本文關鍵詞： 差異甲基化檢驗 亞硫酸氫鹽測序 功能富集分析　出處：《復旦學報(自然科學版)》2017年06期 　論文類型：期刊論文

【摘要】：DNA甲基化是一種重要的表觀遺傳學修飾,能夠參與基因表達調(diào)控從而影響生理活動.在病例-對照組研究中,利用甲基化水平定位與疾病相關聯(lián)的基因功能區(qū)域,有助于了解甲基化調(diào)控基因表達的機制,為后續(xù)研究提供疾病關聯(lián)基因的線索.目前檢驗甲基化差異區(qū)域的方法存在一定不足:一是缺乏定義差異甲基化區(qū)域的統(tǒng)一標準;二是檢測結(jié)果存在橫跨多個基因功能區(qū)域的現(xiàn)象,難以進行生物學解釋.本文基于得分檢驗(Zscore test)提出了以基因功能區(qū)域為單位的檢驗差異甲基化水平的方法cZST.該方法的特點是依靠位點物理距離和染色體全局信息修正協(xié)方差矩陣.模擬研究表明cZST在亞硫酸氫鹽測序數(shù)據(jù)樣本量小、讀數(shù)低、擾動位點多的情形下具有高功效,且優(yōu)于現(xiàn)有方法.將cZST運用到乳腺導管癌真實數(shù)據(jù)中,檢測出與疾病顯著相關的661個基因功能區(qū)和81個單位點.基因注釋分析說明了cZST方法的有效性,并發(fā)現(xiàn)Dbl、Pleckstrin基因家族及Rho調(diào)控基因的甲基化與乳腺導管癌緊密相關,為后續(xù)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.
【作者單位】： 復旦大學生命科學學院生物統(tǒng)計學與計算生物學系;
【基金】：國家自然科學基金(11571082,11171075)
【分類號】：R440
【正文快照】： DNA甲基化是發(fā)生在生物DNA鏈核苷酸上的一種化學修飾.在真核細胞中,S-腺苷甲硫氨酸上的甲基會在DNA甲基轉(zhuǎn)移酶的作用下,轉(zhuǎn)移到DNA分子CpG序列的胞嘧啶上[1].人類DNA中約70%~90%CpG二核苷酸存在甲基化修飾[2],并且甲基化的CpG二核苷酸大部分聚集在基因的5’端,稱為CpG島,長度在

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