Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:30760287", "kind": "science-record", "revision": 8, "content_hash": "sha256:fb93cca404afcd46b5d054b1ec88491e2dfd64cdcb6c86256b3849fc91b40c18", "created_at": "2026-11-01T15:40:42Z", "updated_at": "2026-11-01T22:00:22Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Bioinformatic gene analysis for potential biomarkers and therapeutic targets of atrial fibrillation-related stroke.", "doi": "10.1186/s12967-019-1790-x", "pmid": "30760287", "authors": ["Rongjun Zou", "Dingwen Zhang", "Lei Lv", "Wanting Shi", "Zijiao Song", "Bin Yi", "Bingjia Lai", "Qian Chen", "Songran Yang", "Ping Hua"], "journal": "Journal of translational medicine", "year": 2019, "abstract": "BACKGROUND: Atrial fibrillation (AF) is one of the most prevalent sustained arrhythmias, however, epidemiological data may understate its actual prevalence. Meanwhile, AF is considered to be a major cause of ischemic strokes due to irregular heart-rhythm, coexisting chronic vascular inflammation, and renal insufficiency, and blood stasis. We studied co-expressed genes to understand relationships between atrial fibrillation (AF) and stroke and reveal potential biomarkers and therapeutic targets of AF-related stroke.\nMETHODS: AF-and stroke-related differentially expressed genes (DEGs) were identified via bioinformatic analysis Gene Expression Omnibus (GEO) datasets GSE79768 and GSE58294, respectively. Subsequently, extensive target prediction and network analyses methods were used to assess protein-protein interaction (PPI) networks, Gene Ontology (GO) terms and pathway enrichment for DEGs, and co-expressed DEGs coupled with corresponding predicted miRNAs involved in AF and stroke were assessed as well.\nRESULTS: We identified 489, 265, 518, and 592 DEGs in left atrial specimens and cardioembolic stroke blood samples at < 3, 5, and 24 h, respectively. LRRK2, CALM1, CXCR4, TLR4, CTNNB1, and CXCR2 may be implicated in AF and the hub-genes of CD19, FGF9, SOX9, GNGT1, and NOG may be associated with stroke. Finally, co-expressed DEGs of ZNF566, PDZK1IP1, ZFHX3, and PITX2 coupled with corresponding predicted miRNAs, especially miR-27a-3p, miR-27b-3p, and miR-494-3p may be significantly associated with AF-related stroke.\nCONCLUSION: AF and stroke are related and ZNF566, PDZK1IP1, ZFHX3, and PITX2 genes are significantly associated with novel biomarkers involved in AF-related stroke.", "claims": [{"id": "claim-data-access", "statement": "GSE79768 and GSE58294 datasets were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/) [13] and expression profiling arrays were generated using GPL570 (HG‑U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Additionally, the GSE79768 dataset, including 26 specimens with paired left atrial (LA) and right atrial (RA) tissue obtained from 13 patients was used to identify differential LA-to-RA gene expression and molecular mechanisms for patients with persistent AF or sinus rhythm (SR) abnormalities and we describe potential mechanisms of AF-related remodeling in the LA and the relationship between LA arrhythmogenesis and thrombogenesis.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:30760287", "locator": "sections[3] \"Materials and methods\" paragraph 2", "quote": "GSE79768 and GSE58294 datasets were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/) [13] and expression profiling arrays were generated using GPL570 (HG‑U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Additionally, the GSE79768 dataset, including 26 specimens with paired left atrial (LA) and right atrial (RA) tissue obtained from 13 patients was used to identify differential LA-to-RA gene expression and molecular mechanisms for patients with persistent AF or sinus rhythm (SR) abnormalities and we describe potential mechanisms of AF-related remodeling in the LA and the relationship between LA arrhythmogenesis and thrombogenesis."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": null, "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:30760287"], "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:GSE58294"], "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:GSE58294"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:30760287", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12967-019-1790-x", "sha256": "sha256:60a4609ebdb384b40ae0a618359b00409261ce185c5f2f6c0c0fbed5470547b1", "bytes": 31917, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12967-019-1790-x", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC6375208", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE58294", "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=GSE58294", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE58294", "version": null, "note": "GSE79768 and GSE58294 datasets were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/) [13] and expression profiling arrays were generated using GPL570 (HG‑U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Additionally, the GSE79768 dataset, including 26 specimens with paired left atrial (LA) and right atrial (RA) tissue obtained from 13 patients was used to identify differential LA-to-RA gene expression and molecular mechanisms for patients with persistent AF or sinus rhythm (SR) abnormalities and we describe potential mechanisms of AF-related remodeling in the LA and the relationship between LA arrhythmogenesis and thrombogenesis.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "GSE79768 and GSE58294 datasets were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/) [13] and expression profiling arrays were generated using GPL570 (HG‑U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). 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Additionally, the GSE79768 dataset, including 26 specimens with paired left atrial (LA) and right atrial (RA) tissue obtained from 13 patients was used to identify differential LA-to-RA gene expression and molecular mechanisms for patients with persistent AF or sinus rhythm (SR) abnormalities and we describe potential mechanisms of AF-related remodeling in the LA and the relationship between LA arrhythmogenesis and thrombogenesis.", "access_statement_kind": "repository_route_statement", "sample_accessions": ["GSM2102184", "GSM2102185", "GSM2102186", "GSM2102187", "GSM2102188", "GSM2102189", "GSM2102190", "GSM2102191", "GSM2102192", "GSM2102193", "GSM2102194", "GSM2102195", "GSM2102196", "GSM2102197", "GSM2102198", "GSM2102199", "GSM2102200", "GSM2102201", "GSM2102202", "GSM2102203", "GSM2102204", "GSM2102205", "GSM2102206", "GSM2102207", "GSM2102208", "GSM2102209"], "sample_count": 26, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": 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activity, RNA polymerase II proximal promoter sequence-specific DNA binding", "IC", "GO:0000122/GO:0000978", "GO_REF:0000036"], ["Protein binding", "IPI", "UniProtKB:Q13761", "PMID:20599712"], ["Nucleus", "TAS", "", "PMID:1719379"], ["PITX2", "Transcription regulatory region sequence-specific DNA binding", "IDA", "", "PMID:9685346"], ["Transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding", "IEA", "UniProtKB:Q9R0W1", "GO_REF:0000107"], ["RNA polymerase II transcription coactivator activity", "IDA", "", "PMID:9685346"], ["Branching involved in blood vessel morphogenesis", "IEA", "UniProtKB:P97474", "GO_REF:0000107"], ["Vasculogenesis", "IEA", "UniProtKB:P97474", "GO_REF:0000107"], ["In utero embryonic development", "IEA", "UniProtKB:P97474", "GO_REF:0000107"], ["Neuron migration", "IEA", "UniProtKB:P97474", "GO_REF:0000107"], ["Extraocular skeletal muscle development", "IEA", "UniProtKB:P97474", "GO_REF:0000107"]], "row_count": 21, "column_count": 5, "numeric_cells": 35, "header_rows": 1, "locator": "section[10]/table-wrap[1]#Tab1"}}, {"id": "asset:table:pmid:30760287:2", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:dbd2d7d00a9918fe919d50624298f7156ef1b323ae61ca2e1914e6e5b2e7561e", "bytes": 2630, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[12]/table-wrap[1]#Tab2", "version": null, "note": "The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment among predicted miRNAs and Co-DEGs", "structure": {"pmcid": "PMC6375208", "section_index": 12, "section_title": "Identification of functional and pathway enrichment among predicted miRNAs and Co-DEGs", "row_count": 34, "column_count": 5}, "table": {"label": "Table 2", "caption": "The Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment among predicted miRNAs and Co-DEGs", "rows": [["Genes", "Predicted miRNAs", "Category", "P value"], ["PDZK1IP1", "hsa-miR-1296-5p", "KEGG pathway", "Hypertrophic cardiomyopathy (HCM)", "0.047"], ["hsa-miR-27a-3p", "", "NF-kappa B signaling pathway", "0.022"], ["hsa-miR-27b-3p", "", "Toll-like receptor signaling pathway", "0.017"], ["hsa-miR-6895-5p", "GO terms", "Negative regulation of energy homeostasis", "4E−04"], ["hsa-miR-4725-3p", "", "Calcium ion-dependent exocytosis of neurotransmitter", "0.001"], ["", "", "Neurotransmitter receptor activity", "0.002"], ["", "", "Regulation of leukocyte migration", "0.003"], ["", "", "Smooth muscle hyperplasia", "0.011"], ["", "", "Immunoglobulin mediated immune response", "0.034"], ["ZNF566", "hsa-miR-216b-5p", "KEGG pathway", "Valine, leucine and isoleucine biosynthesis", "0.320"], ["hsa-miR-1277-5p", "", "Cardiac muscle contraction", "0.411"], ["hsa-miR-6783-5p", "GO terms", "Regulation of acute inflammatory response", "0.007"], ["hsa-miR-369-3p", "", "Commissural neuron differentiation in spinal cord", "0.019"], ["hsa-miR-6778-3p", "", "Cardiac vascular smooth muscle cell differentiation", "0.020"], ["", "", "MHC protein binding", "0.035"], ["", "", "ATP-activated inward rectifier potassium channel activity", "0.035"], ["", "", "Mitochondrial translation", "0.041"], ["PITX2", "hsa-miR-377-3p", "KEGG pathway", "TGF-beta signaling pathway", "3.00E − 03"], ["hsa-miR-141-3p", "", "Phosphatidylinositol signaling system", "0.124"], ["hsa-miR-5692b", "GO terms", "Vascular smooth muscle cell differentiation", "0.002"], ["hsa-miR-4789-5p", "", "Cell proliferation involved in outflow tract morphogenesis", "0.002"], ["hsa-miR-494-3p", "", "Cardiac neural crest cell migration involved in outflow tract morphogenesis", "0.002"], ["", "", "Pulmonary myocardium development", "0.002"], ["", "", "Atrial cardiac muscle tissue morphogenesis", "0.002"], ["", "", "Ventricular cardiac muscle cell development", "0.003"], ["", "", "Cardiac muscle cell 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"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": 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The physical bench the paper used is not, so a physical validation cannot be run here."}, "data": {"tier": "R1", "reachable": true, "accessions": ["GSE79768", "GSE58294"], "resolved_accessions": ["GSE79768", "GSE58294"], "statements": ["GSE79768 and GSE58294 datasets were downloaded from GEO (http://www.ncbi.nlm.nih.gov/geo/) [13] and expression profiling arrays were generated using GPL570 (HG‑U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Additionally, the GSE79768 dataset, including 26 specimens with paired left atrial (LA) and right atrial (RA) tissue obtained from 13 patients was used to identify differential LA-to-RA gene expression and molecular mechanisms for patients with persistent AF or sinus rhythm (SR) abnormalities and we describe potential mechanisms of AF-related remodeling in the LA and the relationship between LA arrhythmogenesis and thrombogenesis."], "basis": "The paper names GSE79768, GSE58294 in Gene Expression Omnibus (GEO) 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:30760287", "data:geo:GSE58294", "asset:table:pmid:30760287:1", "asset:table:pmid:30760287:2"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE58294"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:41:43Z", "independence": "single_reader"}, "evidence_check": {"method": null, "availability": null}, "calls": 3, "usage": {"prompt_tokens": 25307, "completion_tokens": 2762, "cached_tokens": 784}}, "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:30760287", "type": "paper", "label": "pmid:30760287"}, {"id": "source:pmid:30760287", "type": "manuscript", "label": "PMID 30760287 full text"}, {"id": "data:geo:GSE58294", "type": "dataset", "label": "GEO GSE58294"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:30760287", "type": "paper", "label": "pmid:30760287"}, {"id": "source:pmid:30760287", "type": "manuscript", "label": "PMID 30760287 full text"}, {"id": "data:geo:GSE58294", "type": "dataset", "label": "GEO GSE58294"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-30760287", "type": "extraction", "used": ["source:pmid:30760287"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE58294", "type": "accession_resolution", "used": ["data:geo:GSE58294"], "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:30760287", "parent_hash": "sha256:eabc1b7a8acc73300e2ba32fe3e4f4e0dc9f6ff3e07f6625e5ff1f10fe6686f4", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE58294 licence not read", "asset:data:geo:GSE58294 not downloaded", "asset:data:geo:GSE79768 licence not read", "asset:data:geo:GSE79768 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"role": "data_generation", "definition_id": "microarray", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.99, "evidence": ["were generated using GPL570 (HG‑U133_Plus_2) Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix", "Affymetrix Human Genome U133 Plus 2.0 Array (Affymetrix, Santa Clara, CA). Additionally, the GSE7976"], "order_basis": "paper_text_order:1976", "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": 0.8, "evidence": ["limma"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}