Extended Data Figure 5 : Identification and characterization of silencer cCREs

Extended Data Figure 5 | Identification and characterization of silencer cCREs

a, Line plots of average phyloP conservation scores (240-way mammalian alignment) ± 500 bp around the center of each REST+ enhancer/silencer cCRE (yellow) or REST+ silencer cCRE (purple). b, Heatscatter plot showing the distribution of distal enhancer cCREs based on their alignment across Zoonomia mammalian genomes. N1 denotes the number of species in which ≥90% of a cCRE aligns; N2 denotes the number of species in which ≤10% of a cCRE aligns. Rectangles indicate predefined groups: Group 1 (G1), highly conserved (N1 ≥ 120, N2 ≤ 25); Group 2 (G2), actively evolving (20 ≤ N1 ≤ 50, N2 ≤ 120); and Group 3 (G3), primate-specific (N1 ≤ 50, N2 ≥ 180). The percentage of cCREs in each group is indicated. c, Heatscatter plot as in panel b, but for size-matched non-cCRE regions. d, Heatscatter plot as in panel b, for REST+ enhancer/silencer cCREs. e, Heatscatter plot as in panel b, for REST+ silencer cCREs. f, Volcano plot depicting effect size versus significance of CAPRA quantifications for all cCREs. Stringent STARR silencer cCREs (p < 0.01, N = 545) are in dark blue and robust STARR silencer cCREs (p < 0.05, N = 5,396) are in light blue. P-values are calculated by the CAPRA pipeline which leverages the DESeq2 negative binomial generalized linear model g, Circle-barplots denoting the enrichment of genes near STARR silencer cCREs in gene ontology categories. Length of line denotes the log2 fold enrichment over control variants and size of the terminal circle indicates statistical significance of enrichment calculated by PantherDB using two sided Fisher’s exact test with FDR correction. Top ten groups based on fold enrichment, with at least five member genes, are shown, colored by related organ/tissue (yellow for brain, teal for kidney, gray for multiple systems). h, Heatscatter plot as in panel b, for stringent STARR silencer cCREs. i, Heatscatter plot as in panel b, for robust STARR silencer cCREs.