Fig. 5: Human enhancer design.

a,b, Prediction score distribution (MEL class, n = 4,000 sequences (a) and ten selected sequences (b)) after each mutation. c, Nucleotide contribution scores of a synthetic sequence pre (top) and post (bottom) 15 mutations, with binding site names, mutation positions (dashed lines) and orders (between top and bottom plots). d, Mean luciferase signal (log₂ fold-change (FC) over Renilla) of synthetic sequences from in silico sequence evolution and genomic enhancers. e, MM001 ATAC-seq profile of three integrated EFS reporters: initial, evolved and evolved with repressor sites. Red lines, enhancer boundaries. f, DeepMEL2 prediction scores (left), luciferase activity (middle) and their correlation (right) for EFS-4 sequences. g, MM001 ATAC-seq, SOX10 and ZEB2 ChIP–seq tracks for IRF4 gene; enhancer ___location in red. h, ZEB2 ChIP–seq signal (x axis), SOX10 ChIP–seq signal (y axis) and ATAC-seq signal (colour) for top ZEB2 regions in MM001. i, In vitro and in silico saturation mutagenesis values of the IRF4 enhancer. j, Enformer predictions for EFS-4 sequences replacing IRF4 enhancer: initial score and score changes postmutations. Ref. pred., reference predictions; Alt. - ref. pred., delta alternative versus reference predictions. k, Enformer predictions per mutation step and after repressor addition for MEL EFS sequences. l, Prediction scores for top 50 DNase tracks for EFS-4 sequences. Four first tracks are foreskin melanocyte male newborn and SK-MEL-5 tracks. m, ChromBPNet ATAC MM001 (MEL) and MM047 (MES) prediction scores for EFS sequences, across mutations and postrepressor addition. n, Prediction score distribution for MEL class (n = 2,000 sequences) after motif implantation. o, Relative TF locations distribution (n = 2,000). p, Luciferase signal (log₂ FC over Renilla) comparison of motif-implanted sequences and genomic enhancers. In a,n, box plots show the median (centre line), interquartile range (box limits) and 5th and 95th percentile range (whiskers). Error bars in d,f,p denote mean standard error (n = 3 biological replicates). S, SOX10; M, MITF; T, TFAP2.