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Identifying hypermethylated CpG islands using a quantile regression model

机译:使用分位数回归模型识别超甲基化的CpG岛

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摘要

BackgroundDNA methylation has been shown to play an important role in the silencing of tumor suppressor genes in various tumor types. In order to have a system-wide understanding of the methylation changes that occur in tumors, we have developed a differential methylation hybridization (DMH) protocol that can simultaneously assay the methylation status of all known CpG islands (CGIs) using microarray technologies. A large percentage of signals obtained from microarrays can be attributed to various measurable and unmeasurable confounding factors unrelated to the biological question at hand. In order to correct the bias due to noise, we first implemented a quantile regression model, with a quantile level equal to 75%, to identify hypermethylated CGIs in an earlier work. As a proof of concept, we applied this model to methylation microarray data generated from breast cancer cell lines. However, we were unsure whether 75% was the best quantile level for identifying hypermethylated CGIs. In this paper, we attempt to determine which quantile level should be used to identify hypermethylated CGIs and their associated genes.
机译:背景DNA已显示出甲基化在各种肿瘤类型的抑癌基因沉默中起重要作用。为了对肿瘤中发生的甲基化变化有一个全系统的了解,我们开发了一种差异甲基化杂交(DMH)方案,可以使用微阵列技术同时测定所有已知CpG岛(CGI)的甲基化状态。从微阵列获得的信号的很大一部分可归因于与手头生物学问题无关的各种可测量和不可测量的混杂因素。为了纠正由于噪声引起的偏差,我们在较早的工作中首先实现了分位数回归模型(分位数水平等于75%)来识别超甲基化的CGI。作为概念的证明,我们将此模型应用于从乳腺癌细胞系产生的甲基化微阵列数据。但是,我们不确定是否有75%是识别高甲基化CGI的最佳分位数。在本文中,我们尝试确定应使用哪个分位数来识别超甲基化的CGI及其相关基因。

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