用隐马尔可夫模型修正纳米孔测序原始信号中的错误,提升分析准确率。
CRANE: Correcting Errors in Raw Nanopore Signals Using Hidden Markov Models
- 基于隐马尔可夫模型训练信号纠错机制
- 在多个数据集上显著提升原始信号分析准确率
- 无需额外优化即可适配新测序技术,计算开销小
纳米孔测序可读取比其他方法更长的核酸分子序列(称为reads),推动了无间隙人类基因组组装等进展。通过分析纳米孔测序生成的原始电信号,现有方法可在不进行碱基识别(basecalling)的情况下直接映射序列,实现快速高效的数据分析。然而,原始信号常因噪声和处理误差引入错误,限制了信号分析的整体准确性。本文提出CRANE,一种利用隐马尔可夫模型(HMM)训练并纠正信号错误的机制,以提升原始信号分析精度。大量实验表明,CRANE能:1)持续提升底层原始信号分析工具的整体准确率;2)降低为新型纳米孔技术优化分析流程的负担;3)不引入显著计算开销。结论是,CRANE提供了一种系统性识别与纠正原始纳米孔信号错误的有效方法,可推动专为原始信号设计的新一代纠错机制的发展。源码已公开于https://github.com/STORMgroup/CRANE,附带完整复现脚本。
原文摘要 · Abstract (English)
Nanopore sequencing can read substantially longer sequences of nucleic acid molecules, called reads, than other sequencing methods, which has led to advances in genomic analysis such as the gapless human genome assembly. By analyzing the raw electrical signal reads that nanopore sequencing generates from molecules, existing works can map these reads without translating them into DNA characters (i.e., basecalling), allowing for quick and efficient analysis of sequencing data. However, raw signals often contain errors due to noise and processing errors, which limits the overall accuracy of raw signal analysis. Our goal in this work is to detect and correct errors in raw signals to improve the accuracy of raw signal analyses. To this end, we propose CRANE, a mechanism that trains and utilizes a Hidden Markov Model (HMM) to accurately correct signal errors. Our extensive evaluation on various datasets shows that CRANE 1) consistently improves the overall accuracy of the underlying raw signal analysis tools, 2) minimizes the burden of optimizing analysis pipelines for newer nanopore technologies, and 3) does not introduce substantial computational overhead. We conclude that CRANE provides an effective mechanism to systematically identify and correct the errors in raw nanopore signals before further analysis, which can enable the development of a new class of error correction mechanisms purely designed for raw nanopore signals. Source Code: CRANE is available at https://github.com/STORMgroup/CRANE. We also provide the scripts to fully reproduce our results on our GitHub page
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