Abstract
Chromatin immunoprecipitation-sequencing (ChIP-seq) is widely used to find transcription factor binding sites, but suffers from various sources of noise. Knocking out the target factor mitigates noise by acting as a negative control. Paired wild-type and knockout experiments can generate improved motifs but require optimal differential analysis. We introduce peaKO—a method to automatically optimize motif analyses with knockout controls, which we compare to two other methods. PeaKO often improves elucidation of the target factor and highlights the benefits of knockout controls, which far outperform input controls. It is freely available at https://peako.hoffmanlab.org.
Competing Interest Statement
The authors have declared no competing interest.
Footnotes
↵† The authors wish it to be known that, in their opinion, the first two authors should be regarded as Joint First Authors.
Made note of non-significant p-values yielding arbitrary rankings; revised figures 2-6, to indicate the presence of non-significant results; added E-values to figures 4 and 5. Added ORCID links for each author; added to our Discussion, to better describe peaKO's utility and performance; added to Methods, to improve clarity.