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用于从DNA甲基化微阵列数据推断肿瘤纯度的通用信息性CpG位点。

Universal informative CpG sites for inferring tumor purity from DNA methylation microarray data.

作者信息

Dou Haixia, Fang Yun, Zheng Xiaoqi

机构信息

1 Department of Mathematics, Shanghai Normal University, Shanghai 200234, P. R. China.

出版信息

J Bioinform Comput Biol. 2018 Jun;16(3):1750030. doi: 10.1142/S0219720017500305. Epub 2017 Dec 28.

Abstract

Tumor purity is an intrinsic property of tumor samples and potentially has severe impact on many types of data analysis. We have previously developed a statistical method, InfiniumPurify, which could infer purity of a tumor sample given its tumor type (available in TCGA) or a set of informative CpG (iDMC) sites. However, in many clinical practices, researchers may focus on a specific type of tumor samples that is not included in TCGA, and samples which are too few to identify reliable iDMCs. This greatly restricts the application of InfiniumPurify in cancer research. In this paper, we proposed an updated version of InfiniumPurify (termed as uiInfiniumPurify) through identifying a universal set of iDMCs (uiDMCs) and redesigning the algorithm to determine hyper- and hypo-methylation status of each uiDMC. Through the application, we estimated tumor purities of 8830 tumor samples from TCGA. Result shows that our estimates are highly consistent with those by other available methods. Consequently, the updated uiInfiniumPurify, can be applied to a single sample (or a few samples) of interest whose tumor type is not included in TCGA. This characteristic will greatly broaden the application of uiInfiniumPurify in cancer research.

摘要

肿瘤纯度是肿瘤样本的一种内在属性,可能对多种类型的数据分析产生严重影响。我们之前开发了一种统计方法InfiniumPurify,它可以根据肿瘤样本的肿瘤类型(可从TCGA获取)或一组信息性CpG(iDMC)位点推断肿瘤样本的纯度。然而,在许多临床实践中,研究人员可能关注的是TCGA中未包含的特定类型的肿瘤样本,以及样本数量过少以至于无法识别可靠的iDMC的情况。这极大地限制了InfiniumPurify在癌症研究中的应用。在本文中,我们通过识别一组通用的iDMC(uiDMC)并重新设计算法来确定每个uiDMC的高甲基化和低甲基化状态,提出了InfiniumPurify的更新版本(称为uiInfiniumPurify)。通过应用,我们估计了来自TCGA的8830个肿瘤样本的肿瘤纯度。结果表明,我们的估计与其他现有方法的估计高度一致。因此,更新后的uiInfiniumPurify可应用于肿瘤类型未包含在TCGA中的单个感兴趣样本(或少数样本)。这一特性将极大地拓宽uiInfiniumPurify在癌症研究中的应用。

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