Abstract

Cytosine DNA methylation is an epigenetic mark implicated in several biological processes. Bisulfite treatment of DNA is acknowledged as the gold standard technique to study methylation. This technique introduces changes in the genomic DNA by converting cytosines to uracils while 5-methylcytosines remain nonreactive. During PCR amplification 5-methylcytosines are amplified as cytosine, whereas uracils and thymines as thymine. To detect the methylation levels, reads treated with the bisulfite must be aligned against a reference genome. Mapping these reads to a reference genome represents a significant computational challenge mainly due to the increased search space and the loss of information introduced by the treatment. To deal with this computational challenge we devised GPU-BSM, a tool based on modern Graphics Processing Units. Graphics Processing Units are hardware accelerators that are increasingly being used successfully to accelerate general-purpose scientific applications. GPU-BSM is a tool able to map bisulfite-treated reads from whole genome bisulfite sequencing and reduced representation bisulfite sequencing, and to estimate methylation levels, with the goal of detecting methylation. Due to the massive parallelization obtained by exploiting graphics cards, GPU-BSM aligns bisulfite-treated reads faster than other cutting-edge solutions, while outperforming most of them in terms of unique mapped reads.

Highlights

  • Regulation of gene expression is a very complex process controlled by multiple factors, including epigenetic ones

  • Graphics Processing Units (GPU)-BSM is a mapping tool able to align single-end and paired-end reads generated from whole-genome bisulfite sequencing (WGBS) and representation bisulfite sequencing (RRBS)

  • Only the second stage of the pipeline has been parallelized on GPU cards

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Summary

Introduction

Regulation of gene expression is a very complex process controlled by multiple factors, including epigenetic ones. Epigenetics studies changes in gene expression that do not involve changes in the underlying DNA sequence [1]. Cytosine DNA methylation is a stable epigenetic mark that plays a very important role in several biological processes, including genomic imprinting, and is often responsible of phenotypic expressions (e.g., cancer) [2]. It involves the addition of a methyl group to the cytosine DNA nucleotides (see Figure 1). Mechanisms of epigenetic regulation include methylation at CpG islands in the promoter region of the gene. Three main approaches (i.e., endonuclease digestion, affinity enrichment and bisulfite conversion) [4] have been developed to analyze DNA methylation and various molecular biology techniques, as probe hybridization and sequencing, can be used to identify methylated cytosines in genomic DNAs treated with one of these approaches

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