When we asked Cursor to explain these differences, it suggested: “When you ignore uncovered regions (using

--bg

or

--skipNA

), these regions are essentially treated as “missing data” or “no data” in the bigwig file. This means that when visualization tools like IGV display the data, they will interpolate between the nearest covered regions. This interpolation can create the appearance of a higher baseline between peaks because: 1. The visualization tool is forced to draw a continuous line between the last covered position before the gap and the first covered position after the gap 2. This interpolation can create artificial “bridges” between peaks, especially when there are multiple peaks in proximity_ 3. The interpolation doesn’t account for the true biological reality that these regions might actually have zero signal_ … The

--bga

approach (assigning zeros) is generally considered more biologically accurate for ChIP-seq and CUT&RUN data because it better represents the true absence of signal in uncovered regions, rather than creating artificial interpolated values that could be misinterpreted as background signal.” I suppose our question now is: what is the rationale for skipping zero-value bins in both pipelines, and should one consider changing the default behaviour? Many thanks for your input!