Fig. 5

Analysis of chromatin interactions identified in the HiCPlus-enhanced matrix. a We observe that the chromatin loops in HiCPlus-enhanced and real high-resolution interaction matrices are enriched for the same categories of functional elements and the enrichment level are similar. While Gaussian kernel-enhanced matrix is enriched for the same categories of elements, the levels are different from those in high-resolution Hi-C matrix. Chromatin loops were predicted by Fit-Hi-C with a stringent cutoff (q-value < 1e-06) in down-sampled Hi-C, HiCPlus-enhanced, Gaussian kernel-enhanced and real high-resolution Hi-C matrices in K562 cell line at 10 kb resolution. The functional annotations by chromHMM are downloaded from the Roadmap project. Enrichment levels are computed as fold change (log2 converted) against their distribution across the whole genome. b ROC analysis of overlaps between interactions from CTCF ChIA-PET with identified interacting peaks from down-sampled Hi-C, HiCPlus-enhanced, Gaussian kernel-enhanced and real high-resolution Hi-C matrices in K562 cell line. c Percentage of CTCF ChIA-PET peaks that overlap with chromatin interactions identified in real high-resolution, down-sampled and HiCPlus-enhanced matrices. d HiCPlus-enhanced matrix captures interactions between MYC promoter and cis-regulatory elements that are missed or unresolved by low-resolution Hi-C matrix. The top two virtual 4C tracks are generated using HiCPlus-enhanced matrix (10 kb resolution) and the original matrix (40Kb resolution) from aorta tissue, anchored on MYC promoter (marked by asterisk). We compared virtual 4C tracks with Capture Hi-C data in the same region, supported by at least 20 reads in GM12878 cells. Red dots indicate the Capture Hi-C peaks that are also detected by Hi-C. We notice that multiple Capture Hi-C interactions are mapped to the same 40 kb bin and thus unresolvable by the low-resolution Hi-C matrix (yellow dots in the low-resolution virtual 4C). However, these interactions are captured by the HiCPlus-enhanced matrix. We also notice that these interactions are between MYC promoter and potential distal enhancers, marked by H3K4me1 and H3K27ac