Reducing error rates in third-generation sequencing technology

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.


Transverse current setup for a single strand DNA or RNA molecule translocating through a nanopore between a pair of tapered metal electrodes. In the corresponding linear chain model each nucleotide is represented by a site (color dashed line rectangles). The quantities hXi and VXiXj represent the Hamiltonian of an isolated site and the interaction between neighboring sites. The coupling of a nucleotide with the right/left electrode are represented by t(R/L)X .

Here, researchers from the University of Puerto Rico San Juan 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. They 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.

Alvarez JR, Skachkov D, Massey SE, Kalitsov A, Velev JP. (2015) DNA/RNA transverse current sequencing: intrinsic structural noise from neighboring bases. Front Genet 6:213. [abstract]

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