Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage.

{"sci_version": "1.2", "schema": "https://corpus.bntrg.co.uk/sci/1.0/sci.schema.json", "id": "pmid:33990177", "kind": "science-record", "revision": 8, "content_hash": "sha256:6bcf1579ed6a66f7f463824e6ea37e51589d66f251dbd0dfbdbdeb6ee90479ca", "created_at": "2026-11-01T15:41:35Z", "updated_at": "2026-11-01T22:46:41Z", "generator": {"name": "corpus-assay-engine", "run_id": "reading-sci-2026-11-01"}, "paper": {"state": "complete", "title": "Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage.", "doi": "10.1186/s12883-021-02156-1", "pmid": "33990177", "authors": ["Wei Leng", "Dan Fan", "Zhong Ren", "Qiaoying Li"], "journal": "BMC neurology", "year": 2021, "abstract": "BACKGROUND: This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA).\nMETHODS: Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337.\nRESULTS: Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337.\nCONCLUSION: LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.", "claims": [{"id": "claim-method", "statement": "Then, the significantly DERs (, including lncRNA and mRNA) between SAH group and normal controls were identified using Limma package (version 3.34.0, https://bioconductor.org/packages/release/bioc/html/limma.html) in R3.4.1, with the threshold of false discovery rate (FDR) < 0.05 and |logFC| > 0.5.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33990177", "locator": "sections[4] \"Identification of differentially expressed RNAs (DERs) and functional analyses\" paragraph 2", "quote": "Then, the significantly DERs (, including lncRNA and mRNA) between SAH group and normal controls were identified using Limma package (version 3.34.0, https://bioconductor.org/packages/release/bioc/html/limma.html) in R3.4.1, with the threshold of false discovery rate (FDR) < 0.05 and |logFC| > 0.5."}], "state": "complete"}, {"id": "claim-data-access", "statement": "Availability of data and materialsThe datasets analysed during the current study are available in the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database (https://www.ncbi.nlm.nih.gov/geo/). We downloaded two datasets: GSE36791 and GSE7337.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:33990177", "locator": "sections[24] \"notes\" paragraph 1", "quote": "Availability of data and materialsThe datasets analysed during the current study are available in the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database (https://www.ncbi.nlm.nih.gov/geo/). We downloaded two datasets: GSE36791 and GSE7337."}], "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:33990177"], "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:GSE36791"], "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:GSE36791"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:33990177", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.1186/s12883-021-02156-1", "sha256": "sha256:a4298422f9a047ca9633d336456856561b366193985ba65a1a1b79acf5255b29", "bytes": 25698, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "10.1186/s12883-021-02156-1", "version": null, "note": "Full article fetched from PMC; the checksum covers the rendered section body, not the original XML bytes.", "structure": {"pmcid": "PMC8120017", "source": "europe_pmc_fulltext", "coverage": "whole_body_without_references", "text_hash_scope": "rendered_section_body"}}, {"id": "data:geo:GSE36791", "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=GSE36791", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE36791", "version": null, "note": "Availability of data and materialsThe datasets analysed during the current study are available in the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database (https://www.ncbi.nlm.nih.gov/geo/). We downloaded two datasets: GSE36791 and GSE7337.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Availability of data and materialsThe datasets analysed during the current study are available in the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database (https://www.ncbi.nlm.nih.gov/geo/). We downloaded two datasets: GSE36791 and GSE7337.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM901102", "GSM901103", "GSM901104", "GSM901105", "GSM901106", "GSM901107", "GSM901108", "GSM901109", "GSM901110", "GSM901111", "GSM901112", "GSM901113", "GSM901114", "GSM901115", "GSM901116", "GSM901117", "GSM901118", "GSM901119", "GSM901120", "GSM901121", "GSM901122", "GSM901123", "GSM901124", "GSM901125", "GSM901126", "GSM901127", "GSM901128", "GSM901129", "GSM901130", "GSM901131", "GSM901132", "GSM901133", "GSM901134", "GSM901135", "GSM901136", "GSM901137", "GSM901138", "GSM901139", "GSM901140", "GSM901141", "GSM901142", "GSM901143", "GSM901144", "GSM901145", "GSM901146", "GSM901147", "GSM901148", "GSM901149", "GSM901150", "GSM901151", "GSM901152", "GSM901153", "GSM901154", "GSM901155", "GSM901156", "GSM901157", "GSM901158", "GSM901159", "GSM901160", "GSM901161", "GSM901162"], "sample_count": 61, "group_sizes": null, "group_sizes_basis": null, "platform": "10558", "taxon": "Homo sapiens", "title": "Gene expression profiling of blood in ruptured intracranial aneurysms", "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:GSE7337", "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=GSE7337", "sha256": null, "bytes": null, "access": "open", "state": "resolved", "reader": null, "reader_status": "reader_required", "identifier": "GSE7337", "version": null, "note": "Availability of data and materialsThe datasets analysed during the current study are available in the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database (https://www.ncbi.nlm.nih.gov/geo/). We downloaded two datasets: GSE36791 and GSE7337.", "structure": {"repository": "GEO", "access_route": "GEO accession URL", "access_statement_verbatim": "Availability of data and materialsThe datasets analysed during the current study are available in the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database (https://www.ncbi.nlm.nih.gov/geo/). We downloaded two datasets: GSE36791 and GSE7337.", "access_statement_kind": "data_availability_statement", "sample_accessions": ["GSM176869", "GSM176894", "GSM176895", "GSM176896", "GSM176898", "GSM176900"], "sample_count": 6, "group_sizes": null, "group_sizes_basis": null, "platform": "90", "taxon": "Saccharomyces cerevisiae", "title": "Histone H2A^4-20", "resolution_checked_at": "2026-11-01T15:39:55Z", "resolution_check": "identifier_resolution_only_no_download_no_licence_read", "downloaded": false, "licence_read": false}}, {"id": "asset:table:pmid:33990177:1", "role": "table", "format": "jats-table", "media_type": "application/vnd.jats.table+json", "uri": null, "sha256": "sha256:86b6886e33c392a41ea8fd1f0811dc1b74c5edb989be7959c438b2c7e9c8639d", "bytes": 1068, "access": "open", "state": "verified", "reader": "read_table", "reader_status": "available", "identifier": "section[13]/table-wrap[1]#Tab1", "version": null, "note": "KEGG pathways associated with LINC00265 and LINC00937 and the target genes", "structure": {"pmcid": "PMC8120017", "section_index": 13, "section_title": "GSEA for the lncRNAs in regulatory network", "row_count": 12, "column_count": 6}, "table": {"label": "Table 1", "caption": "KEGG pathways associated with LINC00265 and LINC00937 and the target genes", "rows": [["Name", "SIZE", "ES", "NES", "NOM p-val", "Gene"], ["LINC00265"], ["Cytokine-cytokine receptor interaction", "3", "0.7413", "1.5656", "0.0042", "IL4R"], ["Neurotrophin signaling pathway", "2", "0.6761", "1.2246", "0.0226", "IRAK3,MAPK14"], ["Apoptosis", "2", "0.6731", "1.2001", "0.0269", "IRAK3, CFLAR"], ["Neuroactive ligand receptor interaction", "2", "0.5909", "1.1584", "0.0309", "C3AR1, FPR2"], ["LINC00937"], ["Apoptosis", "3", "−0.7738", "−1.6314", "0.0036", "IRAK3, CFLAR, NFKBIA"], ["Toll like receptor signaling pathway", "6", "−0.4242", "−1.2428", "0.0178", "NFKBIA,MAPK14,TLR8,TLR5,TLR4,TLR2"], ["Neurotrophin signaling pathway", "3", "−0.5119", "−1.0841", "0.0353", "IRAK3,NFKBIA,MAPK14"], ["Cytokine-cytokine receptor interaction", "4", "0.6016", "1.4480", "0.0080", "IL1R2,IL18RAP,IL18R1"], ["MAPK signaling pathway", "3", "0.5000", "0.9982", "0.0489", "IL1R2,MKNK1,MAPK14"]], "row_count": 12, "column_count": 6, "numeric_cells": 43, "header_rows": 1, "locator": "section[13]/table-wrap[1]#Tab1"}}], "gaps": ["asset:data:geo:GSE36791 not downloaded", "asset:data:geo:GSE36791 licence not read", "asset:data:geo:GSE7337 not downloaded", "asset:data:geo:GSE7337 licence not read"]}, "analysis": {"state": "complete", "methods": [{"id": "method-1", "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": 1.0, "band": "verbatim", "quote": "Then, the significantly DERs (, including lncRNA and mRNA) between SAH group and normal controls were identified using Limma package (version 3.34.0, https://bioconductor.org/packages/release/bioc/html/limma.html) in R3.4.1, with the threshold of false discovery rate (FDR) < 0.05 and |logFC| > 0.5."}}, {"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"}}], "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: limma_voom."}, "capability": {"tier": "R1", "capability_id": "capability:computational_analysis", "availability_state": "owned", "basis": "The computational analysis is owned. 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No dataset was downloaded and no licence was read."}}, "can_run": {"dsl_operations": ["normalise_counts", "differential_expression_fit", "fdr_bh"], "assets": ["source:pmid:33990177", "data:geo:GSE36791", "asset:table:pmid:33990177:1"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE36791"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-10-31T18:30:05Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 3, "usage": {"prompt_tokens": 20464, "completion_tokens": 1992, "cached_tokens": 792}}, "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:33990177", "type": "paper", "label": "pmid:33990177"}, {"id": "source:pmid:33990177", "type": "manuscript", "label": "PMID 33990177 full text"}, {"id": "data:geo:GSE36791", "type": "dataset", "label": "GEO GSE36791"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:33990177", "type": "paper", "label": "pmid:33990177"}, {"id": "source:pmid:33990177", "type": "manuscript", "label": "PMID 33990177 full text"}, {"id": "data:geo:GSE36791", "type": "dataset", "label": "GEO GSE36791"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-33990177", "type": "extraction", "used": ["source:pmid:33990177"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE36791", "type": "accession_resolution", "used": ["data:geo:GSE36791"], "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:33990177", "parent_hash": "sha256:362e38f663103ed5fbb378285bcf44d8ecc521fc46ec1c896804cf7a15bb3137", "fork_of": null, "generation": 7}, "gaps": ["asset:data:geo:GSE36791 licence not read", "asset:data:geo:GSE36791 not downloaded", "asset:data:geo:GSE7337 licence not read", "asset:data:geo:GSE7337 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": 0.93, "evidence": ["ptured intracranial aneurysm (RIA). METHODS: Microarray GSE36791 was downloaded from Gene Expression"], "order_basis": "paper_text_order:288", "id": "assay:1"}, {"role": "data_generation", "definition_id": "apoptosis_assay", "definition_version": "99e1195c7d6f", "definition_digest": null, "required_operations": [], "support_state": "partial", "source_hashes": {"assay_lexicon": "99e1195c7d6f"}, "confidence": 0.93, "evidence": ["raction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in", "ed in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associat"], "order_basis": "paper_text_order:1509", "id": "assay:2"}, {"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": ["Then, the significantly DERs (, including lncRNA and mRNA) between SAH group and normal controls were identified using Limma package (version 3.34.0, https://bioconductor.org/packages/release/bioc/html/limma.html) in R3.4.1, with the threshold of false discovery rate (FDR) < 0.05 and |logFC| > 0.5."], "order_basis": "consumes_earlier_output", "id": "assay:3"}]}