Reference Background for TF Motif Enrichment Analysis

Question

[dalia.halawani12]

Hi All,

We performed TF motif enrichment analysis on 5hmc peaks using two types of background. In the first, we used MEME AME control shuffle as a reference background. In the second, we used HOMER TF randomly selected genomic sequences with match GC content as a background. The TF enrichment results were very different with little overlap. Do you have any insight on what is going on and which method would be more preferable?

Thank you for your insights. Dalia