Extended Data Fig. 3: Quantitative analysis of TADs.
From: Heterochromatin drives compartmentalization of inverted and conventional nuclei
a, Average TADs, based on domain calls from embryonic stem cells39. Ticks indicate start and end of TADs. The visual suggestion is that TADs are weakest in rods and strongest in non-rod neurons, with wild-type and Lbr−/− thymocytes having intermediate strength. b, TAD strength is weakest in rods and strongest in non-rod neurons. TAD strength is the ratio of average contacts within the TAD (pink triangle) to average contacts between TADs (blue triangles). TAD strength is calculated separately for each autosome in two replicates. n = 38 chromosomes. Centre line is the median, the box ranges from the lower to upper quartiles and whiskers extend to 1.5× the interquartile range. c, Spearman correlation of insulation profiles across multiple mouse cell types, clustered hierarchically. Data were obtained from previous studies (GEO accession numbers GSE35156 and GSE63525)46,47, as indicated by the name of the first author in the row and column labels. ES, embryonic stem cells. d, Average insulation profile (Methods) around TAD boundaries called in embryonic stem cells39. The minimum insulation score of each profile is set to zero. We symmetrize noise by reflecting around the TAD boundary and averaging the reflected and original profiles. e, Decay of contact probability, P(s), as a function of genomic separation, s. Shaded areas are bounded by P(s) curves for biological replicas. All P(s) curves are normalized to their value at 10 kb. For rods, the steeper slope below 1 Mb and lack of a rollover in contrast to the other three cell types is indicative of weaker TADs, as previously described48. f, TAD strength as a function of cell type (columns) and cell type from which TADs are called (rows). Data were obtained from previous studies (GEO accession numbers GSE98671, GSE63525 and GSE93431)39,47,48, as indicated by the name of the first author in the row and column labels. Note that rods cluster with cell types with demonstrated weaker TADs. TAD strength is computed with the lavaburst approach (see Methods). g, Average insulation profile (Methods) oriented around the top 104 scoring CTCF motifs. For scoring, we used the FIMO algorithm49, with a position weight matrix for the M1 motif as previously described50. The minimum insulation score of each profile is set to zero, and the CTCF motif points to the left. This provides a TAD-call independent method of inferring TAD strength, given that CTCF is frequently present at the borders of TADs. h, Snapshot of HiGlass51 view of the four datasets, close to the diagonal (chromosome 12: 77,538,523–85,180,785 and chromosome 12: 79,240,367–82,837,977; 32-kb resolution). Rods almost completely lack TADs and non-rod neurons have very strong TADs, upon inspection. Datasets can be browsed in a more in-depth fashion on the HiGlass website (http://higlass.io/app/?config=JLOhiPILTmq6qDRicHMJqg).
