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.
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Mol Oncol
November 2024
Tianjin Cancer Institute, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin Medical University Cancer Institute and Hospital, Tianjin Medical University, China.
Early cancer diagnosis from bisulfite-treated cell-free DNA (cfDNA) fragments requires tedious data analytical procedures. Here, we present a deep-learning-based approach for early cancer interception and diagnosis (DECIDIA) that can achieve accurate cancer diagnosis exclusively from bisulfite-treated cfDNA sequencing fragments. DECIDIA relies on transformer-based representation learning of DNA fragments and weakly supervised multiple-instance learning for classification.
View Article and Find Full Text PDFMethods Mol Biol
July 2024
Australian Research Council Centres of Excellence in Plant Energy Biology and Plants for Space, School of Molecular Sciences, The University of Western Australia, Crawley, WA, Australia.
DNA methylation is a covalent modification of DNA that plays important roles in processes such as the regulation of gene expression, transcription factor binding, and suppression of transposable elements. The use of whole-genome bisulfite sequencing (WGBS) enables the genome-wide identification and quantification of DNA methylation patterns at single-base resolution and is the gold standard for the analysis of DNA methylation. However, the computational analysis of WGBS data can be particularly challenging, as many computationally intensive steps are required.
View Article and Find Full Text PDFBMC Bioinformatics
May 2021
School of Computer Science, University of Science and Technology of China, Hefei, 230027, Anhui, China.
Background: The combination of the bisulfite treatment and the next-generation sequencing is an important method for methylation analysis, and aligning the bisulfite-treated reads (BS-reads) is the critical step for the downstream applications. As bisulfite treatment reduces the complexity of the sequences, a large portion of BS-reads might be aligned to multiple locations of the reference genome ambiguously, called multireads. These multireads cannot be employed in the downstream applications since they are likely to introduce artifacts.
View Article and Find Full Text PDFBMC Gastroenterol
April 2021
Division of Gastroenterology and Hepatology, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA.
Background: Quantification of circulating organ-specific cell-free DNA (cfDNA) provides a sensitive measure of ongoing cell death that could benefit evaluation of the cholestatic liver diseases primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC), which lack reliable non-invasive biomarkers. Our goal in this pilot study was to determine whether liver-specific cfDNA levels are increased in PBC and PSC patients relative to controls and in advanced versus early disease, to evaluate their potential as novel disease biomarkers.
Methods: Peripheral blood derived bisulfite-treated DNA was PCR amplified from patients with PBC (n = 48), PSC (n = 48) and controls (n = 96) to evaluate methylation status at 16 CpG sites reported to be specifically unmethylated in liver tissue near the genes IGF2R, ITIH4 and VTN.
BMC Genomics
January 2019
Department of Animal Sciences, Wageningen University, Wageningen, The Netherlands.
Background: A widely used approach in next-generation sequencing projects is the alignment of reads to a reference genome. Despite methodological and hardware improvements which have enhanced the efficiency and accuracy of alignments, a significant percentage of reads frequently remain unmapped. Usually, unmapped reads are discarded from the analysis process, but significant biological information and insights can be uncovered from these data.
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