Mapping Base Modifications in DNA by Transverse-Current Sequencing
Mapping Base Modifications in DNA by Transverse-Current Sequencing
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DOI：
10.1103/physrevapplied.9.024024
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发表时间：
2018-02-23
影响因子：
4.6
通讯作者：
Velev, Julian P.
中科院分区：
文献类型：
--
作者：
Alvarez, Jose R.;Skachkov, Dmitry;Velev, Julian P.
测序DNA修饰和损伤，如胞嘧啶的甲基化和鸟嘌呤的氧化，甚至比测序基因组本身更重要和更具挑战性。用于检测DNA修饰的传统方法要么对这些修饰不敏感，要么需要额外的处理步骤来鉴定特定类型的修饰。纳米孔中的横向电流测序可以潜在地在同一运行中鉴定典型碱基和碱基修饰。在这项工作中，我们证明了最常见的DNA表观遗传修饰和病变可以根据其隧道电流签名以任何预定义的准确度进行检测。我们的研究结果是基于模拟的纳米孔隧道电流通过DNA分子，计算使用非平衡电子传输方法在一个有效的多轨道模型来自第一原理计算，其次是一个基地调用算法占邻居电流电流的相关性。这种方法可以与现有的实验技术相结合，以提高碱基识别的保真度。
Sequencing DNA modifications and lesions, such as methylation of cytosine and oxidation of guanine, is even more important and challenging than sequencing the genome itself. The traditional methods for detecting DNA modifications are either insensitive to these modifications or require additional processing steps to identify a particular type of modification. Transverse-current sequencing in nanopores can potentially identify the canonical bases and base modifications in the same run. In this work, we demonstrate that the most common DNA epigenetic modifications and lesions can be detected with any predefined accuracy based on their tunneling current signature. Our results are based on simulations of the nanopore tunneling current through DNA molecules, calculated using nonequilibrium electron-transport methodology within an effective multiorbital model derived from first-principles calculations, followed by a base-calling algorithm accounting for neighbor current-current correlations. This methodology can be integrated with existing experimental techniques to improve base-calling fidelity.