Extended Data Fig. 3: Conservation score normalization and analysis including flanking wild-type blocks.
From: In vivo mapping of mutagenesis sensitivity of human enhancers
(A) Conservation score boxplots by block mutagenesis result. Centre line is median. Hinges span interquartile range (IQR). Whiskers extend from the hinge to the largest value no further than 1.5 * IQR from the hinge. (B) Same as A, but coloured by enhancer. Linear regression line is added. (C) Density of conservation scores, coloured by enhancer. Each dot in A and B is a 12 bp block (N = 167). Top panels use raw mammalian conservation score (phyloP241), bottom panels use raw score normalized for median of functional core (per enhancer). Minor loss, major loss and gain blocks were each more conserved, after median normalization, than either wild-type flanking blocks or all wild-type blocks combined. Only major loss blocks were more conserved than wild-type core blocks (FDR < 0.05, 9 comparisons, 7 significant, Mann-Whitney U-tests, two-sided). (D) Correlation between density of gnomAD variants and fraction of functional blocks in functional core (Pearson R2 = 68%, p < 0.05, cor.test in R). Related to Fig. 1. See Supplementary Tables 1 and 3 for source data.
