基于病例对照组的检验差异甲基化基因功能区域的方法

发布时间：2018-01-22 04:16

本文关键词： 差异甲基化检验亚硫酸氢盐测序功能富集分析　出处：《复旦学报(自然科学版)》2017年06期 　论文类型：期刊论文

【摘要】：DNA甲基化是一种重要的表观遗传学修饰,能够参与基因表达调控从而影响生理活动.在病例-对照组研究中,利用甲基化水平定位与疾病相关联的基因功能区域,有助于了解甲基化调控基因表达的机制,为后续研究提供疾病关联基因的线索.目前检验甲基化差异区域的方法存在一定不足:一是缺乏定义差异甲基化区域的统一标准;二是检测结果存在横跨多个基因功能区域的现象,难以进行生物学解释.本文基于得分检验(Zscore test)提出了以基因功能区域为单位的检验差异甲基化水平的方法cZST.该方法的特点是依靠位点物理距离和染色体全局信息修正协方差矩阵.模拟研究表明cZST在亚硫酸氢盐测序数据样本量小、读数低、扰动位点多的情形下具有高功效,且优于现有方法.将cZST运用到乳腺导管癌真实数据中,检测出与疾病显著相关的661个基因功能区和81个单位点.基因注释分析说明了cZST方法的有效性,并发现Dbl、Pleckstrin基因家族及Rho调控基因的甲基化与乳腺导管癌紧密相关,为后续研究提供指引.
[Abstract]:DNA methylation is an important epigenetic modification that participates in the regulation of gene expression and thus affects physiological activities. It is helpful to understand the mechanism of methylation regulating gene expression by using methylation level to locate the functional regions of genes associated with disease. To provide clues of disease related genes for further research. There are some deficiencies in the current methods of testing methylation differential regions: first, there is a lack of uniform standards for defining differential methylation regions; Second, the results of the detection across multiple gene functional regions of the phenomenon. It is difficult to interpret biology. This article is based on the score test. A method of testing differential methylation level based on functional region of gene cZST is proposed. The characteristic of this method is to modify covariance matrix based on physical distance of locus and global information of chromosome. Simulation results show that cZ. The sample size of St in the hydrogen sulfite sequencing data was small. Low readings and multiple disturbed sites are highly effective and superior to existing methods. CZST is applied to the real data of breast ductal carcinoma. A total of 661 gene functional regions and 81 unit sites were detected which were significantly related to the disease. Gene annotation analysis showed the effectiveness of the cZST method and found Dbl. Methylation of Pleckstrin gene family and Rho regulatory gene is closely related to breast ductal carcinoma.
【作者单位】：复旦大学生命科学学院生物统计学与计算生物学系;
【基金】：国家自然科学基金(11571082,11171075)
【分类号】：R440
【正文快照】： DNA甲基化是发生在生物DNA链核苷酸上的一种化学修饰.在真核细胞中,S-腺苷甲硫氨酸上的甲基会在DNA甲基转移酶的作用下,转移到DNA分子CpG序列的胞嘧啶上[1].人类DNA中约70%~90%CpG二核苷酸存在甲基化修饰[2],并且甲基化的CpG二核苷酸大部分聚集在基因的5’端,称为CpG岛,长度在

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