Comprehensive bioinformatics analysis of hub genes in ischemic heart failure and atrial fibrillation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:40066352", "kind": "science-record", "revision": 4, "content_hash": "sha256:85ac78f47f4181876f332130a295fd1548814f7594a969cae0bce85f26caa78c", "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": "Comprehensive bioinformatics analysis of hub genes in ischemic heart failure and atrial fibrillation.", "doi": "10.3389/fcvm.2025.1499065", "pmid": "40066352", "authors": ["Meimei Zhou", "Youkang Xu", "Lili Zhang", "Yushan Yang", "Jiejiao Zheng"], "journal": "Frontiers in cardiovascular medicine", "year": 2025, "abstract": "Background: Atrial fibrillation (AF) and heart failure (HF) frequently coexist and mutually influence each other. The association between AF and the subtype of HF, Ischaemic heart failure (IHF), remains insufficiently described, despite their high prevalence. Hence, comprehending their underlying pathophysiological mechanisms and identifying new therapeutic targets are urgently needed.\nObjective: This exploration aims to unearth related genes and pathways of IHF and AF, offering new perspectives for their joint diagnosis and treatment.\nMethods: Datasets for HF (GSE57338) and AF (GSE128188) were acquired from the Gene Expression Omnibus (GEO) database. Intersecting these sets generated common differentially expressed genes (DEGs) for further analyses, including Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, protein-protein interaction (PPI), and hub gene identification. Subsequently, the HF dataset (GSE116250) and AF dataset (GSE2240) were utilized to confirm the expression of the hub genes, followed by examination of gene expression patterns across cells in single-cell datasets.\nResults: The study identified 20 common DEGs. Among them, 10 hub genes (SFRP4, FMOD, HAPLN1, LTBP2, SVEP1, BCL6, ANPEP, CD38, ATRNL1, and BEX1) were found to be associated with the co-occurrence of IHF and AF. Enrichment analysis revealed the predominant involvement of these hub genes in extracellular matrix (ECM). Data from the Uniprot database revealed the involvement of the Wnt signaling pathway and TGF-β1/Smads signaling pathway in the development and progression of AF and IHF. Single-cell analysis demonstrated high gene expression primarily in monocytes.\nConclusion: The identified 10 hub genes can serve as potentially valuable biomarkers for IHF and AF. Enrichment analysis reveals that these potential biomarkers are significantly associated with ECM, nicotinate, and nicotinamide metabolism, providing a foundational target for the joint diagnosis and treatment of the two diseases.", "claims": [{"id": "claim-method", "statement": "DEGs were identified using R software (version 4.2.3) with two specialized packages: “limma” (version 3.54.2) and “edgeR” (version 3.40.2). These packages enabled differential expression analyses for RNA-sequencing and microarray studies.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40066352", "locator": "sections[4] \"Identification of DEGs\" paragraph 2", "quote": "DEGs were identified using R software (version 4.2.3) with two specialized packages: “limma” (version 3.54.2) and “edgeR” (version 3.40.2). These packages enabled differential expression analyses for RNA-sequencing and microarray studies."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Publicly available datasets were analyzed in this study. This data can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE57338, GSE116250, GSE128188, GSE2240, GSE267644.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:40066352", "locator": "sections[19] \"Data availability statement\" paragraph 2", "quote": "Publicly available datasets were analyzed in this study. This data can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE57338, GSE116250, GSE128188, GSE2240, GSE267644."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The study identified 20 common DEGs and 10 hub genes associated with the co-occurrence of ischemic heart failure and atrial fibrillation.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:40066352", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "The study identified 20 common DEGs."}, {"asset": "source:pmid:40066352", "locator": "sections[0] \"Abstract\" paragraph 4", "quote": "Among them, 10 hub genes (SFRP4, FMOD, HAPLN1, LTBP2, SVEP1, BCL6, ANPEP, CD38, ATRNL1, and BEX1) were found to be associated with the co-occurrence of IHF and AF."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "partial", "objective": "The study identified 20 common DEGs and 10 hub genes associated with the co-occurrence of ischemic heart failure and atrial fibrillation.", "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:40066352"], "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": "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": [], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": ["step:obtain_source_data blocked on data:accession_absent"]}, "data": {"state": "partial", "assets": [{"id": "source:pmid:40066352", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2025.1499065", "sha256": "sha256:7faa542059ff3c378cf54fbf6ea33333b043755d761f96095755b5e5fe15b0da", "bytes": 30929, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fcvm.2025.1499065", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC11891352", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}], "gaps": []}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "family": "differential_expression", "specific": "edger", "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": "DEGs were identified using R software (version 4.2.3) with two specialized packages: “limma” (version 3.54.2) and “edgeR” (version 3.40.2). These packages enabled differential expression analyses for RNA-sequencing and microarray studies."}}, {"id": "method-2", "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": 0.8, "band": "high", "quote": "limma"}}, {"id": "method-3", "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": "blocked", "tier": "R4", "blocking_axis": "data", "blocked_on": "data:accession_absent", "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: edger."}, "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": ["Publicly available datasets were analyzed in this study. This data can be found in the GEO database (https://www.ncbi.nlm.nih.gov/geo/), accession numbers: GSE57338, GSE116250, GSE128188, GSE2240, GSE267644."], "basis": "The paper names no accession to its source data, so the data has to come from the authors."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:40066352"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "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": "2026-11-01T19:48:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 8668, "completion_tokens": 1959, "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:40066352", "type": "paper", "label": "pmid:40066352"}, {"id": "source:pmid:40066352", "type": "manuscript", "label": "PMID 40066352 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:40066352", "type": "paper", "label": "pmid:40066352"}, {"id": "source:pmid:40066352", "type": "manuscript", "label": "PMID 40066352 full text"}, {"id": "data:geo:None", "type": "dataset", "label": "GEO None"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-40066352", "type": "extraction", "used": ["source:pmid:40066352"], "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:40066352", "parent_hash": "sha256:c8d4437a2221eee3dd7a7f6fd5291cb259aa94b0910ebad150b44be7a6e457d9", "fork_of": null, "generation": 3}, "gaps": ["execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique", "step:obtain_source_data blocked on data:accession_absent"], "assays": [{"role": "data_generation", "definition_id": "rna_seq", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.83, "evidence": ["roenvironment was analyzed using single-cell transcriptomic datasets GSM8271496 and GSM8271498. Single-c", "asets GSM8271496 and GSM8271498. Single-cell transcriptome data preprocessing employed the “Seurat” pac"], "order_basis": "paper_text_order:2246", "id": "assay:1"}, {"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": ["DEGs were identified using R software (version 4.2.3) with two specialized packages: “limma” (version 3.54.2) and “edgeR” (version 3.40.2). These packages enabled differential expression analyses for RNA-sequencing and microarray studies."], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}