Targeted bisulfite sequencing of the dynamic DNA methylome.
Targeted bisulfite sequencing of the dynamic DNA methylome.
复制标题
DOI：
10.1186/s13072-016-0105-1
复制
发表时间：
2016
影响因子：
3.9
通讯作者：
Meissner A
中科院分区：
文献类型：
--
作者：
Ziller MJ;Stamenova EK;Gu H;Gnirke A;Meissner A
精确有效地测量DNA甲基化的能力继续推动我们对发育和疾病中这种修饰的理解。全基因组亚硫酸氢盐测序具有理论上以单核苷酸分辨率捕获基因组中所有胞嘧啶的优点，但它具有随着样品数量增加而放大的许多显著的实际缺点。所有其他技术仅捕获一小部分在细胞和组织类型中显示动态调节的胞嘧啶。在这里，我们提出了一种新的杂交选择设计，重点是动态甲基化的基因座，捕获了大量的差异甲基化的基因调控元件。我们以匹配的全基因组数据为基准，对25个人体组织样本进行了分析，以探索其检测差异甲基化区域的能力。我们的目标捕获设计填补了所有其他存在的DNA甲基化图谱分析留下的主要空白。它保持了将胞嘧啶甲基化与遗传差异、单碱基分辨率和相邻胞嘧啶分析联系起来的能力，同时通过将测序工作集中在基因组中信息量最大和最相关的区域，显著降低了每个样本的成本。本文的在线版本（doi：10.1186/s13072-016-0105-1）包含补充材料，可供授权用户使用。
The ability to measure DNA methylation precisely and efficiently continues to drive our understanding of this modification in development and disease. Whole genome bisulfite sequencing has the advantage of theoretically capturing all cytosines in the genome at single-nucleotide resolution, but it has a number of significant practical drawbacks that become amplified with increasing sample numbers. All other technologies capture only a fraction of the cytosines that show dynamic regulation across cell and tissue types. Here, we present a novel hybrid selection design focusing on loci with dynamic methylation that captures a large number of differentially methylated gene-regulatory elements. We benchmarked this assay against matched whole genome data and profiled 25 human tissue samples to explore its ability to detect differentially methylated regions. Our target capture design fills a major gap left by all other assays that exist to map DNA methylation. It maintains the ability to link cytosine methylation to genetic differences, the single-base resolution and the analysis of neighboring cytosines while notably reducing the cost per sample by focusing the sequencing effort on the most informative and relevant regions of the genome. The online version of this article (doi:10.1186/s13072-016-0105-1) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
14.9
作者：
Feng H;Conneely KN;Wu H
通讯作者：
Wu H
影响因子：
64.8
作者：
Schultz, Matthew D.;He, Yupeng;Whitaker, John W.;Hariharan, Manoj;Mukamel, Eran A.;Leung, Danny;Rajagopal, Nisha;Nery, Joseph R.;Urich, Mark A.;Chen, Huaming;Lin, Shin;Lin, Yiing;Jung, Inkyung;Schmitt, Anthony D.;Selvaraj, Siddarth;Ren, Bing;Sejnowski, Terrence J.;Wang, Wei;Ecker, Joseph R.
通讯作者：
Ecker, Joseph R.
影响因子：
64.5
作者：
Gifford CA;Ziller MJ;Gu H;Trapnell C;Donaghey J;Tsankov A;Shalek AK;Kelley DR;Shishkin AA;Issner R;Zhang X;Coyne M;Fostel JL;Holmes L;Meldrim J;Guttman M;Epstein C;Park H;Kohlbacher O;Rinn J;Gnirke A;Lander ES;Bernstein BE;Meissner A
通讯作者：
Meissner A
影响因子：
9.5
作者：
Thorvaldsdóttir H;Robinson JT;Mesirov JP
通讯作者：
Mesirov JP
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