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research article

Detecting topological variations of DNA at single-molecule level

Liu, Ke  
•
Pan, Chao
•
Kühn, Alexandre
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2019
Nature Communications

In addition to their use in DNA sequencing, ultrathin nanopore membranes have potential applications in detecting topological variations in deoxyribonucleic acid (DNA). This is due to the fact that when topologically edited DNA molecules, driven by electrophoretic forces, translocate through a narrow orifice, transient residings of edited segments inside the orifice modulate the ionic flow. Here we utilize two programmable barcoding methods based on base-pairing, namely forming a gap in dsDNA and creating protrusion sites in ssDNA for generating a hybrid DNA complex. We integrate a discriminative noise analysis for ds and ss DNA topologies into the threshold detection, resulting in improved multi-level signal detection and consequent extraction of reliable information about topological variations. Moreover, the positional information of the barcode along the template sequence can be determined unambiguously. All methods may be further modified to detect nicks in DNA, and thereby detect DNA damage and repair sites.

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Type
research article
DOI
10.1038/s41467-018-07924-1
Author(s)
Liu, Ke  
Pan, Chao
Kühn, Alexandre
Nievergelt, Adrian Pascal  
Fantner, Georg  
Milenkovic, Olgica
Radenovic, Aleksandra  
Date Issued

2019

Publisher

Nature Research

Published in
Nature Communications
Volume

10

Start page

3

Note

This is an open access article under the terms of the Creative Commons Attribution License.

Editorial or Peer reviewed

REVIEWED

Written at

EPFL

EPFL units
LBNI  
LBEN  
Available on Infoscience
January 18, 2019
Use this identifier to reference this record
https://infoscience.epfl.ch/handle/20.500.14299/153524
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