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基于有偏随机游走模型的纳米孔测序统计推断

Statistical inference for nanopore sequencing with a biased random walk model.

作者信息

Emmett Kevin J, Rosenstein Jacob K, van de Meent Jan-Willem, Shepard Ken L, Wiggins Chris H

机构信息

Department of Physics, Columbia University, New York, New York.

School of Engineering, Brown University, Providence, Rhode Island.

出版信息

Biophys J. 2015 Apr 21;108(8):1852-5. doi: 10.1016/j.bpj.2015.03.013.

Abstract

Nanopore sequencing promises long read-lengths and single-molecule resolution, but the stochastic motion of the DNA molecule inside the pore is, as of this writing, a barrier to high accuracy reads. We develop a method of statistical inference that explicitly accounts for this error, and demonstrate that high accuracy (>99%) sequence inference is feasible even under highly diffusive motion by using a hidden Markov model to jointly analyze multiple stochastic reads. Using this model, we place bounds on achievable inference accuracy under a range of experimental parameters.

摘要

纳米孔测序有望实现长读长和单分子分辨率,但截至撰写本文时,DNA分子在孔内的随机运动是高精度读取的一个障碍。我们开发了一种统计推断方法,明确考虑了这种误差,并证明即使在高度扩散运动的情况下,通过使用隐马尔可夫模型联合分析多个随机读取,高精度(>99%)的序列推断也是可行的。使用该模型,我们在一系列实验参数下确定了可实现的推断精度的界限。

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本文引用的文献

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Decoding long nanopore sequencing reads of natural DNA.解码天然DNA的长纳米孔测序读数。
Nat Biotechnol. 2014 Aug;32(8):829-33. doi: 10.1038/nbt.2950. Epub 2014 Jun 25.
2
Slow DNA transport through nanopores in hafnium oxide membranes.氧化铪纳米孔内 DNA 的缓慢传输。
ACS Nano. 2013 Nov 26;7(11):10121-10128. doi: 10.1021/nn404326f. Epub 2013 Oct 4.
3
Error analysis of idealized nanopore sequencing.理想化纳米孔测序的误差分析。
Electrophoresis. 2013 Aug;34(15):2137-44. doi: 10.1002/elps.201300174.
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DNA base-calling from a nanopore using a Viterbi algorithm.基于 Viterbi 算法的纳米孔 DNA 碱基读取。
Biophys J. 2012 May 16;102(10):L37-9. doi: 10.1016/j.bpj.2012.04.009. Epub 2012 May 15.
7
Nanopore sensors for nucleic acid analysis.纳米孔传感器用于核酸分析。
Nat Nanotechnol. 2011 Sep 18;6(10):615-24. doi: 10.1038/nnano.2011.129.
10

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