Fig. 3

Genetic and epigenetic characteristics of melanoma functional enhancers. a Distribution of the functional enhancers in different HRR types, and DEL-HRRs showed a stronger enrichment in the CRISPRi screening, p-value = 0.036, Mann–Whitney U test. b De novo mutational signature analysis of functional HRR-associated enhancers identified two predominant signatures corresponding to ultraviolet light exposure (SBS7a) and platinum treatment (SBS31). Cosine similarity values with COSMIC mutational signatures are shown. c Epigenetic features of the functional enhancers in melanoma, the upset plot represents the distribution of five epigenetic signals on the functional enhancers, the bar plot shows driver mutation types, and CRISPRi screen p-values were labeled for top enhancers. d Colocalized transcription factors at the functional enhancer regions. e Mutational spectrum and molecular classification for genomic loci of the functional enhancers based on WGS somatic mutation profiles of 137 MELA-AU cutaneous melanoma samples. The overall recurrence rate of enhancer-located HRR is shown on the side bar, the number of HRRs per patient is shown on the top bar graph, and the functional enhancers and the target genes support by HiChIP are shown on the left. Enhancers are clustered according to their HRR types, and patients are grouped based on previous molecular classification (mutant BRAF, mutant RAS, mutant NF1, and Triple-WT) defined by TCGA