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Front Genet. 2015 Jun 19;6:213. doi: 10.3389/fgene.2015.00213. eCollection 2015.

DNA/RNA transverse current sequencing: intrinsic structural noise from neighboring bases.

Frontiers in genetics

Jose R Alvarez, Dmitry Skachkov, Steven E Massey, Alan Kalitsov, Julian P Velev

Affiliations

  1. Department of Physics, University of Puerto Rico San Juan, PR, USA.
  2. Department of Biology, University of Puerto Rico San Juan, PR, USA.
  3. Department of Physics, University of Puerto Rico San Juan, PR, USA ; Department of Physics, University of Nebraska Lincoln, NE, USA ; Université Grenoble Alpes/CNRS/CEA, INAC-SPINTEC Grenoble, France.

PMID: 26150827 PMCID: PMC4473640 DOI: 10.3389/fgene.2015.00213

Abstract

Nanopore DNA sequencing via transverse current has emerged as a promising candidate for third-generation sequencing technology. It produces long read lengths which could alleviate problems with assembly errors inherent in current technologies. However, the high error rates of nanopore sequencing have to be addressed. A very important source of the error is the intrinsic noise in the current arising from carrier dispersion along the chain of the molecule, i.e., from the influence of neighboring bases. In this work we perform calculations of the transverse current within an effective multi-orbital tight-binding model derived from first-principles calculations of the DNA/RNA molecules, to study the effect of this structural noise on the error rates in DNA/RNA sequencing via transverse current in nanopores. We demonstrate that a statistical technique, utilizing not only the currents through the nucleotides but also the correlations in the currents, can in principle reduce the error rate below any desired precision.

Keywords: DNA; RNA; nanopore sequencing; third-generation sequencing; transverse current

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