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pmid:37057098
Comprehensive analysis of atherosclerotic plaques reveals crucial genes and molecular mechanisms associated with plaque progression and rupture.
Guoqi Zhu · Yanhua Gao · Jun Qian · Yan Lai · Hao Lin · Chengxing Liu · Fei Chen · Xuebo Liu
Frontiers in cardiovascular medicine · 2023 doi:10.3389/fcvm.2023.951242
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Experiment
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Complete file
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This article aimed to explore the gene signatures and potential molecular mechanisms in the progression and instability of APs and to identify novel biomarkers and interventional targets for AP rupture.\nMethods: The microarray data were downloaded from the Gene Expression Omnibus (GEO) database and grouped into discovery and validation cohorts. In the discovery cohort, Weighted Gene Co-Expression Network Analysis was performed for finding co-expression modules, and the Metascape database was used to perform functional enrichment analysis. Differential Expression Genes analysis subsequently was performed in the validation cohort for verification of the obtained results. Common genes were introduced into Metascape database for protein-protein interaction and functional enrichment analysis. We constructed the miRNAs-mRNAs network with the hub genes. Moreover, gene expression profiles of peripheral blood mononuclear cells (PBMCs) from peripheral blood of patients with plaque rupture were analyzed by high-throughput sequencing, and the diagnostic power of hub genes was verified by receiver operating characteristic (ROC) analysis.\nResults: In the discovery cohort, the brown module in GSE28829 and the turquoise module in GSE163154 were the most significant co-expression modules. Functional enrichment analysis of shared genes suggested that \"Neutrophil degranulation\" was the most significantly enriched pathway. These conclusions were also demonstrated by the validation cohort. A total of 16 hub genes were identified. The miRNA-mRNA network revealed that hsa-miR-665 and hsa-miR-512-3p might regulate the \"Neutrophil degranulation\" pathway through PLAU and SIRPA, which might play a significant role in AP progression and instability. Five hub genes, including PLAUR, FCER1G, PLAU, ITGB2, and SLC2A5, showed significantly increased expression in PBMCs from patients with plaque rupture compared with controls. ROC analysis finally identified three hub genes PLAUR, FCER1G, and PLAU that could effectively distinguish patients with APs rupture from controls.\nConclusions: The present study demonstrated that the \"neutrophil degranulation\" signaling pathways and identified novel mRNA and miRNA candidates are closely associated with plaque progression and instability. 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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:37057098", "data:geo:GSE163154"], "steps": ["run_analysis"]}, "must_build": {"dsl_operations": [], "converters": [], "readers": [], "capabilities": [], "data_gaps": ["data:geo:GSE163154"]}, "gaps": []}, "review": {"state": "partial", "machine_critique": {"kind": "extraction_review", "reader": {"model": "MiniMax-M3.1-Flash", "provider": "minimax", "provider_family": "minimax", "read_at": "2026-11-01T18:36:26Z", "independence": "single_reader"}, "evidence_check": {"method": "verbatim", "availability": "verbatim"}, "calls": 5, "usage": {"prompt_tokens": 11131, "completion_tokens": 1695, "cached_tokens": 256}}, "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:37057098", "type": "paper", "label": "pmid:37057098"}, {"id": "source:pmid:37057098", "type": "manuscript", "label": "PMID 37057098 full text"}, {"id": "data:geo:GSE163154", "type": "dataset", "label": "GEO GSE163154"}], "activities": [{"id": "activity-reading-sci-2026-11-01", "type": "classification", "used": [{"id": "pmid:37057098", "type": "paper", "label": "pmid:37057098"}, {"id": "source:pmid:37057098", "type": "manuscript", "label": "PMID 37057098 full text"}, {"id": "data:geo:GSE163154", "type": "dataset", "label": "GEO GSE163154"}], "agent": "agent:corpus-assay-engine"}, {"id": "activity-read-37057098", "type": "extraction", "used": ["source:pmid:37057098"], "agent": "agent:minimax-reader"}, {"id": "activity-resolve-GSE163154", "type": "accession_resolution", "used": ["data:geo:GSE163154"], "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:37057098", "parent_hash": "sha256:d70db0a9ddeeb1dcb0d518607a77b5b7a29adb0c73ae7eaf0915e8d60db38bc6", "fork_of": null, "generation": 2}, "gaps": ["asset:data:geo:GSE163154 licence not read", "asset:data:geo:GSE163154 not downloaded", "asset:data:geo:GSE28829 licence not read", "asset:data:geo:GSE28829 not downloaded", "asset:data:geo:GSE41571 licence not read", "asset:data:geo:GSE41571 not downloaded", "asset:data:geo:GSE66360 licence not read", "asset:data:geo:GSE66360 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": 0.93, "evidence": ["ntional targets for AP rupture. Methods: The microarray data were downloaded from the Gene Expressio"], "order_basis": "paper_text_order:531", "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"}]}