Spike-ins: Can you please give me more detail on how the spike-in works?

Spike-in analysis is a method that allows for direct comparison between two ChIP-seq datasets. It is designed to adjust for global changes in binding. However, it is very sensitive to many sources of variation and does not handle small changes well. It also leads to a decrease in the amount of usable reads for a given sample as many reads will often map to the spike-in sample. For more details, see: https://pubmed.ncbi.nlm.nih.gov/25437568/. – answered by Tovah Markowitz, Paul Schaughency, Vishal Koparde