Fig. 5

Personalized gene regulatory network of MDA-MB-231. a Gene regulatory network inferred by motif-enrichment analysis from overexpressed genes (Z-score ≥ 2) of breast cancer cell line MDA-MB-231. Four master regulators are identified for this cell line: ETS1, ETV1, FOSL1, and STAT5A. The grey edges represent the link between transcription factors (TFs) and target genes (TGs) based on iRegulon analysis, while red edges indicate gain of motifs caused by the cis-GoF. All the represented TGs are over-expressed in MDA-MB-231, are associated with breast cancer, and are known cancer drivers. b A cis-GoF mutation in a distal enhancer (590 kb upstream) of the RARB gene creates a de novo AP1 binding site (resulting in a red edge between AP1 family transcription factor FOSL1 and RARB). c IGV screenshot shows that the mutation is heterozygous in MDA-MB-231 whole genome sequence data (below) and homozygous in JUN ChIP-seq data (above)