Figure 4.
Differential chromatin accessibility, motif, and gene expression analysis of PNR and PS leukemia. (A) Volcano plot comparing chromatin accessibility between PNR and PS leukemias. PNR and PS defining accessible regions (n = 2128) were determined by an FDR ≤ 0.5. (B) Heatmap depicting ATAC-seq peaks by sample at accessible regions shared and regions defining leukemias from PNR and PS. (C) GSEA shows increased accessibility at regions known to be active in embryonic and cancer stem cells in PNR. (D) GSEA shows decreased accessibility at regions known to be repressed in embryonic and cancer stem cells in PNR. (E) Heatmap showing the area under the receiver operating characteristic (AUROC) for key motif enrichment in regions whose accessibility was specific to leukemia cells, as determined by MEDEA.26 (F) Box plots showing increased RNA expression of the indicated TFs, measured for each leukemia sample as the Z-score of CPM (counts per million reads) values against 53 normal human tissues profiled by the GTeX consortium. Each of the presented TFs is both upregulated and known to bind to one of the motifs enriched in PNR leukemias. NS, not significant; ∗∗P ≤ .01; ∗P ≤ .05.

Differential chromatin accessibility, motif, and gene expression analysis of PNR and PS leukemia. (A) Volcano plot comparing chromatin accessibility between PNR and PS leukemias. PNR and PS defining accessible regions (n = 2128) were determined by an FDR ≤ 0.5. (B) Heatmap depicting ATAC-seq peaks by sample at accessible regions shared and regions defining leukemias from PNR and PS. (C) GSEA shows increased accessibility at regions known to be active in embryonic and cancer stem cells in PNR. (D) GSEA shows decreased accessibility at regions known to be repressed in embryonic and cancer stem cells in PNR. (E) Heatmap showing the area under the receiver operating characteristic (AUROC) for key motif enrichment in regions whose accessibility was specific to leukemia cells, as determined by MEDEA.26 (F) Box plots showing increased RNA expression of the indicated TFs, measured for each leukemia sample as the Z-score of CPM (counts per million reads) values against 53 normal human tissues profiled by the GTeX consortium. Each of the presented TFs is both upregulated and known to bind to one of the motifs enriched in PNR leukemias. NS, not significant; ∗∗P ≤ .01; ∗P ≤ .05.

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