Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes.
Single molecule-level detection and long read-based phasing of epigenetic variations in bacterial methylomes.
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DOI：
10.1038/ncomms8438
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发表时间：
2015-06-15
影响因子：
16.6
通讯作者：
Fang, Gang
中科院分区：
文献类型：
--
作者：
Beaulaurier, John;Zhang, Xue-Song;Zhu, Shijia;Sebra, Robert;Rosenbluh, Chaggai;Deikus, Gintaras;Shen, Nan;Munera, Diana;Waldor, Matthew K.;Chess, Andrew;Blaser, Martin J.;Schadt, Eric E.;Fang, Gang
除了在宿主防御中的作用外，细菌DNA甲基化还在基因表达、毒力和抗生素抗性的调节中发挥重要作用。克隆群体中的细菌细胞可以产生表观遗传异质性以增加群体水平的表型可塑性。单分子实时（SMRT）测序能够检测N6-甲基腺嘌呤和N4-甲基胞嘧啶，这两种主要类型的DNA修饰构成细菌甲基化组。然而，现有的基于SMRT测序的研究细菌甲基化组的方法依赖于群体水平的共识，缺乏观察表观遗传异质性所需的单细胞分辨率。在这里，我们提出了SMALR（长读段的单分子修饰分析），这是一种用于单分子水平检测和DNA甲基化定相的新框架。使用七个细菌菌株，我们表明，SMALR产量显着提高分辨率，并揭示了不同类型的表观遗传异质性。SMALR是一种功能强大的新工具，能够从头检测表观遗传异质性，并使其在细菌种群中的功能研究成为可能。 细菌DNA甲基化涉及从宿主防御到抗生素抗性的许多过程，然而目前用于检查甲基化基因组的方法缺乏单细胞分辨率。在这里，Beaulaurier等人提出了长读数的单分子修饰分析，这是一种用于从头检测表观遗传异质性的新工具。
Beyond its role in host defense, bacterial DNA methylation also plays important roles in the regulation of gene expression, virulence and antibiotic resistance. Bacterial cells in a clonal population can generate epigenetic heterogeneity to increase population-level phenotypic plasticity. Single molecule, real-time (SMRT) sequencing enables the detection of N6-methyladenine and N4-methylcytosine, two major types of DNA modifications comprising the bacterial methylome. However, existing SMRT sequencing-based methods for studying bacterial methylomes rely on a population-level consensus that lacks the single-cell resolution required to observe epigenetic heterogeneity. Here, we present SMALR (single-molecule modification analysis of long reads), a novel framework for single molecule-level detection and phasing of DNA methylation. Using seven bacterial strains, we show that SMALR yields significantly improved resolution and reveals distinct types of epigenetic heterogeneity. SMALR is a powerful new tool that enables de novo detection of epigenetic heterogeneity and empowers investigation of its functions in bacterial populations. Bacterial DNA methylation is involved in many processes, from host defense to antibiotic resistance, however current methods for examining methylated genomes lack single-cell resolution. Here Beaulaurier et al. present Single Molecule Modification Analysis of Long Reads, a new tool for de novo detection of epigenetic heterogeneity.
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影响因子：
4.5
作者：
Furuta Y;Namba-Fukuyo H;Shibata TF;Nishiyama T;Shigenobu S;Suzuki Y;Sugano S;Hasebe M;Kobayashi I
通讯作者：
Kobayashi I
影响因子：
48
作者：
Flusberg, Benjamin A.;Webster, Dale R.;Lee, Jessica H.;Travers, Kevin J.;Olivares, Eric C.;Clark, Tyson A.;Korlach, Jonas;Turner, Stephen W.
通讯作者：
Turner, Stephen W.
影响因子：
4.3
作者：
Feng Z;Fang G;Korlach J;Clark T;Luong K;Zhang X;Wong W;Schadt E
通讯作者：
Schadt E
影响因子：
4.9
作者：
Jen, Freda E. -C.;Seib, Kate L.;Jennings, Michael P.
通讯作者：
Jennings, Michael P.
影响因子：
3.2
作者：
Bendall, Matthew L.;Luong, Khai;Malmstrom, Rex R.
通讯作者：
Malmstrom, Rex R.