Elucidating the Molecular Mechanism of Ischemic Stroke Using Integrated Analysis of miRNA, mRNA, and lncRNA Expression Profiles.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:34483854", "kind": "science-record", "revision": 8, "content_hash": "sha256:72c7afabde74145d202b209e2e3d4f3013b4b2144c575f13585a707772512529", "created_at": "2026-11-01T15:41:50Z", "updated_at": "2026-11-01T22:47:26Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Elucidating the Molecular Mechanism of Ischemic Stroke Using Integrated Analysis of miRNA, mRNA, and lncRNA Expression Profiles.", "doi": "10.3389/fnint.2021.638114", "pmid": "34483854", "authors": ["Yaxuan Sun", "Jing Wang", "Bin Han", "Kun Meng", "Yan Han", "Yongxia Ding"], "journal": "Frontiers in integrative neuroscience", "year": 2021, "abstract": "Objective: This study aimed to investigate the possible molecular mechanisms associated with ischemic stroke through the construction of a lncRNA-miRNA-mRNA network. miRNA expression profile in GSE55937, mRNA and lncRNA expression profiles in GSE122709, and mRNA expression profile in GSE146882 were downloaded from the NCBI GEO database. After the identification of the differentially expressed miRNA, lncRNA, and mRNA using GSE55937 and GSE122709 in ischemic stroke vs. control groups, a protein-protein interaction (PPI) network was constructed. The lncRNA-miRNA, lncRNA-mRNA, and miRNA-mRNA pairs were predicted, and a lncRNA-miRNA-mRNA network was constructed. Additionally, the gene-drug interactions were predicted. Characteristic genes were used to construct a support vector machine (SVM) model and verified using quantitative reverse transcription polymerase chain reaction. In total 38 miRNAs, 115 lncRNAs, and 990 mRNAs were identified between ischemic stroke and control groups. A PPI network with 371 nodes and 2306 interaction relationships was constructed. The constructed lncRNA-miRNA-mRNA network contained 7 mRNAs, 14 lncRNAs, such as SND1-IT1, NAPA-AS1, LINC01001, LUCAT1, and ASAP1-IT2, and 8 miRNAs, such as miR-93-3p and miR-24-3p. The drug action analysis of the seven differential mRNAs included in the lncRNA-miRNA-mRNA network showed that four genes (GPR17, ADORA1, OPRM1 and LPAR3) were predicted as molecular targets of drugs. The area under the curve of the constructed SVM model was 0.886. The verification results of the relative expression of RNA by qRT-PCR were consistent with the results of bioinformatics analysis. LPAR3, ADORA1, GPR17, and OPRM1 may serve as therapeutic targets of ischemic stroke. lncRNA-miRNA-mRNA regulatory axis such as SND1-IT1/NAPA-AS1/LINC01001-miR-24-3p-LPAR3/ADORA1 and LUCAT1/ASAP1-IT2-miR-93-3p-GPR17 may play important roles in the progression of ischemic stroke.", "claims": [{"id": "claim-method", "statement": "Using the linear regression and empirical Bayes method provided by R (v3.6.1) and limma (v3.42.0) (Ritchie et al., 2015)3 packages, the expression matrixes of miRNA microarray from the Affymetrix platform were subjected to differential expression analysis. The trimmed mean of M-values algorithm (Robinson and Oshlack, 2010) in R package edgeR (v3.28.0) (Robinson et al., 2010) was used to calculate the normalized factors, ordinary dispersion, and intra-gene dispersion of mRNA and lncRNA expression profiles on the Hiseq platform. Additionally, the exact test was performed to obtain the differential expression results and p value.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34483854", "locator": "sections[5] \"Identification of Differentially Expressed mRNAs, lncRNAs, and miRNAs\" paragraph 2", "quote": "Using the linear regression and empirical Bayes method provided by R (v3.6.1) and limma (v3.42.0) (Ritchie et al., 2015)3 packages, the expression matrixes of miRNA microarray from the Affymetrix platform were subjected to differential expression analysis."}, {"asset": "source:pmid:34483854", "locator": "sections[5] \"Identification of Differentially Expressed mRNAs, lncRNAs, and miRNAs\" paragraph 2", "quote": "The trimmed mean of M-values algorithm (Robinson and Oshlack, 2010) in R package edgeR (v3.28.0) (Robinson et al., 2010) was used to calculate the normalized factors, ordinary dispersion, and intra-gene dispersion of mRNA and lncRNA expression profiles on the Hiseq platform."}, {"asset": "source:pmid:34483854", "locator": "sections[5] \"Identification of Differentially Expressed mRNAs, lncRNAs, and miRNAs\" paragraph 2", "quote": "Additionally, the exact test was performed to obtain the differential expression results and p value."}], "state": "complete"}, {"id": "claim-data-access", "statement": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:34483854", "locator": "sections[23] \"Data Availability Statement\" paragraph 2", "quote": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."}], "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:34483854"], "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:GSE122709"], "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:GSE122709"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:34483854", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fnint.2021.638114", "sha256": "sha256:d7e52f3288f27dac012ffec3175eb38664f8297667980558e8969fecc8e8ccca", "bytes": 30023, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.3389/fnint.2021.638114", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8415716", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE122709", "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=GSE122709", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE122709", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM3483766", "GSM3483767", "GSM3483768", "GSM3483769", "GSM3483770", "GSM3483771", "GSM3483772", "GSM3483773", "GSM3483774", "GSM3483775", "GSM3483776", "GSM3483777", "GSM3483778", "GSM3483779", "GSM3483780"], "sample_count": 15, "group_sizes": null, "group_sizes_basis": null, "platform": "20795", "taxon": "Homo sapiens", "title": "LncRNA expression profiling of ischemic stroke patients", "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:GSE146882", "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=GSE146882", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE146882", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM4408702", "GSM4408703", "GSM4408704", "GSM4408705", "GSM4408706", "GSM4408707", "GSM4408708", "GSM4408709", "GSM4408710", "GSM4408711", "GSM4408712", "GSM4408713", "GSM4408714", "GSM4408715", "GSM4408716", "GSM4408717", "GSM4408718", "GSM4408719", "GSM4408720", "GSM4408721"], "sample_count": 20, "group_sizes": null, "group_sizes_basis": null, "platform": "23178", "taxon": "Homo sapiens", "title": "Altered lncRNAs transcriptomic profiles in atherosclerosis-induced ischemic stroke", "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:GSE55937", "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=GSE55937", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE55937", "version": null, "note": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM1348819", "GSM1348820", "GSM1348821", "GSM1348822", "GSM1348823", "GSM1348824", "GSM1348825", "GSM1348826", "GSM1348827", "GSM1348828", "GSM1348829", "GSM1348830", "GSM1348831", "GSM1348832", "GSM1348833", "GSM1348834", "GSM1348835", "GSM1348836", "GSM1348837", "GSM1348838", "GSM1348839", "GSM1348840", "GSM1348841", "GSM1348842", "GSM1348843", "GSM1348844", "GSM1348845", "GSM1348846", "GSM1348847", "GSM1348848", "GSM1348849", "GSM1348850", "GSM1348851", "GSM1348852", "GSM1348853", "GSM1348854", "GSM1348855", "GSM1348856", "GSM1348857", "GSM1348858", "GSM1348859", "GSM1348860", "GSM1348861", "GSM1348862", "GSM1348863", "GSM1348864", "GSM1348865", "GSM1348866"], "sample_count": 48, "group_sizes": null, "group_sizes_basis": null, "platform": "16384", "taxon": "Homo sapiens; synthetic construct", "title": "Cerebrovascular blood microRNA", "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:GSE122709 not downloaded", "asset:data:geo:GSE122709 licence not read", "asset:data:geo:GSE146882 not downloaded", "asset:data:geo:GSE146882 licence not read", "asset:data:geo:GSE55937 not downloaded", "asset:data:geo:GSE55937 licence not read"]}, "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": "reordered", "quote": "Using the linear regression and empirical Bayes method provided by R (v3.6.1) and limma (v3.42.0) (Ritchie et al., 2015)3 packages, the expression matrixes of miRNA microarray from the Affymetrix platform were subjected to differential expression analysis. The trimmed mean of M-values algorithm (Robinson and Oshlack, 2010) in R package edgeR (v3.28.0) (Robinson et al., 2010) was used to calculate the normalized factors, ordinary dispersion, and intra-gene dispersion of mRNA and lncRNA expression profiles on the Hiseq platform. Additionally, the exact test was performed to obtain the differential expression results and p value."}}, {"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": "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": "support vector machine"}}, {"id": "method-4", "family": "regression_modelling", "specific": "ols", "label": "Regression modelling", "dsl_operations": ["ols_fit"], "missing_operations": [], "expressible": true, "parameters": {}, "data_shapes": ["predictors_and_outcome"], "evidence": {"score": 0.8, "band": "high", "quote": "linear regression"}}, {"id": "method-5", "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-6", "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": "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: 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": "R1", "reachable": true, "accessions": ["GSE55937", "GSE122709", "GSE146882"], "resolved_accessions": ["GSE55937", "GSE122709", "GSE146882"], "statements": ["The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author/s."], "basis": "The paper names GSE55937, GSE122709, GSE146882 in NCBI GEO database 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:34483854", "data:geo:GSE122709"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE122709"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:34:22Z", "independence": "single_reader"}, "evidence_check": {"method": "reordered", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 23932, "completion_tokens": 2173, "cached_tokens": 8200}}, "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:34483854", "type": "paper", "label": "pmid:34483854"}, {"id": "source:pmid:34483854", "type": "manuscript", "label": "PMID 34483854 full text"}, {"id": "data:geo:GSE122709", "type": "dataset", "label": "GEO GSE122709"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:34483854", "type": "paper", "label": "pmid:34483854"}, {"id": "source:pmid:34483854", "type": "manuscript", "label": "PMID 34483854 full text"}, {"id": "data:geo:GSE122709", "type": "dataset", "label": "GEO GSE122709"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-34483854", "type": "extraction", "used": ["source:pmid:34483854"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE122709", "type": "accession_resolution", "used": ["data:geo:GSE122709"], "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:34483854", "parent_hash": "sha256:96a9abd5b5cb3ebd9927b49886d52874b46db6a60875a25e5a1ccef5abc01782", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE122709 licence not read", "asset:data:geo:GSE122709 not downloaded", "asset:data:geo:GSE146882 licence not read", "asset:data:geo:GSE146882 not downloaded", "asset:data:geo:GSE55937 licence not read", "asset:data:geo:GSE55937 not downloaded", "execution.not_run", "review.human_critique", "review.independent_reader", "review.machine_critique"], "assays": [{"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": ["Using the linear regression and empirical Bayes method provided by R (v3.6.1) and limma (v3.42.0) (Ritchie et al., 2015)3 packages, the expression matrixes of miRNA microarray from the Affymetrix platform were subjected to differential expression analysis. The trimmed mean of M-values algorithm (Robinson and Oshlack, 2010) in R package edgeR (v3.28.0) (Robinson et al., 2010) was used to calculate the normalized factors, ordinary dispersion, and intra-gene dispersion of mRNA and lncRNA expression profiles on the Hiseq platform. Additionally, the exact test was performed to obtain the differential expression results and p value."], "order_basis": "analysis_only", "id": "assay:1"}]}