De novo identification of differentially methylated regions in the human genome.
De novo identification of differentially methylated regions in the human genome.
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从头开始鉴定人基因组中差异甲基化区域。
DOI：
10.1186/1756-8935-8-6
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发表时间：
2015
影响因子：
3.9
通讯作者：
Molloy PL
中科院分区：
文献类型：
--
作者：
Peters TJ;Buckley MJ;Statham AL;Pidsley R;Samaras K;V Lord R;Clark SJ;Molloy PL
人类基因组中表型之间差异甲基化区域（DMR）的鉴定和表征是表观遗传学的主要兴趣。我们提出了一种新方法DMRcate，该方法使用高斯核在基因组空间上拟合来自Illumina HM 450 K BeadChip（或450 K阵列）的重复甲基化测量结果。DMRcate基于差异甲基化（DM）信号的可调核平滑来鉴定和排名基因组中最差异甲基化的区域。该方法对基因组注释和DM信号方向的局部变化都是不可知的，去除了由不规则间隔的甲基化位点引起的偏差，并通过与空模型的比较将显著性分配给每个DMR。我们表明，无论是模拟和真实的数据，DMRcate的预测性能上级Bumphunter和探针套索，并与梳-p的相称。对于真实的数据，我们验证所有阵列衍生的DMR从候选方法上的一套DMR来自全基因组亚硫酸氢盐测序呼吁从相同的DNA样本，使用两个单独的表型比较。基因组定位的单个甲基化位点聚集成离散DMR目前最好通过DM信号平滑和随后的阈值指定的组合来服务。研究结果还表明，450 K阵列的设计显示出对更可能差异甲基化的CpG位点的偏好，但其总体覆盖率并不能充分反映测序提供的甲基化特征的深度和复杂性。为了研究社区的方便，我们创建了一个用户友好的R软件包，称为DMRcate，可从Bioconductor下载，并与现有的预处理包兼容，它允许其他人在450 K阵列数据上应用相同的DMR查找方法。本文的在线版本（doi：10.1186/1756-8935-8-6）包含补充材料，可供授权用户使用。
The identification and characterisation of differentially methylated regions (DMRs) between phenotypes in the human genome is of prime interest in epigenetics. We present a novel method, DMRcate, that fits replicated methylation measurements from the Illumina HM450K BeadChip (or 450K array) spatially across the genome using a Gaussian kernel. DMRcate identifies and ranks the most differentially methylated regions across the genome based on tunable kernel smoothing of the differential methylation (DM) signal. The method is agnostic to both genomic annotation and local change in the direction of the DM signal, removes the bias incurred from irregularly spaced methylation sites, and assigns significance to each DMR called via comparison to a null model. We show that, for both simulated and real data, the predictive performance of DMRcate is superior to those of Bumphunter and Probe Lasso, and commensurate with that of comb-p. For the real data, we validate all array-derived DMRs from the candidate methods on a suite of DMRs derived from whole-genome bisulfite sequencing called from the same DNA samples, using two separate phenotype comparisons. The agglomeration of genomically localised individual methylation sites into discrete DMRs is currently best served by a combination of DM-signal smoothing and subsequent threshold specification. The findings also suggest the design of the 450K array shows preference for CpG sites that are more likely to be differentially methylated, but its overall coverage does not adequately reflect the depth and complexity of methylation signatures afforded by sequencing. For the convenience of the research community we have created a user-friendly R software package called DMRcate, downloadable from Bioconductor and compatible with existing preprocessing packages, which allows others to apply the same DMR-finding method on 450K array data. The online version of this article (doi:10.1186/1756-8935-8-6) contains supplementary material, which is available to authorized users.
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影响因子：
4.4
作者：
Bibikova, Marina;Barnes, Bret;Shen, Richard
通讯作者：
Shen, Richard
影响因子：
14.9
作者：
Feng H;Conneely KN;Wu H
通讯作者：
Wu H
在多因素全基因组亚硫酸盐测序实验中，使用β-二项式回归进行高精度差甲基化分析。
影响因子：
3
作者：
Dolzhenko E;Smith AD
通讯作者：
Smith AD
影响因子：
3.8
作者：
Dedeurwaerder, Sarah;Defrance, Matthieu;Fuks, Francois
通讯作者：
Fuks, Francois
影响因子：
12.3
作者：
Akalin A;Kormaksson M;Li S;Garrett-Bakelman FE;Figueroa ME;Melnick A;Mason CE
通讯作者：
Mason CE