DNMTools

A set of tools for analyzing DNA methylation data from high-throughput sequencing experiments, especially whole genome bisulfite sequencing (WGBS), but also reduced representation bisulfite sequencing (RRBS). These tools focus on overcoming the computing challenges imposed by the scale of genome-wide DNA methylation data, which is usually the early parts of data analysis.

DNMTools supersedes our MethPipe software, but includes all the same functionality (or soon will). The design of DNMTools differs, but most commands within DNMTools are in one-to-one correspondence with some tool in MethPipe.

At present, as we make the first release of DNMTools, the documentation is structured very differently from that of MethPipe. We are rebuilding that documentation here, but it might take a few iterations to stabilize. Most of the old documentation still applies for tasks that do not directly involve our tools (e.g., how to manipulate the files with basic terminal commands). If you are already a user of our tools, please check the documentation here in case individual commands within DNMTools have changes to command line arguments or file formats.

Assumptions

Our tools were designed to run in a cluster computing context, with many processing nodes available, and a job submission system like PBS/SGE or SLURM. But now it is also possible to analyze methylomes from most genomes (including human and mouse) in a local machine with 16 GB of RAM. Given that abismal is so fast and memory efficient, even less may be required. Typically the data we deal with amounts to a minimum of 100GB for a mammalian methylome at 10x coverage. This data expands during processing before the final files are ready. Intermediate files may cause this amount to more than double during execution of any of our pipelines.

It is critical that users are familiar with bisulfite sequencing experiments, especially the bisulfite conversion reaction, and how this affects what we observe in the sequenced reads.

Users are assumed to be somewhat familar with a command line. Installing DNMTools might require working with some environment variables. The data that DNMTools is designed for is really big, so understanding your computer is important. We also assume users know what standard output and standard error are.

Citation information

If you find our tools helpful, please cite us. Many of the commands within DNMTools were introduced in their own publications. However, several improvements and additions have been made over the years. Below are the relevant citations.

DNMTools

Qiang Song, Benjamin Decato, Elizabeth E Hong, Meng Zhou, Fang Fang, Jianghan Qu, Tyler Garvin, Michael Kessler, Jun Zhou, and Andrew D Smith. A reference methylome database and analysis pipeline to facilitate integrative and comparative epigenomics. PloS ONE, 8(12):e81148, 2013

abismal

Guilherme de Sena Brandine, and Andrew D Smith Fast and memory-efficient mapping of short bisulfite sequencing reads using a two-letter alphabet. NAR Genomics and Bioinformatics, 3(4), lqab115, 2021.

amrfinder

Fang Fang, Emily Hodges, Antoine Molaro, Matthew Dean, Gregory J Hannon, and Andrew D Smith. Genomic landscape of human allele-specific dna methylation. Proceedings of the National Academy of Sciences, 109(19):7332–7337, 2012

mlml

Jianghan Qu, Meng Zhou, Qiang Song, Elizabeth E Hong, and Andrew D Smith. Mlml: Consistent simultaneous estimates of dna methylation and hydroxymethylation. Bioinformatics, 29(20):2645–2646, 2013

radmeth

Egor Dolzhenko and Andrew D Smith. Using beta-binomiaregression for high-precision differen tial methylation analysis in multifactor whole-genome bisulfite sequencing experiments. BMC bioinformatics, 15(1):1–8, 2014

pmd

Benjamin E Decato, Jianghan Qu, Xiaojing Ji, Elvin Wagenblast, Simon RV Knott, Gregory J Hannon, and Andrew D Smith. Characterization of universal features of partially methylated domains across tissues and species. Epigenetics & Chromatin, 2020

Contacts and bug reports

Andrew D. Smith andrewds@usc.edu

Guilherme de Sena Brandine desenabr@usc.edu

Copyright and License Information

Copyright (C) 2023 Andrew D. Smith and Guilherme de Sena Brandine

Authors of DNMTools: Andrew D. Smith and Guilherme de Sena Brandine

Essential contributors: Ben Decato, Meng Zhou, Liz Ji, Terence Li, Jenny Qu, Qiang Song and Fang Fang

This is free software: you can redistribute it and/or modify it under the terms of the GNU General Public License as published by the Free Software Foundation, either version 3 of the License, or (at your option) any later version.

This software is distributed in the hope that it will be useful, but WITHOUT ANY WARRANTY; without even the implied warranty of MERCHANTABILITY or FITNESS FOR A PARTICULAR PURPOSE. See the GNU General Public License for more details.