Fig. 1: 3D genome architectures in T-ALLs.

PCA (upper) and unsupervised hierarchical clustering analyses (lower) of compartment, domain score (D-score), and loop (a) and gene expressions (b) in normal T cells and T-ALLs. c Association of DEGs and genomic alterations at the levels of compartment, TAD, and loop. Red, upregulated; blue, downregulated. P values were calculated using the one-sided Wilcoxon rank sum test. d A summary of DEGs and their corresponding chromatin structure changes. A or B compartments were defined by the over 70% sample majority rule. “Other” refers to those states can not be defined. e, f Left-top, heatmaps show the compartment scores for each sample across the genomic regions of the CDK6 and SOX4 loci, respectively. Bar plots on the right show the gene expression level of CDK6 and SOX4 for each sample. Left-bottom, Hi-C contact maps of the CDK6 and SOX4 loci in normal T cell and T-ALL, each condition is normalized by its cis interaction pairs; blue circles: enhanced loops in T-ALL. ATAC-seq= and ChIP-seq tracks of CTCF and H3K27ac of normal T cells and T-ALL Jurkat cells, and H3K27ac ChIP-seq tracks of case 077 are also included. Right-upper: domain scores are plotted against gene expression of CDK6 and SOX4 genes. P values were calculated using Pearson correlation. Right-lower: quantification of the domain scores across TAD region encompassing the CDK6 (normal T cells, n = 4 and T-ALL, n = 17. Sample 108 is excluded from e as it has CDK6 related translocation) and SOX4 genes in all samples (normal T cells, n = 4 and T-ALL, n = 18). Statistical significance was calculated using the two-sided t-test. In c, e, and f, data are represented as boxplots where the middle line is the median, the lower and upper hinges correspond to the first and third quartiles, the upper whisker extends from the hinge to the largest value no further than 1.5 × IQR from the hinge (where IQR is the inter-quartile range), and the lower whisker extends from the hinge to the smallest value at most 1.5 × IQR of the hinge, while data beyond the whiskers were ignored in c.