How can I find motifs under individual ATAC-peaks?

Question

[a.rex]

I have a IGV track image of ATAC-seq data. I was wondering - how do people look for motif enrichment under specific high ATAC-peaks? Do I have to give the entire genome to Homer (et al.) to find motifs enriched in all peaks. Then specifically try and find what motif is under my peak of interest?

Answer 1

[jared.andrews07]

The MEME suite provides both motif scanning and motif enrichment tools (among many others). It's probably the most comprehensive motif toolset out there, imo.

Motif scanning inherently yields a lot of false positives, so your region will likely have many motifs pop up as significant almost no matter what you use. Correlating with TF expression can help narrow down to those that might actually have function.

Answer 2

[Chris Miller]

This tool accepts a peak file, and looks for enriched motifs under those peaks: http://homer.ucsd.edu/homer/ngs/peakMotifs.html

Answer 3

[Charles Warden]

I've also used HOMER to define motifs within ATAC-Seq peaks. However, enrichment of some broader annotations (such as DNase experiments) may also be useful.

Depending upon your reference sequence, you may find i-cisTarget to be useful for enrichment of .bed files for peaks of interest.

Or, if you have pre-defined promoter regions, you could try using gene expression enrichment programs (at the gene symbol level), such as Enrichr, GATHER, etc. Enrichr includes ChIP-Seq binding gene lists, and GATHER has some TRANSFAC motifs (but for genes, not specific coordinates).

Answer 4

[gable_works]

I've had success with RGT-HINT which provides a motif enrichment tool. In addition the .bed file produced can be dropped into a genome browser with labeled 'motif matches'. That way you can visualized these matches at your peak of interest.