Department of Pathology, Stanford University, Stanford, CA, 94305, USA.
Department of Computer Science, Stanford University, Stanford, CA, 94305, USA.
Nat Commun. 2018 Oct 26;9(1):4453. doi: 10.1038/s41467-018-06921-8.
Outcomes for cancer patients vary greatly even within the same tumor type, and characterization of molecular subtypes of cancer holds important promise for improving prognosis and personalized treatment. This promise has motivated recent efforts to produce large amounts of multidimensional genomic (multi-omic) data, but current algorithms still face challenges in the integrated analysis of such data. Here we present Cancer Integration via Multikernel Learning (CIMLR), a new cancer subtyping method that integrates multi-omic data to reveal molecular subtypes of cancer. We apply CIMLR to multi-omic data from 36 cancer types and show significant improvements in both computational efficiency and ability to extract biologically meaningful cancer subtypes. The discovered subtypes exhibit significant differences in patient survival for 27 of 36 cancer types. Our analysis reveals integrated patterns of gene expression, methylation, point mutations, and copy number changes in multiple cancers and highlights patterns specifically associated with poor patient outcomes.
即使在同一肿瘤类型中,癌症患者的预后也有很大差异,因此对癌症分子亚型进行特征描述对于改善预后和实现个体化治疗具有重要意义。这种前景促使人们最近努力产生大量多维基因组(多组学)数据,但目前的算法在对这些数据进行综合分析时仍然面临挑战。在这里,我们提出了通过多核学习进行癌症整合(Cancer Integration via Multikernel Learning,CIMLR),这是一种新的癌症亚型分类方法,可整合多组学数据以揭示癌症的分子亚型。我们将 CIMLR 应用于 36 种癌症的多组学数据,结果表明在计算效率和提取生物学意义上的癌症亚型的能力方面都有显著提高。对于 36 种癌症中的 27 种,所发现的亚型在患者生存方面存在显著差异。我们的分析揭示了多种癌症中基因表达、甲基化、点突变和拷贝数变化的综合模式,并突出了与患者预后不良特别相关的模式。
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