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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

Paper

complete

Experiment

complete

Data

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Analysis

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Execution

absent

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Record details sci_version · id · kind · revision · content_hash · schema · created_at · updated_at · generator
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2026-11-01T20:29:57Z
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title
Multi-modal transcriptomics: integrating machine learning and convolutional neural networks to identify immune biomarkers in atherosclerosis.
doi
10.3389/fcvm.2024.1397407
pmid
39660117
authors array · 15 items
[0]
Haiqing Chen
[1]
Haotian Lai
[2]
Hao Chi
[3]
Wei Fan
[4]
Jinbang Huang
[5]
Shengke Zhang
[6]
Chenglu Jiang
[7]
Lai Jiang
[8]
Qingwen Hu
[9]
Xiuben Yan
[10]
Yemeng Chen
[11]
Jieying Zhang
[12]
Guanhu Yang
[13]
Bin Liao
[14]
Juyi Wan
journal
Frontiers in cardiovascular medicine
year
2024
abstract
Background: Atherosclerosis, a complex chronic vascular disorder with multifactorial etiology, stands as the primary culprit behind consequential cardiovascular events, imposing a substantial societal and economic burden. 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. Materials 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. Results: 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. Conclusion: 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.
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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.
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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.
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Three pivotal atherosclerosis-associated genes—CD36, S100A10, CSNK1A1—were unveiled, offering valuable clinical insights.
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[2]
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evidence array · 4 items
[0]
Multi-modal transcriptomics: integrating machine learning and convolutio
[1]
g. Supplementary Figure S2Quality control of transcriptome data. (A) boxplot of intergroup batch effect
[2]
cells, 33,538 genes), examining single-cell transcriptomes of calcified atherosclerotic core plaques an
[3]
dataset. This dataset comprises single-cell RNA-seq data derived from three atherosclerotic core
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he GSE159677 dataset. This dataset comprises single-cell RNA-seq data derived from three atherosclerotic core
[1]
al Supplementary Figure S1Quality control of scRNA-seq data (A) Expression of scRNA-seq data before
[2]
control of scRNA-seq data (A) Expression of scRNA-seq data before quality control. (A) Each point
[3]
e total UMIs in each cell; (B) Expression of scRNA-seq data after quality control; (C) UMIs vs. sca
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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.
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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. This lane did not download the dataset or read its licence.", "duration_hours": null, "parameters": {}, "inputs": ["data:geo:GSE100927"], "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:GSE100927"], "outputs": ["the replicated result and its comparison"], "instruments": [], "reagents": []}], "materials": [], "instruments": [], "reagents": [], "conditions": {}, "gaps": []}, "data": {"state": "partial", "assets": [{"id": "source:pmid:39660117", "role": "manuscript", "format": "xml", "media_type": "application/xml", "uri": "https://doi.org/10.3389/fcvm.2024.1397407", "sha256": 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