With input of the ESR1 gene in the ‘Upstream regulatory analysis’ (parameters: Tissue Type: Mammary Gland, SE-Gene Linking Strategies: Closest active, FIMO: 1e–9 and Pathway Enrichment Threshold: FDR corrected P-value < 0.001) (Supplementary Figure S1B), the output table predicted that the SEs associated with ESR1 gene were indeed occupied by estrogen receptor ERα in almost all ER-positive breast cancer cell lines (Supplementary Figure S1C). Here, ESR1 is linked to breast cancer.