Figure 2. Altered chromatin accessibility landscape during OAC carcinogenesis.

(A) Schematic of ATAC-seq analysis. All peaks within ±250 kb of the TSS of a differentially expressed genes were assessed for differential accessibility between Barrett’s oesophagus and OAC. (B) Principal Component Analysis plot of log₂(1+FPKM) ATAC-seq signal from all accessible regions within ±250 kb of a differentially expressed gene TSS from all human Barrett’s oesophagus (B; n = 4) and oesophageal adenocarcinoma samples (T; n = 6). (C) Heatmap of z-score ATAC-seq signal from human Barrett’s oesophagus (B; n = 4) and OAC (T; n = 4) samples at differentially accessible regions (±2 x; Q < 0.1). Hierarchical clustering of samples and regions performed using 1-Pearson correlation. (D) Example UCSC browser view of BO, OAC and TCGA ESCA ATAC-seq data surrounding the KRT19 locus with differentially accessible regions highlighted in red. (E) Correlation plot of Pearson correlation of log₂(1+FPKM) ATAC-seq signal at differentially accessible regions. Hierarchical clustering performed using 1-Pearson correlation and the two main clusters are highlighted blue (BO) and red (OAC). TCGA samples are indicated by asterisks. See also Figure 2—figure supplement 1.

Figure 2—figure supplement 1. ATAC-seq analysis of patient OAC samples.

(A) Fragment length plot of log₁₀ transformed ATAC-seq signal from technical replicates 1 and 2 of the T_007 OAC sample (left). Correlation plot of ATAC-seq signal from technical replicates 1 and 2 of the T_007 OAC sample at ATAC-seq peaks called from replicate 1 (right). Pearson correlation coefficient is shown. (B) Fragment length plot of log₁₀ transformed ATAC-seq signal from technical replicates 1 and 2 of the T_008 OAC sample (left). Correlation plot of ATAC-seq signal from technical replicates 1 and 2 of the T_008 OAC sample at ATAC-seq peaks called from replicate 1 (right). Pearson correlation coefficient is shown. (C) Bar chart of percentage targets and percentage background of de novo discovered motifs at regions with significant decreased chromatin accessibility in OAC. De novo motifs, called transcription factor with motif match score (in brackets) and P-value are shown.