Methylating much?

Our readers might have gotten distracted this month by discussions on whether it isrightorwrongfor Illumina to limit researchers’ use of their kit, and so we are here to help you regain focus: after a deliberately thematicissue on the RBPome, we have just published an accidentally thematic issue on DNA methylation.

Useful tools

This monthGenome Biologypublishes three tools that many working on DNA methylation should find quite handy.

Mark Robinson (of edgeR, which he published together with another ofthis issue’s authors, Gordon Smyth) and company presenta new method, BayMeth, for the effective quantification of data generated with DNA-methylation-capture-seq techniques (MBD-seq, MeDIP-seq and so on). So if you want to stick to these more cost-efficient methods (than whole-genome bisulfite sequencing, BS-seq) for now, BayMeth is certainly a tool that will give you the perfect excuse to do so. But, as the authors tell us, you should be careful to include spiked methylation controls in your experiments. They also point out that BayMeth can be used as a pre-processing step for differential methylation analysis. Which swiftly takes us to the next tool: MOABS.

MOABS(or model based analysis of bisulfite sequencing data) is developed by Wei Li and colleagues from Baylor College of Medicine and designed specifically to detect differential DNA methylation with as little as 10-fold coverage, and at single CpG resolution. It is, however, not just accurate: it is fast too, and compares favorably toBSmooth, which appeared in our 2012special issue on epigenomics。MOABS can cut your costs down when you do BS-seq, but it will also help you with differential analysis of the sixth base (5hmC), through combined analysis of both BS-seq and oxBS-seq data.

source: flickr, calciostreaming (CC BY)

Finally, Stephan Beck and colleaguesdescribe a new component of the ChAMPBioconductor package that will let you use the high-density methylation arrays data for the detection of copy number changes. The researchers show that, when analyzing Infinium HumanMethylation450 BeadChip datasets with their new method, they can detect copy number alterations with the sensitivity of SNP arrays. So if you have an Infinium dataset that you hid in the bottom drawer until better times, take it out now and analyze away!

Variation of methylation

Alongside these new tools, this issue ofGenome Biologyalso includes some interesting research on (perhaps unsurprisingly) variation of DNA methylation.

To kick-off with, a group led by Wolfgang Wagner from Aachendescribes a method for tracking aging of blood。The authors do this by measuring DNA methylation at just three CpG sites. Some of our readers will find this reminiscent of Steve Horvath’s article thatGenome Biologypublished last year。While the authors did not compare their method with Horvath’s approach in their article, Steve Horvath himself did: and you can read his replyin our comments section。Importantly, while Horvath’s method tends to be more accurate – unsurprisingly, as it uses not three, but over 350 CpG sites – the approach described by Wagner and colleagues is made to be quick, robust and easy to use.

Along the same lines of DNA methylation changes with age, Andrew Jaffe and Rafael Irizarryaddress yet another issue commonly coming up in DNA methylation studies。也就是说,当研究DNA甲基化摇来摇去m blood, the results are often confounded by the cellular heterogeneity of the samples. They find that cellular composition of blood changes with age, and that these changes can explain observed variability of DNA methylation in the datasets they looked at.

In the final instalment of the DNA methylation saga this month, Tomi Pastinen, Mathieu Blanchette and their colleagues from McGill Universityreport an analysis of single-nucleotide variants, gene expression and DNA methylationin primary fibroblasts of over 60 individuals. Their study comes hot on the heels ofa paper published last summerineLife(whichwas covered byGenome Biologyin a Research Highlight by Michael Kobor). Both these articles discuss the intricate network of relationships between DNA methylation, genotype and gene expression, and the simple answer to the question of ‘what causes what’ is that there isn’t one.

And other stuff

While we like DNA methylation as much as the next person,Genome Biology’s February issue is a large one, and full of more amazing science. So whether you are intoplantsand theirlincRNAs, or蠕虫,insects, orhumans, we are sure you will find a good story for yourselves.

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