Uncalled4 improves nanopore DNA and RNA modification detection via fast and accurate signal alignment

Kovaka, Sam; Hook, Paul W.; Jenike, Katharine M.; Shivakumar, Vikram S.; Morina, Luke B; Razaghi, Roham; Timp, Winston; Schatz, Michael C.

doi:10.1038/s41592-025-02631-4

articleNature MethodsMar 28, 2025HYBRID OA

Uncalled4 improves nanopore DNA and RNA modification detection via fast and accurate signal alignment

SKSam Kovaka PWPaul W. Hook KMKatharine M. Jenike VSVikram S. Shivakumar LBLuke B Morina

Johns Hopkins University · Johns Hopkins Medicine

PubMed

Indexed incrossrefpubmed

Abstract

Nanopore signal analysis enables detection of nucleotide modifications from native DNA and RNA sequencing, providing both accurate genetic or transcriptomic and epigenetic information without additional library preparation. At present, only a limited set of modifications can be directly basecalled (for example, 5-methylcytosine), while most others require exploratory methods that often begin with alignment of nanopore signal to a nucleotide reference. We present Uncalled4, a toolkit for nanopore signal alignment, analysis and visualization. Uncalled4 features an efficient banded signal alignment algorithm, BAM signal alignment file format, statistics for comparing signal alignment methods and a reproducible de…

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42

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FWCI: 25.02
Percentile: 100%
References: 65

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Topics & keywords

Topics

Keywords

Nanopore
DNA
Nanopore sequencing
SIGNAL (programming language)
Computational biology
RNA
Biophysics
Computer science

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