Identification of basement membrane-associated genes as biomarkers for atrial fibrillation.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:41189215", "kind": "science-record", "revision": 3, "content_hash": "sha256:a9b3f597ebea58455a700d848f878b011729628f37d6d6066dcf5063a4ea3da5", "created_at": "2026-11-01T20:31:13Z", "updated_at": "2026-11-01T22:14:55Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of basement membrane-associated genes as biomarkers for atrial fibrillation.", "doi": "10.1097/MD.0000000000045209", "pmid": "41189215", "authors": ["Luofei Huang", "Min Huang", "Han Li", "Jian Shi"], "journal": "Medicine", "year": 2025, "abstract": "Atrial fibrillation (AF) is the most common persistent arrhythmia, contributing substantially to morbidity, mortality, and healthcare burden. The basement membrane is essential for tissue homeostasis and disease regulation. Exploring the relationship between AF and basement membrane-associated genes may provide new insights into the molecular mechanisms of atrial remodeling and arrhythmogenesis. mRNA expression datasets (GSE31821, GSE41177, GSE79768) were obtained from the Gene Expression Omnibus (GEO). The \"merge\" function in R was used to identify the overlap between basement membrane-related genes and these datasets. Differentially expressed basement membrane-related genes (DEBMRGs) were analyzed through enrichment analysis. Key target genes were screened using Lasso regression, Random Forest, SVM-RFE, and protein-protein interaction (PPI) network analysis. Mendelian randomization (MR) was applied for validation. Immune cell infiltration and gene set variation analysis (GSVA) were further performed. Fifty-five DEBMRGs were identified. PPI network construction and machine learning approaches consistently highlighted ITGA1 and ITGB5 as central genes. MR analysis supported these findings, showing an odds ratio (OR) of 1.033 [95% CI: 1.028-1.038, P = 1.55 × 10-36] for ITGA1 and an OR of 0.891 [95% CI: 0.862-0.921, P = 7.66 × 10-12] for ITGB5. No evidence of heterogeneity or pleiotropy was detected. Immune infiltration analysis revealed significant immune cell differences between AF and control samples. This study identifies ITGA1 and ITGB5 as basement membrane-associated genes linked to AF, providing novel insight into AF pathogenesis. These genes may represent promising biomarkers and therapeutic targets for AF management.", "claims": [{"id": "claim-method", "statement": "Following the selection and harmonization of instrumental variables (IVs), 2 DEBMRGs-associated target genes, ITGA1 and ITGB5, were identified as having a causal relationship with AF. IVW analysis showed ITGA1 (OR = 1.033, 95% CI: 1.028–1.038, P = 1.55E-36) and ITGB5 (OR = 0.891, 95% CI: 0.862–0.921, P = 7.66E-12) (Fig. 7).", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41189215", "locator": "sections[20] \"3.6. Mendelian randomization validation of target genes\" paragraph 2", "quote": "Following the selection and harmonization of instrumental variables (IVs), 2 DEBMRGs-associated target genes, ITGA1 and ITGB5, were identified as having a causal relationship with AF. IVW analysis showed ITGA1 (OR = 1.033, 95% CI: 1.028–1.038, P = 1.55E-36) and ITGB5 (OR = 0.891, 95% CI: 0.862–0.921, P = 7.66E-12) (Fig. 7)."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets generated during and/or analyzed during the current study are publicly available.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:41189215", "locator": "sections[33] \"(untitled)\" paragraph 1", "quote": "The datasets generated during and/or analyzed during the current study are publicly available."}], "state": "complete"}, {"id": "claim-target-result", "statement": "MR analysis identified ITGA1 and ITGB5 as showing causal relationships with AF, with ITGA1 associated with increased odds of AF and ITGB5 associated with decreased odds.", "kind": "quantitative", "target": {"value": 95.0, "unit": "per cent", "tolerance": null, "source": "MR analysis supported these findings, showing an odds ratio (OR) of 1.033 [95% CI: 1.028–1.038, P = 1.55 × 10−36] for ITGA1 and an OR of 0.891 [95% CI: 0.862–0.921, P = 7.66 × 10−12] for ITGB5."}, "evidence": [{"asset": "source:pmid:41189215", "locator": "sections[0] \"Abstract\" paragraph 1", "quote": "MR analysis supported these findings, showing an odds ratio (OR) of 1.033 [95% CI: 1.028–1.038, P = 1.55 × 10−36] for ITGA1 and an OR of 0.891 [95% CI: 0.862–0.921, P = 7.66 × 10−12] for ITGB5."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "MR analysis identified ITGA1 and ITGB5 as showing causal relationships with AF, with ITGA1 associated with increased odds of AF and ITGB5 associated with decreased odds.", "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:41189215"], "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:GSE2240"], "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:GSE2240"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:41189215", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1097/MD.0000000000045209", "sha256": "sha256:002204c3e0f5a8c01547a64d5fc1e2a23d4b7972b808a9ff144bb2e5e5542bd9", "bytes": 46272, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1097/MD.0000000000045209", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC12537114", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE2240", "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=GSE2240", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE2240", "version": null, "note": "The datasets generated during and/or analyzed during the current study are publicly available.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are publicly available.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM40980", "GSM40981", "GSM40982", "GSM40983", "GSM40984", "GSM40985", "GSM40986", "GSM40987", "GSM40988", "GSM40989", "GSM40990", "GSM40991", "GSM40992", "GSM40993", "GSM40994", "GSM40995", "GSM40996", "GSM40997", "GSM40998", "GSM40999", "GSM41000", "GSM41001", "GSM41002", "GSM41003", "GSM41004", "GSM41005", "GSM41006", "GSM41007", "GSM41008", "GSM41009", "GSM41010", "GSM41011", "GSM41012", "GSM41013", "GSM41014", "GSM41085", "GSM41086", "GSM41087", "GSM41088", "GSM41089", "GSM41090", "GSM41091", "GSM41092", "GSM41093", "GSM41094", "GSM41095", "GSM41096", "GSM41097", "GSM41098", "GSM41099", "GSM41100", "GSM41101", "GSM41102", "GSM41103", "GSM41104", "GSM41105", "GSM41106", "GSM41107", "GSM41108", "GSM41109", "GSM41110", "GSM41111", "GSM41112", "GSM41113", "GSM41114", "GSM41115", "GSM41116", "GSM41117", "GSM41118", "GSM41119"], "sample_count": 70, "group_sizes": null, "group_sizes_basis": null, "platform": "96;97", "taxon": "Homo sapiens", "title": "Comparison of atrial tissue of patients with atrial fibrillation and sinus rhythm with ventricular gene expression", "resolution_checked_at": "2026-11-01T15:14:33Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE31821", "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=GSE31821", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE31821", "version": null, "note": "The datasets generated during and/or analyzed during the current study are publicly available.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are publicly available.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM789270", "GSM789271", "GSM789272", "GSM789273", "GSM789274", "GSM789275"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene expression and miRNA profiles in atrial fibrillation. Role of miR-21.", "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:GSE41177", "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=GSE41177", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE41177", "version": null, "note": "The datasets generated during and/or analyzed during the current study are publicly available.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets generated during and/or analyzed during the current study are publicly available.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1005418", "GSM1005419", "GSM1005420", "GSM1005421", "GSM1005422", "GSM1005423", "GSM1005424", "GSM1005425", "GSM1005426", "GSM1005427", "GSM1005428", "GSM1005429", "GSM1005430", "GSM1005431", "GSM1005432", "GSM1005433", "GSM1005434", "GSM1005435", "GSM1005436", "GSM1005437", "GSM1005438", "GSM1005439", "GSM1005440", "GSM1005441", "GSM1005442", "GSM1005443", "GSM1005444", "GSM1005445", "GSM1006245", "GSM1006246", "GSM1006247", "GSM1006248", "GSM1006249", "GSM1006250", "GSM1006251", "GSM1006252", "GSM1006253", "GSM1006254"], "sample_count": 38, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Region-specific gene expression profiles in left atria of patients with valvular atrial fibrillation", "resolution_checked_at": "2026-11-01T15:39:54Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}], "gaps": ["asset:data:geo:GSE2240 not downloaded", "asset:data:geo:GSE2240 licence not read", "asset:data:geo:GSE31821 not downloaded", "asset:data:geo:GSE31821 licence not read", "asset:data:geo:GSE41177 not downloaded", "asset:data:geo:GSE41177 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "genetic_association", "specific": "mendelian_randomisation", "label": "Genetic association (GWAS / linkage / MR)", "dsl_operations": ["mr_estimate"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["genotype_phenotype_table"], "evidence": {"score": 1.0, "band": "verbatim", "quote": "Following the selection and harmonization of instrumental variables (IVs), 2 DEBMRGs-associated target genes, ITGA1 and ITGB5, were identified as having a causal relationship with AF. IVW analysis showed ITGA1 (OR = 1.033, 95% CI: 1.028–1.038, P = 1.55E-36) and ITGB5 (OR = 0.891, 95% CI: 0.862–0.921, P = 7.66E-12) (Fig. 7)."}}, {"id": "method-2", "family": "machine_learning", "specific": "random_forest", "label": "Machine learning", "dsl_operations": [], "missing_operations": ["machine_learning_random_forest"], "expressible": false, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "Random Forest"}}, {"id": "method-3", "family": "machine_learning", "specific": "support_vector_machine", "label": "Machine learning", "dsl_operations": ["train_classifier", "cross_validate", "roc_auc"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["labelled_feature_matrix"], "evidence": {"score": 0.7, "band": "medium", "quote": "SVM"}}, {"id": "method-4", "family": "correlation_analysis", "specific": "pearson", "label": "Correlation analysis", "dsl_operations": ["pearson_r"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["paired_numeric_columns"], "evidence": {"score": 0.8, "band": "high", "quote": "Pearson correlation"}}, {"id": "method-5", "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-6", "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": 0.8, "band": "high", "quote": "pathway enrichment"}}], "targets": [{"id": "target-published-estimate", "claim_id": "claim-target-result", "operation": "build_graph", "expected_value": 95.0, "unit": "per cent", "tolerance": null, "state": "complete", "note": "The published estimate as the reader quoted it from the paper. 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