CLCluster:一种基于多组学数据的基于冗余减少对比学习的癌症亚型聚类方法。

IF 6.1 2区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL
Molecular Therapy. Nucleic Acids Pub Date : 2025-04-02 eCollection Date: 2025-06-10 DOI:10.1016/j.omtn.2025.102534
Hong Wang, Yi Zhang, Wen Li, Zhen Wei, Zhenlong Wang, Mengyuan Yang
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引用次数: 0

摘要

选择性剪接(AS)允许一个基因产生几个蛋白质变体,为癌症预测和促进靶向治疗提供了有价值的见解。虽然多组学数据用于识别癌症亚型,但AS很少用于此目的。在这里,我们提出了一种基于拷贝数变化、甲基化、基因表达、miRNA表达和AS的冗余减少对比学习方法(CLCluster),用于33种癌症类型的癌症亚型聚类。消融实验强调了使用AS数据对癌症亚型的益处。我们确定了与患者生存相关的2,921种癌症亚型相关的AS事件,并进行了多项分析,包括开放阅读框注释、RNA结合蛋白(RBP)相关的AS调节和治疗性生物标志物的剪接相关抗癌肽(ACPs)预测。与其他模型相比,CLCluster模型在识别与预后相关的癌症亚型方面更有效。癌症亚型相关AS事件的有效注释有助于识别患者的治疗靶向生物标志物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
CLCluster: A redundancy-reduction contrastive learning-based clustering method of cancer subtype based on multi-omics data.

Alternative splicing (AS) allows one gene to produce several protein variants, offering valuable predictive insights into cancer and facilitating targeted therapies. Although multi-omics data are used to identify cancer subtypes, AS is rarely utilized for this purpose. Here, we propose a redundancy-reduction contrastive learning-based method (CLCluster) based on copy number variation, methylation, gene expression, miRNA expression, and AS for cancer subtype clustering of 33 cancer types. Ablation experiments emphasize the benefits of using AS data to subtype cancer. We identified 2,921 cancer subtype-related AS events associated with patient survival and conducted multiple analyses including open reading frame annotation, RNA binding protein (RBP)-associated AS regulation, and splicing-related anticancer peptides (ACPs) prediction for therapeutic biomarkers. The CLCluster model is more effective in identifying prognostic-relevant cancer subtypes than other models. The effective annotation of cancer subtype related AS events facilitates the identification of therapeutically targetable biomarkers in patients.

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来源期刊
Molecular Therapy. Nucleic Acids
Molecular Therapy. Nucleic Acids MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
15.40
自引率
1.10%
发文量
336
审稿时长
20 weeks
期刊介绍: Molecular Therapy Nucleic Acids is an international, open-access journal that publishes high-quality research in nucleic-acid-based therapeutics to treat and correct genetic and acquired diseases. It is the official journal of the American Society of Gene & Cell Therapy and is built upon the success of Molecular Therapy. The journal focuses on gene- and oligonucleotide-based therapies and publishes peer-reviewed research, reviews, and commentaries. Its impact factor for 2022 is 8.8. The subject areas covered include the development of therapeutics based on nucleic acids and their derivatives, vector development for RNA-based therapeutics delivery, utilization of gene-modifying agents like Zn finger nucleases and triplex-forming oligonucleotides, pre-clinical target validation, safety and efficacy studies, and clinical trials.
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