Imagine this situation with ChIP-seq analysis.
We have to conditions: A and B. For each condition there are three samples: one is ChIP, the other two are the controls (IgG and Input). For sample A the control with best quality (with higher number of reads and that passes QC) is IgG and for sample B the control with best quality is Input. If we want to compare condition A with condition B, should we use the same control in both conditions regardless of the quality of that control or can we use different controls for different conditions (IgG for A and Input for B)?