CERN: Correcting Errors in Raw Nanopore Signals Using Hidden Markov Models

Nanopore sequencing can read substantially longer sequences of nucleic acid molecules 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 mistakes when processing them, 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 CERN, a mechanism that trains and utilizes a Hidden Markov Model (HMM) to accurately correct signal errors. Our extensive evaluation on various datasets including E. coli, Fruit Fly, and Human genomes shows that CERN 1) consistently improves the overall mapping accuracy of the underlying raw signal analysis tools, 2) minimizes the burden on segmentation algorithm optimization with newer nanopore chemistries, and 3) functions without causing substantial computational overhead. We conclude that CERN 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. CERN is available at https://github.com/STORMgroup/CERN. We also provide the scripts to fully reproduce our results on our GitHub page.