固态纳米孔电流迹线中多级易位事件分析

Xinlong Liu, Zepeng Sun, W. Liu, Feng Qiao, Li Cui, Jing Yang, Jingjie Sha, Jian Li, Li-Qun Xu
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引用次数: 1

摘要

固体纳米孔在生物分子构象检测、生物标志物鉴定和蛋白质指纹图谱等测序研究中表现出了令人印象深刻的性能。在所有这些场景中,准确的事件检测是数据分析的基本步骤。大多数现有的事件检测方法使用用户定义的阈值或由数据自动确定的自适应阈值。前一类严重依赖人力专业知识,这是劳动密集型的;后者似乎更高级,然而,阈值参数的设置有些棘手。因此,不同方法的结果往往不一致。在本文中,我们开发了一种新的事件检测方法,其中选择阈值的计算遵循由解析表达式支配的原则。与其他方法不同的是,每个事件的起始点和结束点都是基于斜率来定位的,而不是选择当前值越过基线的第一个点。此外,我们还添加了一个方法来确定每个事件中是否存在多个级别。然后,我们分别在两组由短ssDNA和48.5kb λ-DNA样本产生的电流迹上对该方法进行了评估。结果表明,我们的方法在检测相对较低振幅的挑战性易位事件上表现良好,并且能够准确定位每个级别事件的开始/结束点。
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Multi-level translocation events analysis in solid-state nanopore current traces
Solid-state nanopores have shown impressive performances in several sequencing research scenarios, such as biomolecule conformation detection, biomarker identification, and protein fingerprinting. In all these scenarios, accurate event detection is the fundamental step toward data analysis. Most existing event detection methods use either user-defined thresholds or adaptive thresholds determined automatically by the data. The former class depends heavily on human expertise, which is labor-intensive; the latter appears to be more advanced, however, the setting of threshold parameters is somewhat tricky. Hence, the results are usually inconsistent among different methods. In this paper, we develop a novel event detection method, where the selection threshold is computed following the principle governed by an analytical expression. Unlike other methods, each event’s starting and ending points are located based on the slope rather than picking the first point whose current value goes across the baseline. Moreover, we add a method to determine whether multiple levels are present within each event. We then evaluate the method on two groups of current traces generated by short ssDNA and 48.5kb λ-DNA samples, respectively. The results show that our method performs well on detecting challenging translocation events with relatively low amplitudes, and is also able to accurately locate the starting/end points of each level of the events.
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