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Fig. 4 | BMC Cancer

Fig. 4

From: Differential chromatin accessibility landscape of gain-of-function mutant p53 tumours

Fig. 4

Impact of differential chromatin accessibility on gene expression. a Volcano plot shows the differentially expressed genes in mutant p53 with respect to the wild-type p53 tumours. Each dot represents a gene, and the x-axis represents the log2 fold change of expression value in mutant versus wild-type p53 tumours, and the y-axis shows the -log10 adjusted p-value. The vertical and horizontal dashed lines indicate the threshold of FDR (q-value) < 0.1 and |log2FoldChange(expression)| of 1. The triangle and inverted triangle symbol indicate the known target genes regulated by mutant p53, the symbol X indicates the cancer driver genes [18]. The filled symbols indicate the genes that appeared significant in the differential accessibility analysis as well. c, d The heatmap (generated using gitools [27]) shows the list of genes that have differential accessible peaks and have expression change in the same direction (gain in accessibility with increased expression, and loss in accessibility with reduced expression). Each gene is annotated whether it overlapped with known cancer driver genes [18], appeared in either differential expression analysis (AE), differential accessibility (AO) or both, presence of predicted G-quadruplex motif, p53 response element, de novo motifs and/or known mutant p53 co-factors in the differential accessibility region. e-h The chromatin accessibility profile in mutant and wild samples p53 samples for selected genes that showed significant differential gene expression and differential chromatin accessibility peaks. The plots were generated using SparK [28], each row represents a sample, and the tracks at the bottom represents annotation of predicted enhancer regions (from GeneHancer), G-quadruplex motifs, and binding sites of known mutant p53 co-factors (See methods). The boxplot shows the expression of the gene in wild-type (W) versus mutant p53 (M) tumours for the matched samples with chromatin accessibility data and in additional TCGA samples which do not have chromatin accessibility data. Each dot represents a sample and the colour indicates the relative copy number status of the gene (− 2 deep deletion, − 1 deletion, 1 amplification, 2 high amplification) in the respective samples. The p-value was computed using the Wilcoxon rank-sum test

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