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

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.

[1]  Yue Wang,et al.  The evolution of nanopore sequencing , 2014, Front. Genet..

[2]  Yuri S. Kivshar,et al.  Fano Resonances in Nanoscale Structures , 2010 .

[3]  Jacob J. Schmidt,et al.  Nucleotide identification and orientation discrimination of DNA homopolymers immobilized in a protein nanopore. , 2008, Nano letters.

[4]  Carlo Cavazzoni,et al.  Electronic structure of single DNA molecules resolved by transverse scanning tunnelling spectroscopy. , 2008, Nature materials.

[5]  M. Di Ventra,et al.  Influence of the environment and probes on rapid DNA sequencing via transverse electronic transport. , 2007, Biophysical journal.

[6]  Charge transfer in DNA: effective Hamiltonian approaches , 2009 .

[7]  M. Taniguchi,et al.  Single-molecule sensing electrode embedded in-plane nanopore , 2011, Scientific reports.

[8]  Y. Pershin,et al.  DNA characterization by transverse electrical current in a nanochannel. , 2012, Methods in molecular biology.

[9]  D. Branton,et al.  The potential and challenges of nanopore sequencing , 2008, Nature Biotechnology.

[10]  M. Ventra,et al.  Colloquium: Physical approaches to DNA sequencing and detection , 2007, 0708.2724.

[11]  Aleksei Aksimentiev,et al.  DNA base-calling from a nanopore using a Viterbi algorithm. , 2012, Biophysical journal.

[12]  M. Ventra Fast DNA sequencing by electrical means inches closer. , 2013 .

[13]  L. Serrano-Andrés,et al.  Ab initio determination of the electron affinities of DNA and RNA nucleobases. , 2008, The Journal of chemical physics.

[14]  Hanlee P. Ji,et al.  Next-generation DNA sequencing , 2008, Nature Biotechnology.

[15]  Meir,et al.  Landauer formula for the current through an interacting electron region. , 1992, Physical review letters.

[16]  Daniel Roca-Sanjuán,et al.  Ab initio determination of the ionization potentials of DNA and RNA nucleobases. , 2006, The Journal of chemical physics.

[17]  Makusu Tsutsui,et al.  Single-Molecule Electrical Random Resequencing of DNA and RNA , 2012, Scientific Reports.

[18]  J. Freire,et al.  Effective Hamiltonians for the nonorthogonal basis set , 2003 .

[19]  A. Kasarskis,et al.  A window into third-generation sequencing. , 2010, Human molecular genetics.

[20]  Nicola Marzari,et al.  Surface energies, work functions, and surface relaxations of low index metallic surfaces from first principles , 2008, 0801.1077.

[21]  Marc Gershow,et al.  Recapturing and trapping single molecules with a solid-state nanopore. , 2007, Nature nanotechnology.

[22]  H. Bayley,et al.  Individual RNA base recognition in immobilized oligonucleotides using a protein nanopore. , 2012, Nano letters.

[23]  S. Roche Sequence dependent DNA-mediated conduction. , 2003, Physical review letters.

[24]  Michael Zwolak,et al.  Electronic signature of DNA nucleotides via transverse transport. , 2004, Nano letters.

[25]  F. Sanger,et al.  The amino-acid sequence in the phenylalanyl chain of insulin. I. The identification of lower peptides from partial hydrolysates. , 1951, The Biochemical journal.

[26]  S. Turner,et al.  Going beyond five bases in DNA sequencing. , 2012, Current opinion in structural biology.

[27]  L. Hood,et al.  Complete genomic sequence and analysis of 117 kb of human DNA containing the gene BRCA1. , 1996, Genome research.

[28]  Y. Ishikawa,et al.  A combined DFT/Green's function study on electrical conductivity through DNA duplex between Au electrodes. , 2009, Chemical physics letters.

[29]  D. Branton,et al.  Characterization of individual polynucleotide molecules using a membrane channel. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[30]  F. Sanger,et al.  DNA sequencing with chain-terminating inhibitors. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[31]  H. Bayley,et al.  Translocating kilobase RNA through the Staphylococcal α-hemolysin nanopore. , 2013, Nano letters.

[32]  J. Freire,et al.  Electron transfer in proteins: nonorthogonal projections onto donor-acceptor subspace of the Hilbert space. , 2004, The Journal of chemical physics.

[33]  T. Chakraborty,et al.  Physics Aspects of Charge Migration Through DNA , 2007 .

[34]  Y. Ishikawa,et al.  A combined nonequilibrium Green’s function/density-functional theory study of electrical conducting properties of artificial DNA duplexes , 2012 .

[35]  J. Winkler,et al.  Electron Transfer In Proteins , 1997, QELS '97., Summaries of Papers Presented at the Quantum Electronics and Laser Science Conference.

[36]  D. Branton,et al.  Microsecond time-scale discrimination among polycytidylic acid, polyadenylic acid, and polyuridylic acid as homopolymers or as segments within single RNA molecules. , 1999, Biophysical journal.

[37]  Y. Pershin,et al.  Effect of noise on DNA sequencing via transverse electronic transport. , 2009, Biophysical journal.

[38]  J. Joanny,et al.  Fast DNA translocation through a solid-state nanopore. , 2004, Nano letters.

[39]  Electrical transport through single-molecule junctions: from molecular orbitals to conduction channels. , 2001, Physical review letters.

[40]  M. Taniguchi,et al.  Identifying single nucleotides by tunnelling current. , 2010, Nature nanotechnology.

[41]  A. Meller,et al.  DNA profiling using solid-state nanopores: detection of DNA-binding molecules. , 2009, Nano letters.

[42]  M. Metzker Sequencing technologies — the next generation , 2010, Nature Reviews Genetics.

[43]  Marc Gershow,et al.  Detecting single stranded DNA with a solid state nanopore. , 2005, Nano letters.

[44]  K. Kitaura,et al.  Fragment molecular orbital method: an approximate computational method for large molecules , 1999 .

[45]  S Mohammadi,et al.  A nanofluidic channel with embedded transverse nanoelectrodes , 2009, Nanotechnology.

[46]  Michael Zwolak,et al.  Fast DNA sequencing via transverse electronic transport. , 2006, Nano letters.

[47]  Laurence G. D. Hawke,et al.  Electronic parameters for charge transfer along DNA , 2009, The European physical journal. E, Soft matter.

[48]  J. G. Snijders,et al.  Towards an order-N DFT method , 1998 .

[49]  D. Beratan,et al.  Ab initio based effective Hamiltonians for long‐range electron transfer: Hartree–Fock analysis , 1996 .

[50]  C. Dekker Solid-state nanopores. , 2007, Nature nanotechnology.

[51]  H. Bayley,et al.  Sequencing single molecules of DNA. , 2006, Current opinion in chemical biology.

[52]  Soohyung Park,et al.  Energy level alignment at the interfaces between typical electrodes and nucleobases: Al/adenine/indium-tin-oxide and Al/thymine/indium-tin-oxide , 2012 .

[53]  S. Massey,et al.  Intrinsic Noise from Neighboring Bases in the DNA Transverse Tunneling Current , 2014 .

[54]  Michael J. Aziz,et al.  Ion-beam sculpting at nanometre length scales , 2001, Nature.

[55]  Meni Wanunu,et al.  Nanopore based sequence specific detection of duplex DNA for genomic profiling. , 2010, Nano letters.

[56]  M. A. Soto,et al.  Fast DNA sequencing. , 2000, Medical hypotheses.

[57]  David Stoddart,et al.  Single-nucleotide discrimination in immobilized DNA oligonucleotides with a biological nanopore , 2009, Proceedings of the National Academy of Sciences.

[58]  Hutchinson Ge THE INFLUENCE OF THE ENVIRONMENT , 1964 .

[59]  S. Roche,et al.  Point-mutation effects on charge-transport properties of the tumor-suppressor gene p53. , 2007, Physical review letters.

[60]  J. Palacios,et al.  Theory of projections with nonorthogonal basis sets: Partitioning techniques and effective Hamiltonians , 2014, 1404.2043.

[61]  Jin He,et al.  Electronic Signatures of all Four DNA Nucleosides in a Tunneling Gap , 2010, Nano letters.

[62]  F. Matthias Bickelhaupt,et al.  Chemistry with ADF , 2001, J. Comput. Chem..

[63]  S. Lindsay,et al.  Transverse tunneling through DNA hydrogen bonded to an electrode. , 2008, Nano letters.

[64]  H. Bayley,et al.  Continuous base identification for single-molecule nanopore DNA sequencing. , 2009, Nature nanotechnology.

[65]  Semiconductivity and Band Gap of a Double Strand of DNA , 2001 .

[66]  David W. McComb,et al.  DNA Tunneling Detector Embedded in a Nanopore , 2010, Nano letters.

[67]  H. Bayley,et al.  Nanopore-based identification of individual nucleotides for direct RNA sequencing. , 2013, Nano letters.