Extended Data Figure 10. Enhancer redundancy as a widespread feature of developmental genes and robustness to the choice of thresholds used in the correlative approach.

(a–b) Top panels: Number of enhancers assigned to each gene through the correlative framework, with developmental TFs showing biased expression in forebrain (a, blue dots) or heart (b, orange dots) indicated. Classification of tissue-biased developmental TFs is described in Methods. Genes with at least one assigned enhancer are displayed and sorted according to the number of assigned enhancers (left to right). Bottom panels: Bar plot showing the total number of enhancers assigned to each of the TFs highlighted in the top panels. For each gene, a color code shows the number of predicted enhancers assigned to that gene in the relevant tissue (A: heart, B: forebrain) at E11.5 (dark color), in the relevant tissue at any other developmental stage included in the analysis (light color), or in any other tissue (white). (c) Estimated FDR (based on genome-wide permutations, see Methods) of observing a gene with 5 or more enhancers assigned to it, for increasingly larger correlation coefficients (0.25 to 0.75). The red solid line indicates an FDR of 0.05. The red arrow and the black dashed line highlight the lowest correlation coefficient (0.47, considering a step of 0.01) with an FDR <= 0.05 (FDR = 0.0495). (d) Number of genes showing 5 or more enhancers assigned to them, for increasingly larger correlation coefficients (0.25 to 0.75). The total number of genes (SCC >= 0.25) along with the number of genes identified using the threshold set in (c) (SCC >= 0.47) is indicated (1,276 and 1,058, respectively; see Supplementary Tables 11 and 12). (e) Bubble plot showing the number of genes with 5 or more enhancers assigned to them, at increasingly higher correlation between enhancer-promoter (x-axis) and between enhancers assigned to the same gene (y-axis). (f) Bubble plot displaying the fold-enrichment (linear) for developmental transcription factor (TF) genes among each set in (c).