Detection and Characterization of Single Cisplatin Adducts on DNA by Nanopore Sequencing

Xinjia Zhao; Yuru Liu; Xiaoyu Chen; Zhuang Mi; Wei Li; Pengye Wang; Xinyan Shan; Xinghua Lu

doi:10.1021/acsomega.1c02106

Detection and Characterization of Single Cisplatin Adducts on DNA by Nanopore Sequencing

ACS Omega. 2021 Jun 22;6(26):17027-17034. doi: 10.1021/acsomega.1c02106. eCollection 2021 Jul 6.

Authors

Xinjia Zhao^{1

2}, Yuru Liu¹, Xiaoyu Chen^{1

2}, Zhuang Mi^{1

2}, Wei Li¹, Pengye Wang^{1

2

3}, Xinyan Shan¹, Xinghua Lu^{1

2

4

3}

Affiliations

¹ Beijing National Laboratory for Condensed-Matter Physics and Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China.
² School of Physical Sciences, University of Chinese Academy of Sciences, Beijing 100190, China.
³ Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China.
⁴ Center for Excellence in Topological Quantum Computation, Chinese Academy of Sciences, Beijing 100190, China.

Abstract

Detection and characterization of an individual cisplatin adduct on a single DNA molecule is a demanding task. We explore the characteristic features of cisplatin adducts in the nanopore sequencing signal in aspects of dwell time, genome anchored current trace, and basecalling accuracy. The offset between the motor protein and the nanopore constriction region is revealed by dwell time analysis to be about 14 bases in the nanopore device as we examined. Characteristic distortions due to cisplatin adducts are illustrated in genome anchored current trace analysis, constituting the fingerprint for identification of cisplatin adduct. The sharp increase in odds ratio at the location of adducting sites provides additional feature in the detection of the adduct. By these combined methods, single cisplatin adducts can be detected with high fidelity on a single read of the DNA sequence. The study demonstrates an effective method in the detection and characterization of single cisplatin adducts on DNA at the single-molecule level and with single nucleotide spatial resolution.