Supplementary Figure 7: Hypothetical features of causal interactions mapped by PHM and CHi-C.
From: High-resolution genetic mapping of putative causal interactions between regions of open chromatin
(a), Scatterplot of CHi-C contact distance and read count that supports the contact (CHiCAGO score greater than 1). The color of each point is proportional to the CHiCAGO score. Contacts with CHiCAGO score > 10 are colored the same as a score of 10. (b), An example of causal interactions between strong enhancers found in an intergenic region. These peaks are not colocalised with any eQTLs within the 1-Mb cis window. (c), An example of mapped causal interaction starting from a strong enhancer (SE) to an active promoter (AP). For comparison, the coverage plot of H3K27ac ChIP-seq (Cell 162, 1039–1050, 2015) is shown in parallel with our ATAC-seq. Coverages are stratified by the three genotypes of the putative causal caQTL SNP (rs6454679[G > C]). The putative causal SNP exists around the summit of an ATAC peak that corresponds to the nucleosomal-depleted region between two histone modification ChIP-seq peaks. (d), Distributions of absolute effect sizes (|beta|) at peaks that are upstream caQTL peak (U; n = 3,469 peaks), downstream caQTL peak (D; n = 4,321 peaks), downstream caQTL peak labeled as an active promoter (AP; n = 309 peaks), poised promoter (PP; n = 75 peaks), strong enhancer (SE; n = 599 peaks), weak enhancer (WE; n = 483 peaks), repressed region (R; n = 1,202 peaks), transcribed region (T; n = 293 peaks) or insulator (I; n = 370 peaks). The upstream peaks were defined as peak j with PPCjk > 0.5 (or peak k with PPCkj > 0.5), and the downstream peaks were defined as peak k with PPCjk > 0.5 (or peak j with PPCkj > 0.5). Two-sided Kolmogorov–Smirnov test showed the average effect size for AP is significantly lower than that of SE (P = 3.0 × 10–12).
