Sigmoni: classification of nanopore signal with a compressed pangenome index

Abstract

Improvements in nanopore sequencing necessitate efficient classification methods, including pre-filtering and adaptive sampling algorithms that enrich for reads of interest. Signal-based approaches circumvent the computational bottleneck of basecalling. But past methods for signal-based classification do not scale efficiently to large, repetitive references like pangenomes, limiting their utility to partial references or in- dividual genomes. We introduce Sigmoni: a rapid, multiclass classification method based on the r-index that scales to references of hundreds of Gbps. Sigmoni quantizes nanopore signal into a discrete alphabet of picoamp ranges. It performs rapid, approximate matching using matching statistics, classifying reads based on distributions of picoamp matching statistics and co-linearity statistics. Sigmoni is 10-100X faster than previous methods for adaptive sampling in host depletion experiments with improved accuracy, and can query reads against large microbial or human pangenomes.

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

“…Signal alignment is useful in other applications, for example in several recent rapid signal mappers designed for targeted sequencing [7,8,40,41]. Uncalled4 could be useful in optimization of such approaches, and the Python module is already used by Sigmoni for basic signal processing [40]. Uncalled4 will also be valuable in understanding future updates to nanopore sequencing chemistry, and will aid other signal-based methods in adapting to those changes.…”

“…We have presented a toolkit for nanopore signal alignment and analysis, focusing on applications in nucleotide modification detection. Signal alignment is useful in other applications, for example in several recent rapid signal mappers designed for targeted sequencing [7,8,40,41]. Uncalled4 could be useful in optimization of such approaches, and the Python module is already used by Sigmoni for basic signal processing [40].…”