Fig. 5: Impact of structural rearrangement and ecDNA amplification on enhancer connectivity.
From: Three-dimensional genome landscape of primary human cancers
a, Workflow of the joint HiChIP–WGS analysis for simple structural variants and complex focal amplifications. b, Distribution of cyclic, BFB, complex and linear somatic focal amplifications detected across 62 tumor whole-genome samples with corresponding HiChIP data and 62 patient-matched normal samples as controls. c, Distribution of cyclic, BFB, complex, linear fSCNA affecting oncogenes. d, Raw HiChIP contact matrix of ERBB2 rearrangement with tracks visualizing H3K27ac 1D signal enrichment, CN inferred from WGS, SVs identified by WGS and amplicon prediction (top). The raw, unnormalized HiChIP contact matrix allows for visualization of regions of high HiChIP signal before normalization, which correspond to amplifications and structural rearrangements detected by WGS. CN-normalized HiChIP contact matrix with tracks visualizing TADs/neoTADs, H3K27ac 1D signal enrichment and loops/neoloops (bottom). e, Raw HiChIP contact matrix of a cyclic (ecDNA-like) EGFR rearrangement with tracks visualizing H3K27ac 1D signal enrichment, CN inferred from WGS, SVs identified by WGS, amplicon prediction and co-amplification frequency across all TCGA WGS samples (top). Tracks visualizing H3K27ac 1D signal enrichment and significance of co-amplification with CN-normalized HiChIP matrix below (bottom). Arrow indicates increased interaction signal indicative of a circular amplicon. f, Violin and box plot quantifying neoloops per megabase within cyclic, BFB, complex, linear amplifications identified by NeoLoopFinder (n = number of unique amplifications). Loop counts are quantified for each focal amplification, normalized by the size of the focal amplification and classified as a neoloop if they span an SV breakpoint. P values were calculated using a two-sided Wilcoxon rank-sum test and adjusted using the BH procedure. Box centerline, median; box limits, upper and lower quartiles; box whiskers, 1.5× interquartile range. fSCNA, focal somatic CN amplifications.
