Physical Measurement Laboratory, National Institute of Standards and Technology , Gaithersburg, Maryland 20899, United States.
Department of Chemical Engineering, Columbia University , New York, New York 10027, United States.
Anal Chem. 2016 Dec 6;88(23):11900-11907. doi: 10.1021/acs.analchem.6b03725. Epub 2016 Nov 15.
Biological and solid-state nanometer-scale pores are the basis for numerous emerging analytical technologies for use in precision medicine. We developed Modular Single-Molecule Analysis Interface (MOSAIC), an open source analysis software that improves the accuracy and throughput of nanopore-based measurements. Two key algorithms are implemented: ADEPT, which uses a physical model of the nanopore system to characterize short-lived events that do not reach their steady-state current, and CUSUM+, a version of the cumulative sum statistical method optimized for longer events that do. We show that ADEPT detects previously unreported conductance states that occur as double-stranded DNA translocates through a 2.4 nm solid-state nanopore and reveals new interactions between short single-stranded DNA and the vestibule of a biological pore. These findings demonstrate the utility of MOSAIC and the ADEPT algorithm, and offer a new tool that can improve the analysis of nanopore-based measurements.
生物和固态纳米级孔是许多新兴分析技术的基础，这些技术可用于精准医疗。我们开发了模块化单分子分析接口 (MOSAIC)，这是一款开源分析软件，可提高基于纳米孔的测量的准确性和吞吐量。我们实现了两个关键算法：ADEPT，它使用纳米孔系统的物理模型来描述未达到稳定电流的短寿命事件；CUSUM+，这是一种针对较长事件优化的累积和统计方法。我们表明，ADEPT 可以检测到以前未报告的电导状态，这些状态发生在双链 DNA 通过 2.4nm 固态纳米孔时，并揭示了短单链 DNA 与生物孔前庭之间的新相互作用。这些发现证明了 MOSAIC 和 ADEPT 算法的实用性，并提供了一种可以改进基于纳米孔的测量分析的新工具。
