Is there any software that can use ATAC-seq to identify super enhancer

Question

[shangguandong1996]

Hello Everyone!

Has anyone tried to identify super-enhancers by using ATAC-seq? I am wondering whether some one can recommend some software :)

Thanks a lot in advance for your comments and ideas!

Best wishes

Guandong Shang

[ATpoint]

I kind of doubt it because the "concept" of the super enhancer was postulated as long stretches of H3K27ac near active and critical genes. There was a paper (which I cannot find now ad hoc) which showed that these long stretches are only partially populated with open chromatin regions (=ATAC-seq peaks). Hence, calling "super enhancers" from ATAC-seq appears difficult (or impossible) to me.

Edit: by reminder of jared.andrews07 it was not H3K27ac alone but rather a collection of TFs and Mediator that defined SEs in the original paper, see for a review https://www.nature.com/articles/ng.3167

In any case,

[i.sudbery]

One could imagine identifying clusters of ATAC peaks that are denser, and closer to each other than one would expect (afterall, what is a super-enhancer, other than lots of enhancers clustered close to each other), but I've not actaully heard of a tool to do it.

Answer 1

[jared.andrews07]

The original paper actually used a collection of TFs + Mediator. ROSE was not designed for H3K27ac use, though both the authors and others frequently use it. You'd likely get these same comments in review if you tried it. I actually kind of expect what you get out using ATAC would be more believable, as the default promoter exclusion settings from ROSE are rather opaque and too strict in my experience for H3K27ac.

What I mean by that is you get lots of SEs called that are caused by peaks in the promoter region that only get removed from stitching if they are fully encapsulated by the promoter region, which I think ROSE defines as +/- 2kb of the TSS by default. You often get H3K27ac peaks that hit those borders, are included in stitching, and thus included in the enhancer regions ranking.

Regardless, if you're using ROSE to do the SE calling, be sure to use an updated annotation. The ones included are from like 2011 and woefully out of date. And consider expanding your definition of a "promoter" to be a little wider to mitigate instances as described above if using H3K27ac.