TY  - JOUR
A1  - Liu, Xudong
A1  - Ni, Ying
A1  - Ye, Lianwei
A1  - Guo, Zhihao
A1  - Tan, Lu
A1  - Li, Jun
A1  - Yang, Mengsu
A1  - Chen, Sheng
A1  - Li, Runsheng
T1  - Nanopore strand-specific mismatch enables de novo detection of bacterial DNA modifications
Y1  - 2024/11/01 
JF  - Genome Research 
JO  - Genome Research 
SP  - 2025 
EP  - 2038 
DO  - 10.1101/gr.279012.124 
VL  - 34 
IS  - 11 
UR  - http://genome.cshlp.org/content/34/11/2025.abstract 
N2  - 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. 
ER  -