Machine Learning to Improve the Sensing of Biomolecules by Conical Track-Etched Nanopore.

Nathan Meyer,Jean-Marc Janot,Mathilde Lepoitevin,Michaël Smietana,Joan Torrent,Sébastien Balme,Jean-Jacques Vasseur

doi:10.3390/bios10100140

Abstract

Single nanopore is a powerful platform to detect, discriminate and identify biomacromolecules. Among the different devices, the conical nanopores obtained by the track-etched technique on a polymer film are stable and easy to functionalize. However, these advantages are hampered by their high aspect ratio that avoids the discrimination of similar samples. Using machine learning, we demonstrate an improved resolution so that it can identify short single- and double-stranded DNA (10- and 40-mers). We have characterized each current blockade event by the relative intensity, dwell time, surface area and both the right and left slope. We show an overlap of the relative current blockade amplitudes and dwell time distributions that prevents their identification. We define the different parameters that characterize the events as features and the type of DNA sample as the target. By applying support-vector machines to discriminate each sample, we show accuracy between 50% and 72% by using two features that distinctly classify the data points. Finally, we achieved an increased accuracy (up to 82%) when five features were implemented.

Highlights

For the past three decades, single nanopore technology have emerged as single-molecule sensors and offer many practical uses such as long read DNA sequencing [1,2]
Polymer nanopore obtained by the track-etched technique provided a long high-aspect-ratio nanochannel [15,16]
We addressed the hypothesis that machine learning, in conjunction with the careful choice of multiple parameters that allow for characterizing the current blockade events, could improve the accuracy of

Summary

Introduction

For the past three decades, single nanopore technology have emerged as single-molecule sensors and offer many practical uses such as long read DNA sequencing [1,2]. This was achieved by engineering biological nanopores combined with biological machines to control the DNA translocation speed [3,4,5,6,7]. Thin films of semiconductors (SiN) drilled by transmission electron microscopy or focused ion beam were used to provide nanopores with a low aspect ratio [13,14]. Polymer nanopore obtained by the track-etched technique provided a long high-aspect-ratio nanochannel [15,16]

Objectives

Methods

Results