Extended Data Fig. 2: Functional characterization for differential CREs.
a. Circle maps showing the H3K27ac ChIP-seq, ATAC-seq and RNA-seq of gradually gained CREs. b. Circle maps showing the H3K27ac ChIP-seq, ATAC-seq and RNA-seq of gradually lost CREs. c. The box plots show the expression level and chromatin activity of MYC. The scatter plots represent the correlation between the chromatin activity and gene expression of MYC among colorectal normal (n = 110, left), advanced adenoma (n = 30, middle) and cancer tissues (n = 110, right). d. The box plots show the expression and chromatin activity of SMAD4. The scatter plots represent the correlation between the chromatin activity and gene expression of SMAD4 among colorectal normal (n = 110, left), advanced adenoma (n = 30, middle) and cancer tissues (n = 110, right). e. Probability distribution density profile for the distance of differential CREs to their corresponding TSS. Each dot (red: H3K27ac ChIP signal, blue: ATAC signal) indicates a CRE plotted according to its distance to the corresponding TSS and statistical significance for differential analysis using a two-side Wald test with Benjamini-Hochberg method. f. ORs for enrichment of CREs within previously identified regulatory elements compared with non-CREs. g. OR for enrichment of CREs in CRC GWAS loci (LD r2 0.2 with index variant) compared with non-CREs. h. OR for enrichment of recurrent CREs in CRC GWAS signals (LD r2 ≥ 0.2 with index variant) compared with non-CREs. i. Pie charts show the proportion (red) of CRC GWAS loci overlapping with CRE variants from colorectal normal, advanced adenoma, and cancer tissues. j-m. Venn diagram showing the overlap of eQTLs (j), sQTLs (k), apaQTLs (l), and meQTLs (m) versus variants in CREs. For c and d, boxes indicate medians and interquartile ranges (IQRs) and whiskers indicate the minimum and maximum values. The two-sided P values were calculated by one-way ANOVA and Pearson correlation analysis. Each dot represents the OR and bars indicate 95% CIs, P-values were calculated by two-sided Fisher’s exact test (f-h).
