Yuen, Zaka Wing-SzeSrivastava, AkankshaDaniel, RunaMcNevin, DennisJack, CameronEyras Jiménez, Eduardo2022-06-272022-06-272021Yuen ZW, Srivastava A, Daniel R, McNevin D, Jack C, Eyras E. Systematic benchmarking of tools for CpG methylation detection from nanopore sequencing. Nat Commun. 2021 Jun 8;12(1):3438. DOI: 10.1038/s41467-021-23778-62041-1723http://hdl.handle.net/10230/53585DNA methylation plays a fundamental role in the control of gene expression and genome integrity. Although there are multiple tools that enable its detection from Nanopore sequencing, their accuracy remains largely unknown. Here, we present a systematic benchmarking of tools for the detection of CpG methylation from Nanopore sequencing using individual reads, control mixtures of methylated and unmethylated reads, and bisulfite sequencing. We found that tools have a tradeoff between false positives and false negatives and present a high dispersion with respect to the expected methylation frequency values. We described various strategies to improve the accuracy of these tools, including a consensus approach, METEORE ( https://github.com/comprna/METEORE ), based on the combination of the predictions from two or more tools that shows improved accuracy over individual tools. Snakemake pipelines are also provided for reproducibility and to enable the systematic application of our analyses to other datasets.application/pdfeng© The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.Systematic benchmarking of tools for CpG methylation detection from nanopore sequencinginfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1038/s41467-021-23778-6DNA sequencingEpigenomicsGenome informaticsSoftwareinfo:eu-repo/semantics/openAccess