<p>Hello all, </p>

<p>I've read several papers estimating the quality of ChIP-seq and most estimate percentage of peaks that include the consensus sequence at about 50%. Having lower FDR does not improve this very dramatically (to 70% maybe). </p>

<p>So what are the high confidence peaks that do not contain the target motif? What causes them? Is there a systematic study of any sort? </p>

<p>I'd be grateful for any pointers. </p>

<p>cheers </p>

<p>Some possible explanations could be:</p>

<ol>
<li>Secondary binding/protein complexes: Another protein is binding the DNA and your ChIP:ed protein is binding to that protein.</li>
<li>Generally open chromatin: an active regulatory region (perhaps "unlocked" by a "pioneering TF") is easier to bind to in the absence of a motif.</li>
<li>Degenerate motif: there is actually a binding motif but it is relatively dissimilar from the consensus</li>
<li>Artefactual regions, see e g the "black list" here: <a href='https://sites.google.com/site/anshulkundaje/projects/blacklists'>https://sites.google.com/site/anshulkundaje/projects/blacklists</a></li>
</ol>

<p>Since you have an FDR it seems you have a control library so the following may not apply to your case but is interesting in general: even in negative control libraries, regions like transcription start sites give robust peaks: <a href='http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005241'>http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0005241</a></p>
