Fig. 4: NCVs derived from highly prevalent mutational processes affect transcriptional activity and COF recruitment.
From: Widespread perturbation of ETS factor binding sites in cancer
a MPRA and CASCADE validation rates for TFA-BT NCVs associated with different mutational signatures. Only mutational signatures associated with five or more NCVs in MPRA active regions in at least one cell line are shown. Gray cells indicate mutational signatures with less than 5 NCVs in MPRA active regions in the indicated cell line. The right heatmap depicts the fraction of TFA-BT NCVs in each mutation signature that are associated with altered COF recruitment. b MPRA validation rate for NCVs associated or not with ultraviolet (UV)-light mutational signature in SK-MEL-28 cells. UV-light + NCVs (n = 967), UV-light – NCVs (n = 161). Error bars indicate the standard error of a proportion. Significance determined by two-sided Fisher’s exact test. c Mutational frequency and effect on transcriptional activity and COF binding for skin cancer TFA-BT NCVs depending on the position within the ETS motif. The top violin plot shows the log10 expression allelic skew by MPRA for NCVs affecting different positions within ETS motifs. The bottom six violin plots show the Δz-score in COF binding between the reference and the alternative allele based on the position of the NCV within the ETS motif. The median is indicated by the bold horizontal line, and the first and third quartiles are indicated by the dotted horizontal lines. The bar plot indicates the number of TFA-BT NCVs affecting each position in the ETS motif. Source data are provided as a Source Data file.
