@article{Liu01112024,
author = {Liu, Xudong and Ni, Ying and Ye, Lianwei and Guo, Zhihao and Tan, Lu and Li, Jun and Yang, Mengsu and Chen, Sheng and Li, Runsheng}, 
title = {Nanopore strand-specific mismatch enables de novo detection of bacterial DNA modifications},
volume = {34}, 
number = {11}, 
pages = {2025-2038}, 
year = {2024}, 
doi = {10.1101/gr.279012.124}, 
abstract ={DNA modifications in bacteria present diverse types and distributions, playing crucial functional roles. Current methods for detecting bacterial DNA modifications via nanopore sequencing typically involve comparing raw current signals to a methylation-free control. In this study, we found that bacterial DNA modification induces errors in nanopore reads. And these errors are found only in one strand but not the other, showing a strand-specific bias. Leveraging this discovery, we developed Hammerhead, a pioneering pipeline designed for de novo methylation discovery that circumvents the necessity of raw signal inference and a methylation-free control. The majority (14 out of 16) of the identified motifs can be validated by raw signal comparison methods or by identifying corresponding methyltransferases in bacteria. Additionally, we included a novel polishing strategy employing duplex reads to correct modification-induced errors in bacterial genome assemblies, achieving a reduction of over 85% in such errors. In summary, Hammerhead enables users to effectively locate bacterial DNA methylation sites from nanopore FASTQ/FASTA reads, thus holds promise as a routine pipeline for a wide range of nanopore sequencing applications, such as genome assembly, metagenomic binning, decontaminating eukaryotic genome assemblies, and functional analysis for DNA modifications.}, 
URL = {http://genome.cshlp.org/content/34/11/2025.abstract}, 
eprint = {http://genome.cshlp.org/content/34/11/2025.full.pdf+html}, 
journal = {Genome Research} 
}