Identifying and correcting repeat-calling errors in nanopore sequencing of telomeres

Genome Biol. 2022 Aug 26;23(1):180. doi: 10.1186/s13059-022-02751-6.

Abstract

Nanopore long-read sequencing is an emerging approach for studying genomes, including long repetitive elements like telomeres. Here, we report extensive basecalling induced errors at telomere repeats across nanopore datasets, sequencing platforms, basecallers, and basecalling models. We find that telomeres in many organisms are frequently miscalled. We demonstrate that tuning of nanopore basecalling models leads to improved recovery and analysis of telomeric regions, with minimal negative impact on other genomic regions. We highlight the importance of verifying nanopore basecalls in long, repetitive, and poorly defined regions, and showcase how artefacts can be resolved by improvements in nanopore basecalling models.

Keywords: Basecalling; Long-reads; Nanopore-sequencing; Telomere.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Genomics
  • High-Throughput Nucleotide Sequencing
  • Nanopore Sequencing*
  • Nanopores*
  • Repetitive Sequences, Nucleic Acid
  • Sequence Analysis, DNA
  • Telomere