Hi all, I am studying a ChIP-Seq dataset (looking at gene promoter regions in human) where it appears that different experimental groups have widely different dispersions/variances using edgeR/limma. I have 4 timepoints, and if I use edgeR to compute the dispersion for each timepoint separately, I get: 0 hours: 0.407 24 hours: 0.505 120 hours: 0.115 2 weeks: 0.0531 So the dispersion seems to range from 0.05 to 0.5. I am looking to test for "differential modification" between these timepoints, as well as between cell types at each timepoint, etc., and I was wondering if there is any differential expression test (or dispersion estimation method?) that can handle groups with different dispersions/variances. For reference, here is my experimenal design as an Excel spreadsheet: https://www.dropbox.com/s/3vnk4mai3dh39yv/chipseq-samples.xlsx And here is the result of plotBCV on each group (look at the last 4 pages for the time point groups): https://www.dropbox.com/s/s4caq1p0h3e4zhm/groupdisps.pdf (Warning: big PDF with lots of points which may bring your PDF reader to its knees.) -Ryan Thompson