Fig. 3

TERT mutation identification through a personalized gene regulatory network of TCGA-EE-A2M6. a Gene regulatory network inferred by iRegulon analysis from overexpressed genes (Z-score ≥ 1) of melanoma sample TCGA-EE-A2M6. Among the enriched motifs are directly annotated motifs for ETS transcription factors (TF; ELF1, ETS1), BRCA1, E2F family TFs (E2F1, E2F3, TFDP1, TFDP2), RB1, and SETDB1 (for simplicity the network is drawn only with cancer driver TFs; for a full list of predicted master regulators for this sample see Additional file 1: Table S1). The grey edges represent the link between TFs and target genes (TG) based on iRegulon analysis, while red edges indicate gain of ETS motif caused by the TERT promoter mutations C228T and C229T. All the represented TGs are overexpressed in TCGA-EE-A2M6, associated with melanoma, and known cancer drivers. bSummary table for μ-cisTarget analysis on three melanoma whole genomes. In each case μ-cisTarget results in a manageable number of candidate cis-GoF mutations including the TERT promoter mutation.c Detail of the mutation at the TERT promoter, where the reference and mutated sequences are shown (the mutation in red, the core of the motif highlighted) together with their scores given by MotifLocator for the swissregulon__hs__ELF1_2_4.p2 motif (which is directly annotated to ELF1, ELF2, and ELF4)