Fig. 4: B-ALL patients share concordant changes in TAD activity. | Nature Communications

Fig. 4: B-ALL patients share concordant changes in TAD activity.

From: Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia

Fig. 4

a Bar plot presenting number of intra-TAD activity changes per patient pair upon relapse (abs(L2FC) > 0.25, FDR < 0.01). Bar plot shows means, bars represent standard deviation, and each point represents a patient (n = 12). b Volcano plot presenting increased, decreased, and stable TADs between diagnosis and relapse samples (red, blue, and gray respectively). c Correlation boxplots showing gene expression and chromatin accessibility changes within differential TADs (paired t test, p < 0.05) from relapse to diagnosis of 12 individual patient pairs. Significant differences were calculated by unpaired one-sided t test comparing gene expression or ATAC peaks within TADs with interactivity changes, losses, or gains, to gene expression or ATAC peaks within stable TADs(*****p < .00001). Boxplots show medians (horizontal line in each box), interquartile ranges (boxes), 1.5 interquartile (whiskers) and each point represents a gene or peak. d Hi-C contact matrices presenting a TAD decreased in activity at relapse in 4 of 12 patient pairs at the PCDH9 locus (Diagnosis, Relapse, and L2FC (Relapse/Diagnosis) from top to bottom). e Box plots demonstrating decreased PCDH9 mean TAD activity in cpm (top left), decreased gene expression in tpm (top right), decreased PCDH9 compartment Cscore (bottom left), and decreased chromatin accessibility in cpm (bottom right) in the 4 patient pairs at diagnosis and relapse. Significant differences were calculated with a paired one-sided t test comparing mean TAD activity, TPM, Cscore, and cpm between diagnosis and relapse. Boxplots show medians (horizontal line in each box), interquartile ranges (boxes), 1.5 interquartile (whiskers) and each point represents a patient with pairs connected by lines. f IGV genome browser tracks demonstrating A to B compartment switch, decreased chromatin accessibility, and decreased gene expression in the 4 patients with decreased TAD interactivity at the PCDH9 gene locus.

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