GSM1246205", "GSM1246206", "GSM1246207", "GSM1246208", "GSM1246209", "GSM1246210", "GSM1246211", "GSM1246212", "GSM1246213", "GSM1246214", "GSM1246215", "GSM1246216", "GSM1246217", "GSM1246218"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Expression data of human aortic valve cusps", "resolution_checked_at": "2026-11-01T11:38:18Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE12644 not downloaded", "asset:data:geo:GSE12644 licence not read", "asset:data:geo:GSE51472 not downloaded", "asset:data:geo:GSE51472 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 “limma” R package was also used to analyze the differential expression of mRNAs."}}, {"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"}}], "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": ["GSE12644", "GSE51472"], "resolved_accessions": ["GSE12644", "GSE51472"], "statements": ["The data analyzed in this article comes from Gene Expression Omnibus (GEO) database (http://www.ncbi.nlm.nih.gov/geo). The accession number can be found in the materials and methods section of the article (Or link as: GSE12644: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE12644;GSE51472: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE51472)."], "basis": "The paper names GSE12644, GSE51472 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:40063555", "data:geo:GSE12644"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE12644"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T19:48:06Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 10768, "completion_tokens": 1429, "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:40063555", "type": "paper", "label": "pmid:40063555"}, {"id": "source:pmid:40063555", "type": "manuscript", "label": "PMID 40063555 full text"}, {"id": "data:geo:GSE12644", "type": "dataset", "label": "GEO GSE12644"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40063555", "type": "paper", "label": "pmid:40063555"}, {"id": "source:pmid:40063555", "type": "manuscript", "label": "PMID 40063555 full text"}, {"id": "data:geo:GSE12644", "type": "dataset", "label": "GEO GSE12644"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40063555", "type": "extraction", "used": ["source:pmid:40063555"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE12644", "type": "accession_resolution", "used": ["data:geo:GSE12644"], "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:40063555", "parent_hash": "sha256:016daf881d6116ae4ffb79afa16cf797b55843c2b9945a7bfd0b109a576950e9", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE12644 licence not read", "asset:data:geo:GSE12644 not downloaded", "asset:data:geo:GSE51472 licence not read", "asset:data:geo:GSE51472 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 “limma” R package was also used to analyze the differential expression of mRNAs."], "order_basis": "analysis_only", "id": "assay:1"}]}