Models and Information-Theoretic Bounds for Nanopore Sequencing
Models and Information-Theoretic Bounds for Nanopore Sequencing
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DOI：
10.1109/tit.2018.2809001
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发表时间：
2018-04-01
影响因子：
2.5
通讯作者：
Kannan, Sreeram
中科院分区：
文献类型：
--
作者：
Mao, Wei;Diggavi, Suhas N.;Kannan, Sreeram
纳米孔测序是一种新兴的脱氧核糖核酸(DNA)测序新技术，它可以读取DNA的长片段(类似于5万个碱基)，而不是目前大多数短读测序技术只能读取数百个碱基。虽然纳米孔测序仪可以获得长时间的读数，但高错误率(20%-30%)构成了技术挑战。在纳米孔测序仪中，DNA通过纳米孔迁移，并测量电流变化。DNA序列是使用一种称为碱基呼叫者的算法从观察到的电流模式中推断出来的。在本文中，我们提出了从输入DNA序列到观测电流的“通道”的数学模型，并计算了纳米孔测序仪信息提取能力的界限。该模型包含损伤，例如(非线性)符号间干扰、删除和随机响应。这些信息界有两个方面的应用：1)在给定观察到的电流轨迹的情况下，均匀输入分布的译码率可以用来计算DNA序列的合理列表的平均大小。这一界限可以用来对现有的基本调用算法进行基准测试，也可以服务于设计更好的纳米孔的性能目标。2)当纳米孔测序仪用作DNA存储系统中的读取器时，存储容量是由我们的界限来量化的。
Nanopore sequencing is an emerging new technology for sequencing Deoxyribonucleic acid (DNA), which can read long fragments of DNA (similar to 50 000 bases), in contrast to most current short-read sequencing technologies which can only read hundreds of bases. While nanopore sequencers can acquire long reads, the high error rates (20%-30%) pose a technical challenge. In a nanopore sequencer, a DNA is migrated through a nanopore, and current variations are measured. The DNA sequence is inferred from this observed current pattern using an algorithm called a base-caller. In this paper, we propose a mathematical model for the "channel" from the input DNA sequence to the observed current, and calculate bounds on the information extraction capacity of the nanopore sequencer. This model incorporates impairments, such as (non-linear) inter-symbol interference, deletions, and random response. These information bounds have two-fold application: 1) The decoding rate with a uniform input distribution can be used to calculate the average size of the plausible list of DNA sequences given an observed current trace. This bound can be used to benchmark existing base-calling algorithms, as well as serving a performance objective to design better nanopores. 2) When the nanopore sequencer is used as a reader in a DNA storage system, the storage capacity is quantified by our bounds.