Analysing and interpreting DNA methylation data

Bock, Christoph

doi:10.1038/nrg3273

Cited by 507 publications

(508 citation statements)

References 155 publications

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“…Analysis of bisulfite sequencing data and the subsequent tertiary analysis are a complex topic. While a full discussion is beyond the scope of this review, recent publications provide greater detail (Bock 2012;Krueger et al 2012;Baubec and Akalin 2016;Shafi et al 2017). Nonetheless, the basic steps of sequencing data analysis consist of the following: quality control, alignment, quantitation, differential methylation determination, and tertiary analysis where patterns of methylation are integrated with other forms of annotation such as genomic features, other epigenomic data (e.g., chromatin and enhancers), gene expression, and pathways.…”

Section: Bioinformaticsmentioning

confidence: 99%

“…Bisulfite conversion has created an ambiguous base at cytosines that can now be either C or T. Bismark is generally the most frequently used aligner for bisulfite sequencing data (Krueger and Andrews 2011), though other sequence aligners have been reported including BSMAP (Xi andLi 2009), BS Seeker (Chen et al 2010), and others (Bock 2012). Bisulfite sequencing alignment is computationally intensive and can take days and weeks of processing time.…”

Section: Bioinformaticsmentioning

confidence: 99%

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Analysis of DNA modifications in aging research

et al. 2018

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As geroscience research extends into the role of epigenetics in aging and age-related disease, researchers are being confronted with unfamiliar molecular techniques and data analysis methods that can be difficult to integrate into their work. In this review, we focus on the analysis of DNA modifications, namely cytosine methylation and hydroxymethylation, through nextgeneration sequencing methods. While older techniques for modification analysis performed relative quantitation across regions of the genome or examined average genome levels, these analyses lack the desired specificity, rigor, and genomic coverage to firmly establish the nature of genomic methylation patterns and their response to aging. With recent methodological advances, such as whole genome bisulfite sequencing (WGBS), bisulfite oligonucleotide capture sequencing (BOCS), and bisulfite amplicon sequencing (BSAS), cytosine modifications can now be readily analyzed with base-specific, absolute quantitation at both cytosine-guanine dinucleotide (CG) and non-CG sites throughout the genome or within specific regions of interest by next-generation sequencing. Additional advances, such as oxidative bisulfite conversion to differentiate methylation from hydroxymethylation and analysis of limited input/single-cells, have great promise for continuing to expand epigenomic capabilities. This review provides a background on DNA modifications, the current state-of-theart for sequencing methods, bioinformatics tools for converting these large data sets into biological insights, and perspectives on future directions for the field.

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Section: Bioinformaticsmentioning

confidence: 99%

Section: Bioinformaticsmentioning

confidence: 99%

Analysis of DNA modifications in aging research

et al. 2018

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“…Genome-wide data analyses, such as arrays and next-generation sequencing, have a number of intricacies regarding technical aspects such as background correction, normalization, probe design bias, annealing and so on. 48,49 Authors must describe the analysis pipeline with detail, so that it can be assessed and eventually reproduced. However, these issues may be difficult to appraise fully for the non-expert reader.…”

Section: Tissuementioning

confidence: 99%

How to interpret epigenetic association studies: a guide for clinicians

2016

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“…DNA methylation is essential for many biological processes and is found altered in a variety of human diseases (Bock, 2012). Technological advances over the past decade have enabled wholegenome bisulfite sequencing (WGBS), which has become the goldstandard approach for studying cytosine (C) methylation due to its ability to quantify methylation levels unambiguously for nearly all Cs in mammalian genomes.…”

Section: Introductionmentioning

confidence: 99%

WALT: fast and accurate read mapping for bisulfite sequencing

2016

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Summary: Whole-genome bisulfite sequencing (WGBS) has emerged as the gold-standard technique in genome-scale studies of DNA methylation. Mapping reads from WGBS requires unique considerations that make the process more time-consuming than in other sequencing applications. Typical WGBS data sets contain several hundred million reads, adding to this analysis challenge. We present the WALT tool for mapping WGBS reads. WALT uses a strategy of hashing periodic spaced seeds, which leads to significant speedup compared with the most efficient methods currently available. Although many existing WGBS mappers slow down with read length, WALT improves in speed. Importantly, these speed gains do not sacrifice accuracy.

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Analysing and interpreting DNA methylation data

Cited by 507 publications

References 155 publications

Analysis of DNA modifications in aging research

Analysis of DNA modifications in aging research

How to interpret epigenetic association studies: a guide for clinicians

WALT: fast and accurate read mapping for bisulfite sequencing

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