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基于生存分析和多组学肿瘤数据整合的癌症亚型有监督图聚类。

Supervised Graph Clustering for Cancer Subtyping Based on Survival Analysis and Integration of Multi-Omic Tumor Data.

出版信息

IEEE/ACM Trans Comput Biol Bioinform. 2022 Mar-Apr;19(2):1193-1202. doi: 10.1109/TCBB.2020.3010509. Epub 2022 Apr 1.

Abstract

Identifying cancer subtypes by integration of multi-omic data is beneficial to improve the understanding of disease progression, and provides more precise treatment for patients. Cancer subtypes identification is usually accomplished by clustering patients with unsupervised learning approaches. Thus, most existing integrative cancer subtyping methods are performed in an entirely unsupervised way. An integrative cancer subtyping approach can be improved to discover clinically more relevant cancer subtypes when considering the clinical survival response variables. In this study, we propose a Survival Supervised Graph Clustering (S2GC)for cancer subtyping by taking into consideration survival information. Specifically, we use a graph to represent similarity of patients, and develop a multi-omic survival analysis embedding with patient-to-patient similarity graph learning for cancer subtype identification. The multi-view (omic)survival analysis model and graph of patients are jointly learned in a unified way. The learned optimal graph can be unitized to cluster cancer subtypes directly. In the proposed model, the survival analysis model and adaptive graph learning could positively reinforce each other. Consequently, the survival time can be considered as supervised information to improve the quality of the similarity graph and explore clinically more relevant subgroups of patients. Experiments on several representative multi-omic cancer datasets demonstrate that the proposed method achieves better results than a number of state-of-the-art methods. The results also suggest that our method is able to identify biologically meaningful subgroups for different cancer types. (Our Matlab source code is available online at github: https://github.com/CLiu272/S2GC).

摘要

通过整合多组学数据来识别癌症亚型有助于提高对疾病进展的理解,并为患者提供更精确的治疗。癌症亚型的识别通常通过无监督学习方法对患者进行聚类来完成。因此,大多数现有的整合癌症亚型方法都是完全无监督的。当考虑临床生存反应变量时,整合癌症亚型方法可以通过考虑生存信息来改进,以发现更具临床相关性的癌症亚型。在这项研究中,我们提出了一种基于生存信息的生存监督图聚类(S2GC)方法,用于癌症亚型识别。具体来说,我们使用图来表示患者之间的相似性,并开发了一种具有患者到患者相似性图学习的多组学生存分析嵌入方法,用于癌症亚型识别。多视图(组学)生存分析模型和患者图以统一的方式进行联合学习。学习到的最优图可以直接用于聚类癌症亚型。在提出的模型中,生存分析模型和自适应图学习可以相互促进。因此,生存时间可以被视为监督信息,以提高相似性图的质量,并探索更具临床相关性的患者亚组。在几个具有代表性的多组学癌症数据集上的实验表明,该方法优于许多最新方法。结果还表明,我们的方法能够为不同类型的癌症识别出具有生物学意义的亚组。(我们的 Matlab 源代码可在 github 上获得:https://github.com/CLiu272/S2GC)。

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