Identification of key genes and pathways in calcific aortic valve disease by bioinformatics analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:32030260", "kind": "science-record", "revision": 4, "content_hash": "sha256:c583585b8c491702fb737f83f8c8430d45449e85d53ac8eda722561bc6fe67ce", "created_at": "2026-11-01T17:33:22Z", "updated_at": "2026-11-01T22:01:16Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of key genes and pathways in calcific aortic valve disease by bioinformatics analysis.", "doi": "10.21037/jtd.2019.11.57", "pmid": "32030260", "authors": ["Yiran Zhang", "Liang Ma"], "journal": "Journal of thoracic disease", "year": 2019, "abstract": "BACKGROUND: Calcific aortic valve disease (CAVD) is the most common type of valvular heart disease in the elderly. This study is aimed to explore molecular mechanism of CAVD via bioinformatics analysis.\nMETHODS: The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using the MetaDE package in R software. Functional and pathway enrichment analysis were performed based on Gene ontology (GO) and KEGG pathway database. Then, STRING database, Cytoscape and MCODE were applied to construct the protein-protein interaction (PPI) network and screen hub genes. Pathway enrichment analysis was further performed for hub genes and gene clusters identified via module analysis.\nRESULTS: A total of 107 DEGs were identified in CAVD (53 up-regulated genes, and 54 down-regulated genes), and they were mainly enriched in the terms of immune response, extracellular matrix organization, leukocyte transendothelial migration, cell adhesion molecules (CAMs), and fatty acid metabolism. Five hub genes including VCAM1, MMP9, ITGB2, RAC2, and vWF were identified via PPI network, which were mainly enriched in terms of leukocyte transendothelial migration and cell adhesion. An independently down-regulated protein cluster containing ALDH2, HIBCH, ACADVL, ECHDC2, VAT1L, and MAOA was also identified via PPI network.\nCONCLUSIONS: The present study identified VCAM1, MMP9, ITGB2, RAC2, vWF and ALDH2 as key genes in the progression of CAVD. Immune cells infiltration might play a key role in the progression of CAVD, while ALDH2-mediated detoxification effect might play a protective role in CAVD. Further studies are needed to elucidate the pathogenesis of CAVD.", "claims": [{"id": "claim-method", "statement": "Differentially expressed genes (DEGs) were screened using the MetaDE package in R software.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32030260", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "Differentially expressed genes (DEGs) were screened using the MetaDE package in R software."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:32030260", "locator": "sections[0] \"Abstract\" paragraph 2", "quote": "The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified VCAM1, MMP9, ITGB2, RAC2, vWF and ALDH2 as key genes in the progression of CAVD.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:32030260", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The present study identified VCAM1, MMP9, ITGB2, RAC2, vWF and ALDH2 as key genes in the progression of CAVD."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The study identified VCAM1, MMP9, ITGB2, RAC2, vWF and ALDH2 as key genes in the progression of CAVD.", "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:32030260"], "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:GSE51472"], "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:GSE51472"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:32030260", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.21037/jtd.2019.11.57", "sha256": "sha256:25c7eb4578adb4fcead63ec075a395b7fb96f62cc8bed4a26e6cb1c6d26f82d1", "bytes": 1860, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.21037/jtd.2019.11.57", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6988017", "source": "ncbi_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"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 gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database.", "access_statement_kind": "repository_route_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}}, {"id": "data:geo:GSE83453", "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=GSE83453", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE83453", "version": null, "note": "The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2203485", "GSM2203486", "GSM2203487", "GSM2203488", "GSM2203489", "GSM2203490", "GSM2203491", "GSM2203492", "GSM2203493", "GSM2203494", "GSM2203495", "GSM2203496", "GSM2203497", "GSM2203498", "GSM2203499", "GSM2203500", "GSM2203501", "GSM2203502", "GSM2203503", "GSM2203504", "GSM2203505", "GSM2203506", "GSM2203507", "GSM2203508", "GSM2203509", "GSM2203510", "GSM2203511"], "sample_count": 27, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression profile of calcified bicuspid, tricuspid and normal human aortic valves", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE51472 not downloaded", "asset:data:geo:GSE51472 licence not read", "asset:data:geo:GSE83453 not downloaded", "asset:data:geo:GSE83453 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": 0.7, "band": "medium", "quote": "pathway enrichment"}}, {"id": "method-3", "family": null, "specific": null, "label": "MetaDE package in R software", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Differentially expressed genes (DEGs) were screened using the MetaDE package in R software."}}], "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": ["GSE51472", "GSE83453"], "resolved_accessions": ["GSE51472", "GSE83453"], "statements": ["The gene expression profiles of GSE51472 (including 5 normal aortic valve and 5 calcified aortic valve) and GSE83453 (including 8 normal aortic valve and 19 calcified aortic valve) were downloaded from the Gene Expression Omnibus (GEO) database."], "basis": "The paper names GSE51472, GSE83453 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": ["build_graph", "centrality_scores", "pathway_enrich"], "assets": ["source:pmid:32030260", "data:geo:GSE51472"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE51472"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T16:59:20Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": null}, "calls": 5, "usage": {"prompt_tokens": 2046, "completion_tokens": 987, "cached_tokens": 188}}, "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:32030260", "type": "paper", "label": "pmid:32030260"}, {"id": "source:pmid:32030260", "type": "manuscript", "label": "PMID 32030260 full text"}, {"id": "data:geo:GSE51472", "type": "dataset", "label": "GEO GSE51472"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:32030260", "type": "paper", "label": "pmid:32030260"}, {"id": "source:pmid:32030260", "type": "manuscript", "label": "PMID 32030260 full text"}, {"id": "data:geo:GSE51472", "type": "dataset", "label": "GEO GSE51472"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-32030260", "type": "extraction", "used": ["source:pmid:32030260"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE51472", "type": "accession_resolution", "used": ["data:geo:GSE51472"], "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:32030260", "parent_hash": "sha256:3412a8d68a51aa9f0fdb15731117fa8a7b8067e662c7857a288a4688fbde0953", "fork_of": null, "generation": 3}, "gaps": ["asset:data:geo:GSE51472 licence not read", "asset:data:geo:GSE51472 not downloaded", "asset:data:geo:GSE83453 licence not read", "asset:data:geo:GSE83453 not downloaded", "execution.not_run", "method.reader_named_unmapped", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": "analysis_only", "id": "assay:1"}]}