Region-Specific Methylation Profiling in Acute Myeloid Leukemia.
Region-Specific Methylation Profiling in Acute Myeloid Leukemia.
复制标题
DOI：
10.1007/s12539-018-0285-4
复制
发表时间：
2018-03
期刊：
影响因子：
--
通讯作者：
Polanska J
中科院分区：
文献类型：
--
作者：
Cecotka A;Polanska J
肿瘤疾病中DNA甲基化水平的改变导致基因表达的失调--抑癌基因的沉默和原癌基因的增强。有几种工具致力于识别CpG位点的去甲基化问题，但它们中的大多数集中在单个位点水平，并且不允许定量区域甲基化变化。目的是创建一种自适应算法，支持检测急性髓性白血病特异性的差异甲基化CpG位点和基因组区域。了解AML甲基化指纹有助于更好地理解白血病发生的表观遗传学。提出的算法是数据驱动的，不使用预定义的量化阈值。高斯混合建模支持CpG位点的分类到几个去甲基化水平。p值整合允许从单位点去甲基化翻译为基因启动子和体区域的去甲基化。检查了健康对照和AML患者的甲基化谱（GEO：GSE 63409）。观察到全基因组甲基化谱的差异。甲基化谱在基因组区域之间显著不同。启动子区域的甲基化水平最低，而基因间区域的甲基化水平平均较高。观察到的AML相关甲基化位点减少的数量并未偶然地显著超过预期数量。基因间区域的特征是AML甲基化位点的最高百分比。基因间区甲基化增强/减少最常见，而启动子区甲基化补偿（阳性或阴性）是特异性的。对AML低甲基化或极高甲基化基因进行的功能分析显示与白血病过程有很强的联系。本文的在线版本（10.1007/s12539-018-0285-4）包含补充材料，可供授权用户使用。
Alteration of DNA methylation level in cancer diseases leads to deregulation of gene expression—silencing of tumor suppressor genes and enhancing of protooncogenes. There are several tools devoted to the problem of identification of CpG sites' demethylation but majority of them focuses on single site level and does not allow for quantification of region methylation changes. The aim was to create an adaptive algorithm supporting detection of differentially methylated CpG sites and genomic regions specific for acute myeloid leukemia. Knowledge on AML methylation fingerprint helps in better understanding the epigenetics of leukemogenesis. Proposed algorithm is data driven and does not use predefined quantification thresholds. Gaussian mixture modeling supports classification of CpG sites to several levels of demethylation. p value integration allows for translation from single site demethylation to the demethylation of gene promoter and body regions. Methylation profiles of healthy controls and AML patients were examined (GEO:GSE63409). The differences in whole genome methylation profiles were observed. The methylation profile differs significantly among genomic regions. The lowest methylation level was observed for promoter regions, while sites from intergenic regions were by average higher methylated. The observed number of AML related down methylated sites has not substantially exceeded the expected number by chance. Intergenic regions were characterized by the highest percentage of AML up methylated sites. Methylation enhancement/diminution is the most frequent for intergenic region while methylation compensation (positive or negative) is specific for promoter regions. Functional analysis performed for AML down methylated or extreme high up methylated genes showed strong connection to the leukemic processes. The online version of this article (10.1007/s12539-018-0285-4) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
7
作者：
Harrow J;Frankish A;Gonzalez JM;Tapanari E;Diekhans M;Kokocinski F;Aken BL;Barrell D;Zadissa A;Searle S;Barnes I;Bignell A;Boychenko V;Hunt T;Kay M;Mukherjee G;Rajan J;Despacio-Reyes G;Saunders G;Steward C;Harte R;Lin M;Howald C;Tanzer A;Derrien T;Chrast J;Walters N;Balasubramanian S;Pei B;Tress M;Rodriguez JM;Ezkurdia I;van Baren J;Brent M;Haussler D;Kellis M;Valencia A;Reymond A;Gerstein M;Guigó R;Hubbard TJ
通讯作者：
Hubbard TJ
影响因子：
4.8
作者：
DICE, LR
通讯作者：
DICE, LR
影响因子：
5.8
作者：
Aryee, Martin J.;Jaffe, Andrew E.;Irizarry, Rafael A.
通讯作者：
Irizarry, Rafael A.
影响因子：
2.6
作者：
Garrido, SM;Appelbaum, FR;Banker, DE
通讯作者：
Banker, DE
影响因子：
14.9
作者：
Casper J;Zweig AS;Villarreal C;Tyner C;Speir ML;Rosenbloom KR;Raney BJ;Lee CM;Lee BT;Karolchik D;Hinrichs AS;Haeussler M;Guruvadoo L;Navarro Gonzalez J;Gibson D;Fiddes IT;Eisenhart C;Diekhans M;Clawson H;Barber GP;Armstrong J;Haussler D;Kuhn RM;Kent WJ
通讯作者：
Kent WJ