Combination of Single-Molecule Electrical Measurements and Machine Learning for the Identification of Single Biomolecules.

Masateru Taniguchi

doi:10.1021/acsomega.9b03660

Abstract

The development of a next-generation DNA sequencer has provided a method for electrically measuring single molecules. Methods for electrically measuring one molecule are roughly divided into methods for measuring tunneling and ion currents. These methods enable identification of a single molecule of DNA, a RNA nucleotide, or a single protein based on current histograms. However, overlapping of current histograms of molecules with similar properties has been a major barrier to identifying single molecules with high accuracy. This barrier was broken by introducing machine learning. Combining single-molecule electrical measurement and machine learning enables high-precision identification of single molecules. Highly accurate discrimination has been demonstrated for DNA nucleotides, RNA nucleotides, amino acids, sugars, viruses, and bacteria. This combination enables quantitative evaluation of molecular recognition ability. Furthermore, a device structure suitable for high-precision identification has been designed. Combining single-molecule electrical measurement with machine learning enables digital analytical chemistry that can count certain types of molecules. Digital analytical chemistry enables comprehensive analysis of chemical reactions. This new analytical method will lead to the discovery of unknown or missed valuable molecules.

Highlights

Disease prevention is an important global issue
It is effective to examine a small number of viruses and bacteria before these multiply in the body
This is because on-site measurements can be transferred to a server and analyzed using a smartphone and the inspection results returned to the hand

Summary

■ INTRODUCTION

Disease prevention is an important global issue. To achieve this, diseases, including infectious diseases, must be quickly, cheaply, and accurately diagnosed at an early stage. A method of examining a small number, ideally a single DNA molecule, virus, or bacterium, is desirable for early diagnosis. Optical methods such as real-time polymerase chain reaction (RT-PCR) and enzyme-linked immune sorbent assay (ELISA) have been used to test for diseases, including infectious diseases. The tunneling current−time waveform is characterized by a maximum current (IpT) and a current duration (tdT).[4] Two or more analytes are identified by an IpT or tdT histogram or an IpT−tdT heat map This method has been widely applied to DNA and RNA sequencing, peptide amino acid sequencing, and identification of modified and unmodified amino acid molecules.[4].

ACS Omega

Findings

■ REFERENCES