DNA sequencing using nanopores and kinetic proofreading

Abstract

We discuss the feasibility of using a nanopore sandwich device to implement the principle of kinetic proofreading to discriminate incorrect hybridizing oligonucleotides on a target DNA or RNA. We propose a method of sequencing DNA or RNA using this approach. The design parameters for such a DNA sequencer are estimated from the Hopfield-Ninio theory of kinetic proofreading and Schrödinger’s first-passage-time distribution function.

Graphical abstract

Keywords

DNA sequencing / nanopore sequencing / biosensing using kinetics

References

[1] Alberts, B., Bray, D., Hopkin, K., Johnson, A., Lewis, J., Raff, M., Roberts, K. and Walter, P. (2004), Molecular Biology of the Cell (2nd Ed.), pp.176. Garland Science Publishing

[2] Shusterman, R., Alon, S., Gavrinyov, T. and Krichevsky, O. (2004) Monomer dynamics in double- and single-stranded DNA polymers. Phys. Rev. Lett., 92, 048303

[3] Chi, Q., Wang, G. and Jiang, J. (2013) The persistence length and length per base of single-stranded DNA obtained from fluorescence correlation spectroscopy measurements using mean field theory. Physica A, 392, 1072–1079

[4] Sanger, F., Nicklen, S. and Coulson, A. R. (1977) DNA sequencing with chain-terminating inhibitors. Proc. Natl. Acad. Sci. USA, 74, 5463–5467

[5] Sanger, F, Coulson, A.R. (1978) The use of thin acrylamide gels for DNA sequencing. FEBS Lett., 87, 107–110

[6] Bentley, D. R., Balasubramanian, S., Swerdlow, H. P., Smith, G. P., Milton, J., Brown, C. G., Hall, K. P., Evers, D. J., Barnes, C. L., Bignell, H. R., (2008) Accurate whole human genome sequencing using reversible terminator chemistry. Nature, 456, 53–59

[7] Margulies, M., Egholm, M., Altman, W. E., Attiya, S., Bader, J. S., Bemben, L. A., Berka, J., Braverman, M. S., Chen, Y.-J., Chen, Z., (2005) Genome sequencing in microfabricated high-density picolitre reactors. Nature, 437, 376–380

[8] Bowers, J., Mitchell, J., Beer, E., Buzby, P. R., Causey, M., Efcavitch, J. W., Jarosz, M., Krzymanska-Olejnik, E., Kung, L., Lipson, D., (2009) Virtual terminator nucleotides for next-generation DNA sequencing. Nat. Methods, 6, 593–595

[9] Eid, J., Fehr, A., Gray, J., Luong, K., Lyle, J., Otto, G., Peluso, P., Rank, D., Baybayan, P., Bettman, B., (2009) Real-time DNA sequencing from single polymerase molecules. Science, 323, 133–138

[10] Goldfeder, R. L., Priest, J. R., Zook, J. M., Grove, M. E., Waggott, D., Wheeler, M. T., Salit, M. and Ashley, E. A. (2016) Medical implications of technical accuracy in genome sequencing. Genome Med., 8, 24

[11] Kasianowicz, J. J., Brandin, E., Branton, D. and Deamer, D. W. (1996) Characterization of individual polynucleotide molecules using a membrane channel. Proc. Natl. Acad. Sci. USA, 93, 13770–13773

[12] Branton, D., Deamer, D. W., Marziali, A., Bayley, H., Benner, S. A., Butler, T., Di Ventra, M., Garaj, S., Hibbs, A., Huang, X., (2008) The potential and challenges of nanopore sequencing. Nat. Biotechnol., 26, 1146–1153

[13] Lubensky, D. K. and Nelson, D. R. (1999) Driven polymer translocation through a narrow pore. Biophys. J., 77, 1824–1838

[14] Meller, A., Nivon, L., Brandin, E., Golovchenko, J. and Branton, D. (2000) Rapid nanopore discrimination between single polynucleotide molecules. Proc. Natl. Acad. Sci. USA, 97, 1079–1084

[15] Li, J. and Talaga, D. S. (2010) The distribution of DNA translocation times in solid-state nanopores. J. Phys. Condens. Matter, 22, 454129

[16] Ling, X.S., Bready, B.; Pertsinidis, A. (2006) Hybridization assisted nanopore sequencing. WO2007041621A3, International Application No.: PCT/US2006/038748

[17] Southern, E. M. (1975) Detection of specific sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol., 98, 503–517

[18] Drmanac, R., Drmanac, S., Chui, G., Diaz, R., Hou, A., Jin, H., Jin, P., Kwon, S., Lacy, S., Moeur, B., (2002) Sequencing by hybridization (SBH): advantages, achievements, and opportunities. Adv. Biochem. Eng. Biotechnol., 77, 75–101

[19] Balagurusamy, V. S., Weinger, P. and Ling, X. S. (2010) Detection of DNA hybridizations using solid-state nanopores. Nanotechnology, 21, 335102

[20] Ling, X. S. (2013). Methods of sequencing nucleic acids using nanopores and active kinetic proofreading. WO/2013/119784, International Application No.: PCT/US2013/025106

[21] Hopfield, J. J. (1974) Kinetic proofreading: a new mechanism for reducing errors in biosynthetic processes requiring high specificity. Proc. Natl. Acad. Sci. USA, 71, 4135–4139

[22] Ninio, J. (1975) Kinetic amplification of enzyme discrimination. Biochimie, 57, 587–595

[23] Ling, X. S. and Yuan, Z. (2017) A method for fabricating bi-layer nanopore structures for sequencing DNA. China National Bureau on Intellectual Property. Patent number ZL 2016 1 0256247.9

[24] Kim, D.-K., Kwon, Y.-S., Takamura, Y. and Tamiya, E. (2006) Detection of DNA hybridization properties using thermodynamic method. Jpn. J. Appl. Phys., 45, 509–512

[25] Pertsinidis, A. (2018) Private Communications

[26] Gunnarsson, A., Jönsson, P., Zhdanov, V. P. and Höök, F. (2009) Kinetic and thermodynamic characterization of single-mismatch discrimination using single-molecule imaging. Nucleic Acids Res., 37, e99

[27] Hynes, J. T. (1985) The theory of chemical reactions in solutions. In: Theory of Chemical Reaction Dynamics, Baer, M., (ed.), Vol. IV, pp.171235. Boca Raton: CRC

[28] Sorgenfrei, S., Chiu, C. Y., Gonzalez, R. L. Jr, Yu, Y.-J., Kim, P., Nuckolls, C. and Shepard, K. L. (2011) Label-free single-molecule detection of DNA-hybridization kinetics with a carbon nanotube field-effect transistor. Nat. Nanotechnol., 6, 126–132

[29] Schrödinger, E. (1915) Zur Theorie der Fall-und Steigversuche an Teilchen mit Brownscher Bewegung. Phys. Z., 16, 289–295

[30] Ling, D. Y. and Ling, X. S. (2013) On the distribution of DNA translocation times in solid-state nanopores: an analysis using Schrödinger’s first-passage-time theory. J. Phys. Condens. Matter, 25, 375102

[31] Robertson, R. M., Laib, S. and Smith, D. E. (2006) Diffusion of isolated DNA molecules: dependence on length and topology. Proc. Natl. Acad. Sci. USA, 103, 7310–7314

[32] Smith, S. B., Cui, Y. and Bustamante, C. (1996) Overstretching B-DNA: the elastic response of individual double-stranded and single-stranded DNA molecules. Science, 271, 795–799

[33] Peng, H. and Ling, X. S. (2009) Reverse DNA translocation through a solid-state nanopore by magnetic tweezers. Nanotechnology, 20, 185101

AUTHOR CONTRIBUTIONS

The author is the original contributor of the concepts discussed in the article.

FUNDING

The patented device concept [²³] described in this paper was developed while the author was spending a sabbatical year as consulting professor (visitor) at Southeast University, Nanjing, China, during which he received a partial sabbatical salary from Brown University and a stipend (living-expense) from Southeast University.

ACKNOWLEDGMENTS

The author is grateful to Professor Terence Hwa for an early helpful conversation, and to Wang Miao for carrying out the COMSOL calculation in Fig. 2, and to Alexandros Pertsinidis and Zhishan Yuan for useful discussions, and to Professors Yunfei Chen, Zuhong Lu, and Jingjie Sha for assistance, to Southeast University (Nanjing, China) for hospitality and financial support for his sabbatical year (2016-2017) in Nanjing during which the bulk of this work was done.

COMPLIANCE WITH ETHICS GUIDELINES

The author is a co-founder and consultant of the Nanjing Rhode Island Nanotech Ltd. (Nanjing, China) and NJRI Suzhou Ltd. (Suzhou, China) which acquired the patent [²³] discussed in this article.ƒThis article is a review article and does not contain any studies with human or animal subjects performed by the author.

RIGHTS & PERMISSIONS

2020 Higher Education Press and Springer-Verlag GmbH Germany, part of Springer Nature