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基于全对和弱对多组学数据的多视图对比聚类进行癌症亚型分析。

Multi-view contrastive clustering for cancer subtyping using fully and weakly paired multi-omics data.

机构信息

College of Information Science and Engineering, Hunan Normal University, China.

School of Software Engineering, Beijing Jiaotong University, China.

出版信息

Methods. 2024 Dec;232:1-8. doi: 10.1016/j.ymeth.2024.09.016. Epub 2024 Oct 17.

Abstract

The identification of cancer subtypes is crucial for advancing precision medicine, as it facilitates the development of more effective and personalized treatment and prevention strategies. With the development of high-throughput sequencing technologies, researchers now have access to a wealth of multi-omics data from cancer patients, making computational cancer subtyping increasingly feasible. One of the main challenges in integrating multi-omics data is handling missing data, since not all biomolecules are consistently measured across all samples. Current computational models based on multi-omics data for cancer subtyping often struggle with the challenge of weakly paired omics data. To address this challenge, we propose a novel unsupervised cancer subtyping model named Subtype-MVCC. This model leverages graph convolutional networks to extract and represent low-dimensional features from each omics data type, using intra-view and inter-view contrastive learning approaches. By incorporating a weighted average fusion strategy to unify the dimension of each sample, Subtype-MVCC effectively handles weakly paired multi-omics datasets. Comprehensive evaluations on established benchmark datasets demonstrate that Subtype-MVCC outperforms nine leading models in this domain. Additionally, simulations with varying levels of missing data highlight the model's robust performance in handling weakly paired omics data. The clinical relevance and survival outcomes associated with the identified subtypes further validate the interpretability and reliability of the clustering results produced by Subtype-MVCC.

摘要

癌症亚型的鉴定对于推进精准医学至关重要,因为它有助于制定更有效和个性化的治疗和预防策略。随着高通量测序技术的发展,研究人员现在可以从癌症患者那里获得大量的多组学数据,这使得计算癌症亚型分类越来越可行。整合多组学数据的主要挑战之一是处理缺失数据,因为并非所有生物分子在所有样本中都能被一致测量到。目前基于多组学数据的癌症亚型分类的计算模型通常难以应对弱配对组学数据的挑战。为了解决这个挑战,我们提出了一种名为 Subtype-MVCC 的新型无监督癌症亚型分类模型。该模型利用图卷积网络从每个组学数据类型中提取和表示低维特征,使用内视图和视图间对比学习方法。通过采用加权平均融合策略来统一每个样本的维度,Subtype-MVCC 有效地处理了弱配对多组学数据集。在已建立的基准数据集上的综合评估表明,Subtype-MVCC 在该领域优于九种领先模型。此外,在不同缺失数据水平下的模拟突出了该模型在处理弱配对组学数据方面的稳健性能。与鉴定出的亚型相关的临床相关性和生存结果进一步验证了 Subtype-MVCC 产生的聚类结果的可解释性和可靠性。

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