For a ChIP-Seq experiment with controls, MACS empirically estimates the false discovery rate (FDR) for each detected peak using the same procedure employed in the previous ChIP-chip peak finders MAT [13] and MA2C [14]. At each p-value, MACS uses the same parameters to find ChIP peaks over control and control peaks over ChIP (that is, a sample swap). The empirical FDR is defined as Number of control peaks / Number of ChIP peaks. MACS can also be applied to differential binding between two conditions by treating one of the samples as the control. Since peaks from either sample are likely to be biologically meaningful in this case, we cannot use a sample swap to calculate FDR, and the data quality of each sample needs to be evaluated against a real control.
