Fig. 3: Profiling TF-COF complex binding altered by NCVs.
From: Widespread perturbation of ETS factor binding sites in cancer
a Overview of the CASCADE method to profile TF-COF complex binding affected by NCVs (Ref - reference and Alt - alternative alleles). b Impact of TFA-BT NCVs on the recruitment of SRC1 and BRD4 to 2555 Ref/Alt NCV probes sets assayed using Jurkat T-cell nuclear extracts. Impact is quantified using -log10(p-value) of the COF recruitment to the different probe sets and the difference in PBM-determined Z-score between Ref and Alt alleles (Δz-score). P values are calculated using two-sided Student’s t-test comparing five replicates of Ref and Alt alleles. The NCVs identified as significant are highlighted in red. c Fraction of NCVs from different probe sets identified as significant by CASCADE in Jurkat and SK-MEL-28 cells. Numbers at the top of the bars indicate the number of probes tested in each set. d Number of TF-ABT NCVs leading to loss, gain, or no change (NC) (i.e., both alleles similarly recruit the COF) of recruitment for each COF tested. e Number of TFA-BT NCVs that affect the recruitment of 1 to 6 COFs. f Overlap between the number of TFA-BT NCVs significant by MPRAs and CASCADE. g UMAP clustering TFA-BT NCVs based on Δz-score for each of the six COFs tested. h UMAP depicting the MPRA expression allelic skew for each TFA-BT NCV. i NCOR recruitment motifs associated with two TFA-BT NCVs. j BRD4 and TBL1XR1 recruitment motifs associated with NCV at position chr12:120105668. Source data are provided as a Source Data file.
