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Fig. 2 | Genome Medicine

Fig. 2

From: Identification of cis-regulatory mutations generating de novo edges in personalized cancer gene regulatory networks

Fig. 2

Detection of TAL1 insertion and LMO1 mutation in JURKAT cell line. a Gene regulatory network inferred from the top 500 MYB ChIP-seq peaks for the JURKAT cell line (by i-cisTarget [65]). The top enriched motifs are directly annotated for RUNX1 and MYB transcription factors (TF), which are also expressed in the JURKAT cell line. Only over-expressed target genes (TG) in JURKAT are shown (blue nodes), of which some are moreover relevant to the leukemia cancer type (green nodes) and some are known as cancer drivers (orange nodes). The grey edges represent the link between the TF and TG based on the presence of the TF motif in a MYB ChIP-seq peak near (<1 Mb) the target gene. b Non-coding mutations close to candidate target genes that are overexpressed, relevant, and drivers are tested by MotifLocator to find candidate mutations that yield a motif gain. We simulated a dataset with the JURKAT insertion upstream of TAL1 together with 67 control mutations from ten sequenced cancer cell lines (Table 1) that are found in the TAL1 locus. Out of all 68 mutations, only the JURKAT insertion showed gain of the MYB motif, which caused a new link between TAL1 and MYB (red arrow). c, d Details of the JURKAT insertion 7.5 kb upstream of the TAL1 oncogene (c) and the JURKAT SNV 4 kb upstream of the LMO1 oncogene (d), where the reference and mutated sequences are shown (the insertion/SNV is in red, the core of the motif is highlighted) together with their scores given by MotifLocator for the master MYB motifs

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