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Best Peak Caller For Histone Modifications (Mainly H3K4Me3) Chip-Seq Datasets?

I've heard of MACS for peak/region calling of histone modification chip-seq datasets (mainly H3K4me3), but I am wondering if there is any other tool I should consider as well.

chip-seq peak-calling

5 answers

SICER is especially designed for histone marks. The recently published PeakRanger also does diffuse profiles (like histone marks) and seems interesting.

MACS is best although you can try PICS as well.

Reason for using PICS: Two binding sites are separated into two disjoint regions by PICS, whereas MACS combines these two sites into a single region. This makes PICS particularly attractive for subsequent motif based analysis.

:)

MACS is best, based on what criterion?

Personally no algorithm is based, it was my personal biased opinion. Although I also gave a second option of PICS and guess you are big fan of SICER .. :)

Personally no algorithm is best, it was my personal biased opinion. I also gave a second option of PICS and I guess you are a big fan of SICER .. :)

Haven't used SICER much really, but it does have an underlying model of histone mark enrichment (based on nucleosome spacing). CCAT is the package I've used the most for histone modifications

"Best" in terms of "user experience": having first-hand experience with your own data and liking one as the best in comparison to others.

@avilella: Well said

Sorry for being grumpy ... I guess what I was trying to say was that the answer did not address the issue of how MACS and PICS are addressing histone modification profiles specifically. This is a scenario where motif based analysis (as you suggested for PICS) is not very relevant.

Its ok Mikael, once in a while we all are grumpy :) To be honest no algorithm is perfect (as far as I know) they all have drawbacks. I agree that SICER could be a better choice depending upon what kind of biological question you want to address after marking the histone modification profiles. And, I never said you were wrong and I was right.

Friends?

Personal experience shows that MACS is not good for histones. But excellent for TFs, although not terribly sensitive.

I have not had chance to look at this yet, but RSEG looks very promising! I expect this to be good as Andrew Smith has historically produced very useful software tools, e.g. CREAD and DME.

We have also had a good experience using SICER.

Although i routinely use MACS for ChIP-seq i would not recommend its use with histone data.

Maybe you can find the answer from this article: Shirley Pepke, Barbara Wold & Ali Mortazavi, Computation for ChIP-seq and RNA-seq studies. Nature Methods 6, S22 - S32 (2009).

And this question had been discussed in SEQanswers before, just try to google "ChIP-Seq Challenge".

It would be great to be able to pull SEQanswers content in the "Related questions" area in Biostar.

I have not tried this myself, but you can have a look at the ChipSeqR Bioconductor package. There is a fairly extensive section on testing this method in the associated paper by Humburg et al. that may get to the issue of "best" peak caller for nucleosomes/histon modifications. This paper also cites two other papers by Albert et al and Kharchenko et al that are probably worth having a look at as well.

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