MOSAIC: A Modular Single Molecular Analysis Interface for Decoding Multi-state Nanopore Data

Published: October 31, 2016

Author(s)

Jacob H. Forstater, Kyle Briggs, Joseph W. Robertson, Jessica H. Benjamini, Olivier M. Marie-Rose, Canute I. Vaz, John J. Kasianowicz, Vincent Tabard-Cossa, Arvind K. Balijepalli

Abstract

Single molecule measurements with nanometer-scale pores are being developed for a wide range of diagnostic and therapeutic applications.  Critical to the method is the ability to accurately and precisely detect the presence of an analyte, quantify its interaction with the pore, and determine its residence time. We have developed an open source program called MOSAIC that considerably improves the accuracy and throughput of the data analysis over existing techniques, when applied to single-molecule measurements made with protein or solid-state nanopores. MOSAIC consists of two key algorithms – ADEPT, which uses a physical model of the nanopore to characterize short transient events that do not reach their steady state amplitude, and CUSUM+, a version of the cumulative sum algorithm, optimized for the analysis of events with long residence times. Working in concert, the algorithms within MOSAIC allowed us to observe new transitional states associated with the stretching of double-stranded DNA within a solid-state nanopore, and new interaction modes between a 20-mer of single-stranded DNA and a Staphylococcus aureus -hemolysin (HL) nanopore. Finally, we demonstrate the ease of using MOSAIC to obtain a quantitative analysis of synthetic polymers measured with an αHL nanopore.
Citation: Analytical Chemistry
Volume: 88
Pub Type: Journals

Keywords

solid-state nanopores, biological nanopores, analysis software, DNA, proteins, single molecule measurements, MOSAIC
Created October 31, 2016, Updated November 10, 2018