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Protocol matters: Which methylome are you actually studying?


The field of epigenetics is now capitalizing on the vast number of emerging technologies, largely based on second-generation sequencing, that interrogate DNA methylation status and histone modifications genome-wide. However, getting an exhaustive and unbiased view of a methylome at a reasonable cost is proving to be a significant challenge. In this Perspective, we take a closer look at the impact of the DNA sequence and bias effects introduced to the genome datasets from genome-wide DNA methylation technologies and where possible, explore the bioinformatics tools that deconvolute them. There remains much to be learned about the performance of genome-wide technologies, the data we mine from these assays and how it reflects the actual biology. While there are several methods to interrogate the DNA methylation status genome-wide, our opinion is that no single technique suitably covers the minimum criteria of high coverage and high resolution at a reasonable cost. In fact, which fraction of the methylome that is studied depends entirely on the inherent biases of the protocol employed. There is promise for this to change, as the third generation of sequencing technologies is expected to again ?revolutionize? the way that we study genomes and epigenomes.

Type Journal
ISBN 1750-1911
Authors Robinson, M.D.; Statham, A.L.; Speed, T.P.; Clark, S.J.
Publisher Name Epigenomics
Published Date 2010-09-01
Published Volume 2
Published Issue 4
Published Pages 587-598
Status Published in-print
DOI 10.2217/epi.10.36
OpenAccess link to author's accepted manuscript version