Fast and sensitive mapping of bisulfite-treated sequencing data

Bioinformatics
Christian OttoSteve Hoffmann

Abstract

Cytosine DNA methylation is one of the major epigenetic modifications and influences gene expression, developmental processes, X-chromosome inactivation, and genomic imprinting. Aberrant methylation is furthermore known to be associated with several diseases including cancer. The gold standard to determine DNA methylation on genome-wide scales is 'bisulfite sequencing': DNA fragments are treated with sodium bisulfite resulting in the conversion of unmethylated cytosines into uracils, whereas methylated cytosines remain unchanged. The resulting sequencing reads thus exhibit asymmetric bisulfite-related mismatches and suffer from an effective reduction of the alphabet size in the unmethylated regions, rendering the mapping of bisulfite sequencing reads computationally much more demanding. As a consequence, currently available read mapping software often fails to achieve high sensitivity and in many cases requires unrealistic computational resources to cope with large real-life datasets. In this study, we present a seed-based approach based on enhanced suffix arrays in conjunction with Myers bit-vector algorithm to efficiently extend seeds to optimal semi-global alignments while allowing for bisulfite-related substitutions. It out...Continue Reading

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Sep 19, 2012·Nature Reviews. Genetics·Christoph Bock
May 21, 2014·PloS One·Andrea ManconiLuciano Milanesi
Mar 15, 2014·Bioinformatics·Christian OttoSteve Hoffmann
Jan 7, 2014·Nucleic Acids Research·Govindarajan Kunde-RamamoorthyRobert A Waterland
Oct 15, 2014·Proceedings of the National Academy of Sciences of the United States of America·Dan Levy, Michael Wigler
May 28, 2013·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Pingchuan LiBlake C Meyers
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Nov 23, 2017·Frontiers in Physiology·Clemens KreutzMaría M Bartolomé-Rodríguez
Apr 8, 2020·Frontiers in Plant Science·Claudius GrehlIvo Grosse
Oct 28, 2017·Scientific Reports·Matus ValachGertraud Burger
Jul 10, 2021·Nature Microbiology·Falk PonathJörg Vogel

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