Fig. 4

Sequential CHiCAGO and Peaky fine-mapping prioritizes CCVs and target genes. a Chromatin interactions at 1p22.3 in Hs578T breast cancer cells. Topologically associating domains (TADs) are shown as horizontal gray bars above GENCODE-annotated coding (blue) and non-coding (green) genes. The VCHi-C or PCHi-C baits are depicted as black boxes. Risk signals 1 and 2 are numbered, and the CCVs within each signal are shown as colored vertical lines. The ATAC-seq track is shown as a dark blue histogram. Peaky-defined MPPC values (from specified BaitIDs) are plotted with the prioritized gene overlaid as a dark blue vertical line or prioritized CCVs overlaid as royal blue vertical lines. CHiCAGO-scored interactions for specified BaitIDs are shown as black arcs. The dashed red outline highlights the prioritized CCVs and the dashed gray outline the target gene (LMO4). b Zoomed in view of prioritized signal 2 CCVs at 1p22.3. VCHi-C baits are shown as gray bars with their fragment IDs. CCVs are shown as blue vertical lines. Black histograms denote DNase I hypersensitivity sites or ChIP-seq data for H3K4me1 and CTCF binding from HMEC cells. The dashed gray outline highlights CCV rs3008455. c Position weight matrix of the CTCF binding site from JASPAR (red arrowhead indicates the CCV position in the motif), with homology to the risk (g) and protective (a) alleles of rs3008455 colored below. d Chromatin interactions at 16q24.2 in B80T5 normal breast cells. Topologically associating domains (TADs) are shown as horizontal gray bars above GENCODE-annotated coding (blue) and non-coding (green) genes. The VCHi-C or PCHi-C baits are depicted as black boxes. CCVs are shown as red vertical lines. The ATAC-seq track is shown as a dark blue histogram. Peaky-defined MPPC values (from specified BaitIDs) are plotted with the prioritized genes overlaid as dark blue or green vertical lines and prioritized CCVs overlaid as red vertical lines. CHiCAGO-scored interactions for specified BaitIDs are shown as black arcs. The dashed red outline highlights the prioritized CCVs and the dashed gray outline the prioritized target genes (MTHFSD, FOXC2, FOXL1, and FOXC2-AS1)