基于纳米孔DNA测序的噪声分析

Noise Analysis based on Nanopore DNA Sequencing

基于纳米孔的DNA测序技术以其快捷、低成本和能够检测长片段DNA等优势而备受瞩目。目前,纳米孔DNA测序中,核苷酸通过纳米孔所形成的原始基准离子电流是非常小的,为皮安(pA)级。如果考虑信号放大,放大电路会同时放大噪音信号和调制信号,信噪比并不能有效地提高。因此,对过孔原始电流进行去噪声处理能够有效提高DNA序列的测序精度。本文首先研究探讨了现阶段两种不同纳米孔测序的原理,包括基于库尔特计数器原理的纳米孔测序与基于隧道电流检测法的纳米孔测序。然后,对在纳米孔测序过程中起主要影响1/?噪声、Johnson热噪声以及气泡噪声的作用机理进行了分析。最后,通过选取不同的小波基函数和小波分解层数,利用小波滤波方法提升了测序电流信号的信噪比,有效地去除了信号中的噪声。

DNA sequencing technology based on nanopore has attracted more and more attention because of its advantages such as fast,low cost and the ability to detect long DNA fragments.At present,in nanopore DNA sequencing,the original reference ion current formed by nucleotides passing through the nanopore is very small,which is pA level.If the signal amplification is considered,the amplifying circuit will amplify the noise signal and the modulation signal at the same time,and the SNR cannot be effectively improved.Therefore,the denoising of the via current can effectively improve the sequencing accuracy of DNA sequence.In this paper,we first discuss the principles of two different nanopore sequencing,including the Kurt counter based nanopore sequencing and the tunneling current detection based nanopore sequencing.Then,the mechanisms of 1/?noise,Johnson thermal noise and bubble noise in the process of re nanopore sequencing were analyzed.Finally,by selecting different wavelet basis functions and wavelet decomposition layers,it is found that the method of wavelet filtering can improve the signal-to-noise ratio of sequencing current signal and effectively remove the noise in the signal.