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利用纳米孔测序检测 DNA 胞嘧啶甲基化。

Detecting DNA cytosine methylation using nanopore sequencing.

机构信息

Ontario Institute for Cancer Research, Toronto, Ontario, Canada.

Department of Computer Science, University of Toronto, Toronto, Ontario, Canada.

出版信息

Nat Methods. 2017 Apr;14(4):407-410. doi: 10.1038/nmeth.4184. Epub 2017 Feb 20.

Abstract

In nanopore sequencing devices, electrolytic current signals are sensitive to base modifications, such as 5-methylcytosine (5-mC). Here we quantified the strength of this effect for the Oxford Nanopore Technologies MinION sequencer. By using synthetically methylated DNA, we were able to train a hidden Markov model to distinguish 5-mC from unmethylated cytosine. We applied our method to sequence the methylome of human DNA, without requiring special steps for library preparation.

摘要

在纳米孔测序设备中,电流信号对碱基修饰很敏感,如 5-甲基胞嘧啶(5-mC)。在这里,我们量化了 Oxford Nanopore Technologies MinION 测序仪对此效应的敏感程度。通过使用合成的甲基化 DNA,我们成功训练了一个隐马尔可夫模型,能够区分 5-mC 和未甲基化的胞嘧啶。我们将该方法应用于人类 DNA 的甲基化组测序,而无需进行特殊的文库制备步骤。

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