Supplementary Figure 1: chromVAR workflow

(a) First, 1) the number of fragments per peak is determined for each cell, then 2) motifs or annotations of interest are assigned to peaks, and 3) the expected fragment count per peak per cell is determined assuming identical read probability per peak for each cell with a sequencing depth matched to that cell’s observed sequencing depth. (b) A “raw deviation” is calculated for each motif or annotation feature by summing the fragments in all peaks that contain that feature, then subtracting then dividing by the expected number of fragments in all peaks containing that feature. (c) A “raw deviation” is computed for “background sets” of peaks matched in GC content and fragment count to the sets of peaks containing the features of interest. (d) The raw deviations for the background sets are used to compute a bias corrected deviation and deviation z-score for each feature. (e) Bias corrected deviations and Z-scores can be used for a variety of downstream applications.