TF motif half-site enrichment
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6.1 years ago
varsha619 ▴ 90

Any suggestions for a good tool to identify TF binding motif half-site enrichment using ChIP-seq data? I have tried MEME and MEME-ChIP, they work well for full-site motif enrichment but not that well for half-site enrichment. Thank you!

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apa@stowers ▴ 580

Don't you already need to know the motif if you are defining a half-site? MEME doesn't search for known motifs, only does denovo discovery. You would need to use FIMO with two half-PWMs for half-site enrichment. Or perhaps, run MEME with a very low -maxw setting to force discovery of only half the motif.

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Hi, I would like to look for de novo motif half-sites, I used MEME and MEME-ChIP for this and got some half-sites though not with great p-values. I used this to run MEME MAST. Is this the standard procedure for half-site enrichment? Does FIMO work differently than mast?

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6.1 years ago
varsha619 ▴ 90

Hi, I would like to look for de novo motif half-sites, I used MEME and MEME-ChIP for this and got some half-sites though not with great p-values. I used this to run MEME MAST. Is this the standard procedure for half-site enrichment? Does FIMO work differently than mast?

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6.1 years ago
apa@stowers ▴ 580

I don't know if FIMO and MAST use the same search algorithm, but they both accomplish the same thing. MAST gives much prettier / more informative outputs than FIMO.

If you want enrichment, what is the enrichment relative to? I've done several projects where we find sets of peaks and want to know if some are using full-site or only a half-site. Our approach was to make a background by merging 10 lists of random peaks with the same width and chromosome distribution as the original. Then, search for motifs in peaks and background, apply p-value cutoff, count how many peaks had at least one match, make your 2x2 contingency table (peaks, background) x (with motif, without) and run Fisher's Exact test. A simplistic approach perhaps, but fast and useful.

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I will try that, thank you!

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