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利用多任务分类框架预测核心癌症基因。

Prediction of core cancer genes using multi-task classification framework.

机构信息

Applied Bioinformatics Laboratory, The University of Kansas, 2034 Becker Drive, Lawrence, KS 66047, USA.

出版信息

J Theor Biol. 2013 Jan 21;317:62-70. doi: 10.1016/j.jtbi.2012.09.027. Epub 2012 Oct 3.

Abstract

Cancer is deemed as a highly heterogeneous disease specific to cell type and tissue origin. All cancers, however, share a common pathogenesis. Therefore, it is widely believed that cancers may share common mechanisms. In this study, we introduce a novel strategy based on multi-tasking learning methods to predict core cancer genes shared by multiple cancers in the hope of elucidating common cancer mechanisms. Our strategy uses two multi-tasking learning algorithms, one for feature selection and the other for validation of selected features. The combined use of two methods results in more robust classifiers and reliable selected features. The top 73 significant features, mapped to 72 genes, are selected as core cancer genes. The effectiveness of the 73 features is further demonstrated in a blind test conducted on an independent test data. The biological significance of these genes is evaluated using systems biology analyses. Extensive functional, pathway and network analysis confirms findings in previous studies and brings new insights into common cancer mechanisms. Our strategy can be used as a general method to find important genes from large gene expression datasets on the genomic level. The selected genes can be used to predict cancers.

摘要

癌症被认为是一种高度异质性的疾病,特定于细胞类型和组织起源。然而,所有癌症都有共同的发病机制。因此,人们普遍认为癌症可能有共同的机制。在这项研究中,我们引入了一种基于多任务学习方法的新策略,以预测多种癌症之间共享的核心癌症基因,以期阐明常见的癌症机制。我们的策略使用了两种多任务学习算法,一种用于特征选择,另一种用于验证所选特征。两种方法的结合使用可以产生更稳健的分类器和更可靠的选择特征。选择了前 73 个显著特征,映射到 72 个基因,作为核心癌症基因。在对独立测试数据进行的盲测中,进一步证明了这 73 个特征的有效性。使用系统生物学分析评估这些基因的生物学意义。广泛的功能、途径和网络分析证实了先前研究中的发现,并为常见的癌症机制提供了新的见解。我们的策略可以用作在基因组水平上从大型基因表达数据集中找到重要基因的一般方法。所选基因可用于预测癌症。

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