Comprehensive Analysis of Hub Genes Associated With Competing Endogenous RNA Networks in Stroke Using Bioinformatics Analysis.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:35096003", "kind": "science-record", "revision": 5, "content_hash": "sha256:b00c57e72fff826515b63466cf9e5260ad861b4ed035d0d947d597e6c767eefe", "created_at": "2026-11-01T17:36:49Z", "updated_at": "2026-11-01T22:05:42Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Comprehensive Analysis of Hub Genes Associated With Competing Endogenous RNA Networks in Stroke Using Bioinformatics Analysis.", "doi": "10.3389/fgene.2021.779923", "pmid": "35096003", "authors": ["Xiuqi Chen", "Danhong Wu"], "journal": "Frontiers in genetics", "year": 2021, "abstract": "Background: Acute ischemic stroke (AIS) is the second leading cause of death and the third leading cause of disability worldwide. Long noncoding RNAs (lncRNAs) are promising biomarkers for the early diagnosis of AIS and closely participate in the mechanism of stroke onset. However, studies focusing on lncRNAs functioning as microRNA (miRNA) sponges to regulate the mRNA expression are rare and superficial. Methods: In this study, we systematically analyzed the expression profiles of lncRNA, mRNA (GSE58294), and miRNA (GSE110993) from the GEO database. Gene ontology (GO) analysis was performed to reveal the functions of differentially expressed genes (DEGs), and we used weighted gene co-expression network analysis (WGCNA) to investigate the relationships between clinical features and expression profiles and the co-expression of miRNA and lncRNA. Finally, we constructed a lncRNA-miRNA-mRNA competing endogenous RNA (ceRNA) network with selected DEGs using bioinformatics methods and obtained ROC curves to assess the diagnostic efficacy of differentially expressed lncRNAs (DElncRNAs) and differentially expressed mRNAs (DEmRNAs) in our network. The GSE22255 dataset was used to confirm the diagnostic value of candidate genes. Results: In total, 199 DElncRNAs, 2068 DEmRNAs, and 96 differentially expressed miRNAs were detected. The GO analysis revealed that DEmRNAs primarily participate in neutrophil activation, neutrophil degranulation, vacuolar transport, and lysosomal transport. WGCNA screened out 16 lncRNAs and 195 mRNAs from DEGs, and only eight DElncRNAs maintained an area under the curve higher than 0.9. By investigating the relationships between lncRNAs and mRNAs, a ceRNA network containing three lncRNAs, three miRNAs, and seven mRNAs was constructed. GSE22255 confirmed that RP1-193H18.2 is more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy. Conclusion: The ceRNA network may broaden our understanding of AIS pathology, and the candidate lncRNA from the ceRNA network is assumed to be a promising therapeutic target and diagnostic biomarker for AIS.", "claims": [{"id": "claim-method", "statement": "To assess the diagnostic efficacy of selected DElncRNAs and DEmRNAs, we used the Proc R package to generate the ROC curve.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35096003", "locator": "sections[9] \"Diagnostic ROC Curve\" paragraph 2", "quote": "To assess the diagnostic efficacy of selected DElncRNAs and DEmRNAs, we used the Proc R package to generate the ROC curve."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:35096003", "locator": "sections[20] \"Data Availability Statement\" paragraph 2", "quote": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."}], "state": "complete"}, {"id": "claim-target-result", "statement": "The validation dataset confirmed that RP1-193H18.2 was more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:35096003", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "GSE22255 confirmed that RP1-193H18.2 is more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "The validation dataset confirmed that RP1-193H18.2 was more advantageous for diagnosing stroke, whereas no mRNA showed realistic diagnostic efficacy.", "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:35096003"], "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:GSE110993"], "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:GSE110993"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:35096003", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fgene.2021.779923", "sha256": "sha256:5d124ea0ca10fff9043eb13b0bc3dc5248af14d86b55f99f4e49a10b79874c37", "bytes": 49785, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fgene.2021.779923", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8790239", "source": "europe_pmc_fulltext", "coverage": "whole_body", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE110993", "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=GSE110993", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE110993", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3019808", "GSM3019809", "GSM3019810", "GSM3019811", "GSM3019812", "GSM3019813", "GSM3019814", "GSM3019815", "GSM3019816", "GSM3019817", "GSM3019818", "GSM3019819", "GSM3019820", "GSM3019821", "GSM3019822", "GSM3019823", "GSM3019824", "GSM3019825", "GSM3019826", "GSM3019827", "GSM3019828", "GSM3019829", "GSM3019830", "GSM3019831", "GSM3019832", "GSM3019833", "GSM3019834", "GSM3019835", "GSM3019836", "GSM3019837", "GSM3019838", "GSM3019839", "GSM3019840", "GSM3019841", "GSM3019842", "GSM3019843", "GSM3019844", "GSM3019845", "GSM3019846", "GSM3019847"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "15456", "taxon": "Homo sapiens", "title": "RNA-seq identifies circulating miR-125a-5p, miR-125b-5p and miR-143-3p as potential biomarkers for acute ischemic stroke", "resolution_checked_at": "2026-11-01T18:06:43Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "data:geo:GSE22255", "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=GSE22255", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE22255", "version": null, "note": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM554014", "GSM554015", "GSM554016", "GSM554017", "GSM554018", "GSM554019", "GSM554020", "GSM554021", "GSM554022", "GSM554023", "GSM554024", "GSM554025", "GSM554026", "GSM554027", "GSM554028", "GSM554029", "GSM554030", "GSM554031", "GSM554032", "GSM554033", "GSM554034", "GSM554035", "GSM554036", "GSM554037", "GSM554038", "GSM554039", "GSM554040", "GSM554041", "GSM554042", "GSM554043", "GSM554044", "GSM554045", "GSM554046", "GSM554047", "GSM554048", "GSM554049", "GSM554050", "GSM554051", "GSM554052", "GSM554053"], "sample_count": 40, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Blood genomic expression profile for ischemic stroke (IS)", "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: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": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1406033", "GSM1406034", "GSM1406035", "GSM1406036", "GSM1406037", "GSM1406038", "GSM1406039", "GSM1406040", "GSM1406041", "GSM1406042", "GSM1406043", "GSM1406044", "GSM1406045", "GSM1406046", "GSM1406047", "GSM1406048", "GSM1406049", "GSM1406050", "GSM1406051", "GSM1406052", "GSM1406053", "GSM1406054", "GSM1406055", "GSM1406056", "GSM1406057", "GSM1406058", "GSM1406059", "GSM1406060", "GSM1406061", "GSM1406062", "GSM1406063", "GSM1406064", "GSM1406065", "GSM1406066", "GSM1406067", "GSM1406068", "GSM1406069", "GSM1406070", "GSM1406071", "GSM1406072", "GSM1406073", "GSM1406074", "GSM1406075", "GSM1406076", "GSM1406077", "GSM1406078", "GSM1406079", "GSM1406080", "GSM1406081", "GSM1406082", "GSM1406083", "GSM1406084", "GSM1406085", "GSM1406086", "GSM1406087", "GSM1406088", "GSM1406089", "GSM1406090", "GSM1406091", "GSM1406092", "GSM1406093", "GSM1406094", "GSM1406095", "GSM1406096", "GSM1406097", "GSM1406098", "GSM1406099", "GSM1406100", "GSM1406101", "GSM1406102", "GSM1406103", "GSM1406104", "GSM1406105", "GSM1406106", "GSM1406107", "GSM1406108", "GSM1406109", "GSM1406110", "GSM1406111", "GSM1406112", "GSM1406113", "GSM1406114", "GSM1406115", "GSM1406116", "GSM1406117", "GSM1406118", "GSM1406119", "GSM1406120", "GSM1406121", "GSM1406122", "GSM1406123", "GSM1406124"], "sample_count": 92, "group_sizes": null, "group_sizes_basis": null, "platform": "570", "taxon": "Homo sapiens", "title": "Gene Expression Following Cardioembolic Stroke", "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:GSE110993 not downloaded", "asset:data:geo:GSE110993 licence not read", "asset:data:geo:GSE22255 not downloaded", "asset:data:geo:GSE22255 licence not read", "asset:data:geo:GSE58294 not downloaded", "asset:data:geo:GSE58294 licence not read"]}, "analysis": {"state": "partial", "methods": [{"id": "method-1", "family": "principal_component_analysis", "specific": "pca", "label": "Principal component analysis", "dsl_operations": ["pca_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["wide_numeric_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "principal component analysis"}}, {"id": "method-2", "family": "clustering", "specific": "hierarchical", "label": "Clustering", "dsl_operations": ["hierarchical_cluster"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["feature_matrix"], "evidence": {"score": 0.8, "band": "high", "quote": "dendrogram"}}, {"id": "method-3", "family": "diagnostic_evaluation", "specific": "roc", "label": "Diagnostic test evaluation", "dsl_operations": ["confusion_counts", "roc_curve", "sensitivity_specificity", "solve_confusion_matrix", "classification_metrics", "published_precision_envelope"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["reference_standard_and_test"], "evidence": {"score": 0.8, "band": "high", "quote": "ROC curve"}}, {"id": "method-4", "family": null, "specific": null, "label": "Receiver operating characteristic (ROC) curve analysis", "dsl_operations": [], "missing_operations": [], "expressible": null, "parameters": {}, "data_shapes": [], "evidence": {"score": 1.0, "band": "verbatim", "quote": "To assess the diagnostic efficacy of selected DElncRNAs and DEmRNAs, we used the Proc R package to generate the ROC curve."}}], "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": ["pca_fit"], "missing_operations": [], "basis": "The paper names the method it used and the corpus's method extractor maps it onto the DSL catalogue: pca."}, "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": ["GSE58294", "GSE110993", "GSE22255"], "resolved_accessions": ["GSE58294", "GSE110993", "GSE22255"], "statements": ["The datasets presented in this study can be found in online repositories. The names of the repository/repositories and accession number(s) can be found in the article/Supplementary Material."], "basis": "The paper names GSE58294, GSE110993, GSE22255 in GEO database and the accession resolves in the repository. No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["pca_fit"], "assets": ["source:pmid:35096003", "data:geo:GSE110993"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE110993"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T17:31:18Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 15547, "completion_tokens": 1415, "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:35096003", "type": "paper", "label": "pmid:35096003"}, {"id": "source:pmid:35096003", "type": "manuscript", "label": "PMID 35096003 full text"}, {"id": "data:geo:GSE110993", "type": "dataset", "label": "GEO GSE110993"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:35096003", "type": "paper", "label": "pmid:35096003"}, {"id": "source:pmid:35096003", "type": "manuscript", "label": "PMID 35096003 full text"}, {"id": "data:geo:GSE110993", "type": "dataset", "label": "GEO GSE110993"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-35096003", "type": "extraction", "used": ["source:pmid:35096003"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE110993", "type": "accession_resolution", "used": ["data:geo:GSE110993"], "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:35096003", "parent_hash": "sha256:894ab80690b563bf024714fc18460eba9cbad9a01d99befac3bf86b7e84d31e2", "fork_of": null, "generation": 4}, "gaps": ["asset:data:geo:GSE110993 licence not read", "asset:data:geo:GSE110993 not downloaded", "asset:data:geo:GSE22255 licence not read", "asset:data:geo:GSE22255 not downloaded", "asset:data:geo:GSE58294 licence not read", "asset:data:geo:GSE58294 not downloaded", "execution.not_run", "method.reader_named_unmapped", "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": ["ies was based on the GPL570 [HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array. The GSE110", "transcriptome series was based on the GPL570 Affymetrix Human Genome U133 Plus 2.0 Array. The raw da", "Schneider et al., 2017) were downloaded from Affymetrix using the Rsubread package. In the comment p"], "order_basis": "paper_text_order:2815", "id": "assay:1"}, {"role": "analysis", "definition_id": "principal_component_analysis", "definition_version": "f2132e96ae6c7a4e", "definition_digest": null, "required_operations": ["pca_fit"], "support_state": "supported", "source_hashes": {"dsl_catalogue": "f2132e96ae6c7a4e"}, "confidence": 0.8, "evidence": ["principal component analysis"], "order_basis": "consumes_earlier_output", "id": "assay:2"}]}