Fig. 4

Several TADs genome-wide are enriched for allele-specific associations. a Illustration of ASTAD detection methodology. (i) Reference TAD domains are aligned with the raw Hi-C subtraction matrix. (ii) A median filter is applied to remove background noise and emphasize regions of consistent directional bias. (iii) The absolute sum of intra-domain allelic differences is calculated. (iv) A Z-score is calculated by comparing against the chromosome-wide background level of absolute differences for a domain of equivalent size. TADs with Z-score > 2 are considered ASTADs. b Venn diagram of conserved ASTADs between cell lines. Conserved ASTADs were defined as any set of domain intervals, between cell lines, that shared 90% reciprocal overlap. c ASTAD enrichment across different chromatin states. Chromatin states are ordered, per cell line, according to their enrichment level as determined by LOLA (max rank). ASTADs possess contrasting enrichment characteristics in H1-hESCs compared the differentiated cell lines. IMR-90 and GM12878 were significantly enriched in active chromatin relative to all TAD domains. H1-hESC were enriched for inactive and bivalent states