Extended Data Fig. 2: Comparison of methods of estimating enhancer and promoter activities and the multiplicative model.
From: Compatibility rules of human enhancer and promoter sequences
a. Intrinsic promoter activity (expression versus random genomic controls in enhancer position) of five selected promoters. Error bars: 95% CI across plasmid barcodes (n = 54-79). Promoter classes (see Methods): DNASE2 (P1), HDAC6 (P1), CD164 (P1), BCAT2 (P1), PPP1R15A (P2). b. Activation (expression versus random genomic controls in enhancer position) of 5 selected promoters by 5 selected enhancers: 1 = chr11:61602148-61602412 (E1), 2 = chr19:49467061-49467325 (E1), 3 = chrX:48641342-48641606 (E1), 4 = chr19:12893216-12893480 (E2), 5 = chr17:40851134-40851398 (E1). Error bars: 95% CI across plasmid barcodes (n = 12-56). c-d. Heatmap of promoter activity (a, expression divided by intrinsic enhancer activity) or enhancer activity (b, expression divided by intrinsic promoter activity) across all pairs of promoter (vertical) and enhancer sequences (horizontal). Axes are sorted by intrinsic promoter and enhancer activities, as in Fig. 2j. Grey: missing data. e. Intrinsic promoter and enhancer activity (y-axis, estimated by a Poisson count model) versus average pairwise Spearman correlation (as in Fig. 2c, d). f–g. Correlation between two estimates of promoter (c) and enhancer (d) activities. One method (“average activity”, x-axis) estimates activity calculated by averaging across elements, and the other method (“intrinsic activity”, y-axis) estimates activity by using coefficients estimated by a Poisson count model (see Methods). h–i. Correlation of intrinsic promoter (e) and enhancer (f) activity estimates from Poisson model using data from separate replicate experiments. j–k. Fraction of variance explained by promoter activity, enhancer activity, class interaction from the perspective of expression (STARR-seq score) and enhancer activation (fold-activation of an enhancer on a promoter, normalizing out promoter strength) limited to pairs with 2 or more (c) or 20 or more (d) plasmid barcodes. Plot includes pairs with P0 promoters and E0 enhancers. Bar plots show sequential sum of squares (Type-I ANOVA). l. Correlation of the multiplicative enhancer x promoter model with STARR-seq expression comparing enhancer-promoter pairs located within 10 kb, 100 kb, and pairs located on different chromosomes.
