Fig. 7

CAPE accurately predicts the effect of mutations with the highest CAPE scores on heart enhancer activity in vivo. Schematic of the human hs1760 heart enhancer locus is shown on the top. Enhancer activity of three versions of hs1760: hs1760 wild type (WT), hs1760 with top 5% mutations including the deMs, and hs1760 with 5% random non-deM mutations in transgenic E11.5 mouse embryos are shown. Both the wild-type hs1760 enhancer sequence and hs1760 with 5% non-deM random mutations could drive LacZ expression in E11.5 mouse heart (red arrow); by contrast, the top 5% mutations including deMs could deactivate this enhancer in E11.5 mouse heart. Numbers of embryos with lacZ activity in the heart over the total number of transgenic mouse embryos screened are indicated. The graphic of the genomic coordinates with the track of sequence conservation (phyloP scores) was obtained from UCSC genome browser (http://genome.ucsc.edu/; UCSC hg19 assembly). The H3K27ac enrichment data of the human heart left ventricle was obtained from ROADMAP epigenomics project [32]. The image of the wild-type hs1760 was obtained from VISTA Enhancer Browser (https://enhancer.lbl.gov/). See Additional file 1: Figures S9-S10 for details