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pmid:39660117
Multi-modal transcriptomics: integrating machine learning and convolutional neural networks to identify immune biomarkers in atherosclerosis.
Haiqing Chen · Haotian Lai · Hao Chi · Wei Fan · Jinbang Huang · Shengke Zhang · Chenglu Jiang · Lai Jiang · Qingwen Hu · Xiuben Yan · Yemeng Chen · Jieying Zhang · Guanhu Yang · Bin Liao · Juyi Wan
Frontiers in cardiovascular medicine · 2024 doi:10.3389/fcvm.2024.1397407
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Experiment
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Analysis
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Execution
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Complete file
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Nevertheless, our current understanding of its pathogenesis remains imprecise. In this investigation, our objective is to establish computational models elucidating molecular-level markers associated with atherosclerosis. This endeavor involves the integration of advanced machine learning techniques and comprehensive bioinformatics analyses.\nMaterials and methods: Our analysis incorporated data from three publicly available the Gene Expression Omnibus (GEO) datasets: GSE100927 (104 samples, 30,558 genes), which includes atherosclerotic lesions and control arteries from carotid, femoral, and infra-popliteal arteries of deceased organ donors; GSE43292 (64 samples, 23,307 genes), consisting of paired carotid endarterectomy samples from 32 hypertensive patients, comparing atheroma plaques and intact tissues; and GSE159677 (30,498 single cells, 33,538 genes), examining single-cell transcriptomes of calcified atherosclerotic core plaques and adjacent carotid artery tissues from patients undergoing carotid endarterectomy. Utilizing single-cell sequencing, highly variable atherosclerotic monocyte subpopulations were systematically identified. We analyzed cellular communication patterns with temporal dynamics. The bioinformatics approach Weighted Gene Co-expression Network Analysis (WGCNA) identified key modules, constructing a Protein-Protein Interaction (PPI) network from module-associated genes. Three machine-learning models derived marker genes, formulated through logistic regression and validated via convolutional neural network(CNN) modeling. Subtypes were clustered based on Gene Set Variation Analysis (GSVA) scores, validated through immunoassays.\nResults: Three pivotal atherosclerosis-associated genes-CD36, S100A10, CSNK1A1-were unveiled, offering valuable clinical insights. Profiling based on these genes delineated two distinct isoforms: C2 demonstrated potent microbicidal activity, while C1 engaged in inflammation regulation, tissue repair, and immune homeostasis. Molecular docking analyses explored therapeutic potential for Estradiol, Zidovudine, Indinavir, and Dronabinol for clinical applications.\nConclusion: This study introduces three signature genes for atherosclerosis, shaping a novel paradigm for investigating clinical immunological medications. It distinguishes the high biocidal C2 subtype from the inflammation-modulating C1 subtype, utilizing identified signature gene as crucial targets.", "claims": [{"id": "claim-method", "statement": "One-way analysis of variance (ANOVA) and t-tests were employed to explore potential significant differences in atherosclerosis model genes, functional enrichment results, immune cell infiltration, and immune function scores among the patient groups.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39660117", "locator": "sections[14] \"Statistical analysis\" paragraph 2", "quote": "One-way analysis of variance (ANOVA) and t-tests were employed to explore potential significant differences in atherosclerosis model genes, functional enrichment results, immune cell infiltration, and immune function scores among the patient groups."}], "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 authors.", "kind": "methodological", "target": null, "evidence": [{"asset": "source:pmid:39660117", "locator": "sections[31] \"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 authors."}], "state": "complete"}, {"id": "claim-target-result", "statement": "Three pivotal atherosclerosis-associated genes—CD36, S100A10, CSNK1A1—were unveiled, offering valuable clinical insights.", "kind": "qualitative", "target": null, "evidence": [{"asset": "source:pmid:39660117", "locator": "sections[0] \"Abstract\" paragraph 3", "quote": "Three pivotal atherosclerosis-associated genes—CD36, S100A10, CSNK1A1—were unveiled, offering valuable clinical insights."}], "state": "complete"}], "gaps": []}, "experiment": {"state": "complete", "objective": "Three pivotal atherosclerosis-associated genes—CD36, S100A10, CSNK1A1—were unveiled, offering valuable clinical insights.", "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:39660117"], "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. 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