Control Types: What is copy number bias? How are we supposed to address it for ChIP-Seq?

Both ChIP-seq and the control associated with them exhibit copy number biases. Anywhere in the genome where there is copy number variation, you can see a shift in the number of reads aligning to that region. In a ChIP-seq sample, it is often difficult if not impossible to distinguish between copy number variation and changes in binding. Therefore, we need to use a control sample such as an input to correct for these copy number changes and help distinguish them from changes in binding. – answered by Tovah Markowitz, Paul Schaughency, Vishal Koparde.