Fast and automatic processing of multi-level events in nanopore translocation experiments.

We have developed a method to analyze in detail, translocation events providing a novel and flexible tool for data analysis of nanopore experiments. Our program, called OpenNanopore, is based on the cumulative sums algorithm (CUSUM algorithm). This algorithm is an abrupt change detection algorithm that provides fitting of current blockages, allowing the user to easily identify the different levels in each event. Our method detects events using adaptive thresholds that adapt to low-frequency variations in the baseline. After event identification, our method uses the CUSUM algorithm to fit the levels inside every event and automatically extracts their time and amplitude information. This facilitates the statistical analysis of an event population with a given number of levels. The obtained information improves the interpretation of interactions between the molecule and nanopore. Since our program does not require any prior information about the analyzed molecules, novel molecule-nanopore interactions can be characterized. In addition our program is very fast and stable. With the progress in fabrication and control of the translocation speed, in the near future, our program could be useful in identification of the different bases of DNA.

[1]  C. Dekker,et al.  Translocation of RecA-coated double-stranded DNA through solid-state nanopores. , 2009, Nano letters.

[2]  M. Drndić,et al.  Nanopore analysis of individual RNA/antibiotic complexes. , 2011, ACS nano.

[3]  N H Dekker,et al.  Noise in solid-state nanopores , 2008, Proceedings of the National Academy of Sciences.

[4]  C. Dekker,et al.  Fabrication of solid-state nanopores with single-nanometre precision , 2003, Nature materials.

[5]  D. McNabb,et al.  Slowing DNA translocation in a solid-state nanopore. , 2005, Nano letters.

[6]  Aleksei Aksimentiev,et al.  Slowing the translocation of double-stranded DNA using a nanopore smaller than the double helix , 2010, Nanotechnology.

[7]  M. Niederweis,et al.  Nanopore DNA sequencing with MspA , 2010, Proceedings of the National Academy of Sciences.

[8]  Fernando Albertorio,et al.  Origins and consequences of velocity fluctuations during DNA passage through a nanopore. , 2011, Biophysical journal.

[9]  D. Talaga,et al.  Single-molecule protein unfolding in solid state nanopores. , 2009, Journal of the American Chemical Society.

[10]  Elisabeth J. Umble,et al.  Cumulative Sum Charts and Charting for Quality Improvement , 2001, Technometrics.

[11]  G. Moustakides.  Optimal stopping times for detecting changes in distributions , 1986 .

[12]  Douglas C. Montgomery,et al.  Statistical quality control : a modern introduction , 2009 .

[13]  Michèle Basseville,et al.  Detection of abrupt changes: theory and application , 1993 .

[14]  David Haussler,et al.  Highly accurate classification of Watson-Crick basepairs on termini of single DNA molecules. , 2003, Biophysical journal.

[15]  Cees Dekker,et al.  Modeling the conductance and DNA blockade of solid-state nanopores , 2011, Nanotechnology.

[16]  J. Gilman,et al.  Nanotechnology , 2001 .

[17]  A. Radenović,et al.  Nanopore detection of single molecule RNAP-DNA transcription complex. , 2012, Nano letters.

[18]  Jeremy S. Lee,et al.  Evidence that small proteins translocate through silicon nitride pores in a folded conformation , 2010, Journal of physics. Condensed matter : an Institute of Physics journal.

[19]  Cees Dekker,et al.  Distinguishing single- and double-stranded nucleic acid molecules using solid-state nanopores. , 2009, Nano letters.

[20]  K. Pearson,et al.  Biometrika , 1902, The American Naturalist.

[21]  Shoji Takeuchi,et al.  A rupture detection algorithm for the DNA translocation detection though biological nanopore , 2010 .

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

[23]  O. Otto,et al.  Probing DNA with micro- and nanocapillaries and optical tweezers , 2010, Journal of physics. Condensed matter : an Institute of Physics journal.

[24]  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.

[25]  R. Rosenfeld.  Nature , 2009, Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery.

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

[27]  Z. Siwy,et al.  Origin of 1/f(alpha) noise in membrane channel currents. , 2002, Physical review letters.

[28]  F Sachs,et al.  A direct optimization approach to hidden Markov modeling for single channel kinetics. , 2000, Biophysical journal.

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

[30]  Y. Ritov.  Decision Theoretic Optimality of the Cusum Procedure , 1990 .

[31]  Meni Wanunu,et al.  DNA translocation governed by interactions with solid-state nanopores. , 2008, Biophysical journal.

[32]  N. Dekker,et al.  Distinguishable populations report on the interactions of single DNA molecules with solid-state nanopores. , 2010, Biophysical journal.

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

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

[35]  C. Dekker,et al.  Translocation of double-strand DNA through a silicon oxide nanopore. , 2005, Physical review. E, Statistical, nonlinear, and soft matter physics.

[36]  Feng Qin,et al.  Model-based fitting of single-channel dwell-time distributions. , 2004, Biophysical journal.

[37]  J. Gouaux,et al.  Structure of Staphylococcal α-Hemolysin, a Heptameric Transmembrane Pore , 1996, Science.

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

[39]  E. S. Page.  CONTINUOUS INSPECTION SCHEMES , 1954 .

[40]  Marc Gershow,et al.  DNA molecules and configurations in a solid-state nanopore microscope , 2003, Nature materials.

[41]  D. Talaga,et al.  The distribution of DNA translocation times in solid-state nanopores , 2010, Journal of physics. Condensed matter : an Institute of Physics journal.

[42]  宁北芳,et al.  疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A , 2005 .

[43]  G. Lorden.  PROCEDURES FOR REACTING TO A CHANGE IN DISTRIBUTION , 1971 .

[44]  S. Garaj,et al.  Probing surface charge fluctuations with solid-state nanopores. , 2009, Physical review letters.

[45]  Peng Chen,et al.  Atomic Layer Deposition to Fine-Tune the Surface Properties and Diameters of Fabricated Nanopores. , 2004, Nano letters.

[46]  U. Keyser,et al.  Nanobubbles in solid-state nanopores. , 2006, Physical review letters.

[47]  Alexander G. Churbanov,et al.  Clustering ionic flow blockade toggles with a Mixture of HMMs , 2008, BMC Bioinformatics.

[48]  Harrison M. Wadsworth,et al.  Modern methods for quality control and improvement , 1986 .

[49]  U. Rant,et al.  Data analysis of translocation events in nanopore experiments. , 2009, Analytical chemistry.

[50]  Andre Marziali,et al.  Noise analysis and reduction in solid-state nanopores , 2007 .

[51]  D. Branton,et al.  Rapid nanopore discrimination between single polynucleotide molecules. , 2000, Proceedings of the National Academy of Sciences of the United States of America.