Ulysse McConnell | Searcharxiv

arXiv2026

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

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

q-bio.GN↗

arXiv2025

RawBench: A Comprehensive Benchmarking Framework for Raw Nanopore Signal Analysis Techniques

Nanopore sequencing technologies continue to advance rapidly, offering critical benefits such as real-time analysis, the ability to sequence extremely long DNA fragments (up to millions of bases in a single read), and the option to selectively stop sequencing a molecule before completion. Traditionally, the raw electrical signals generated during sequencing are converted into DNA sequences through a process called basecalling, which typically relies on large neural network models. Raw signal analysis has emerged as a promising alternative to these resource-intensive approaches. While attempts have been made to benchmark conventional basecalling methods, existing evaluation frameworks 1) overlook raw signal analysis techniques, 2) lack the flexibility to accommodate new raw signal analysis tools easily, and 3) fail to include the latest improvements in nanopore datasets. Our goal is to provide an extensible benchmarking framework that enables designing and comparing new methods for raw signal analysis. To this end, we introduce RawBench, the first flexible framework for evaluating raw nanopore signal analysis techniques. RawBench provides modular evaluation of three core pipeline components: 1) reference genome encoding (using different pore models), 2) signal encoding (through various segmentation methods), and 3) representation matching (via different data structures). We extensively evaluate raw signal analysis techniques in terms of 1) quality and performance for read mapping, 2) quality and performance for read classification, and 3) quality of raw signal analysis-assisted basecalling. Our evaluations show that raw signal analysis can achieve competitive quality while significantly reducing resource requirements, particularly in settings where real-time processing or edge deployment is necessary.

q-bio.GN↗