Fig. 8

SSB hotspots overlap significantly with AP site hotspots. (A) Top, the diagram showing two types of SSBs with fixed genomic positions relative to those of AP sites that are generated during the repair of the AP sites by BER. Detecting the overlap between AP site and the SSB generated by APE1 requires shifting the genomic coordinate of the AP site upstream by 1 base and is therefore denoted as “AP − 1”. Bottom, the odds ratios of genome-wide overlap between sample-shared SSB hotspots and sample-shared AP hotspots (depth ≥ 1, purple), and the average odds ratios of overlap between all SSBs and AP sites (background, green) in each tissue. The odds ratios are shown on the Y-axes in the log₂ scale. The left and right panels represent two different modes of overlap to detect the corresponding two types of SSBs shown in the top panel. (B, C) Odds ratios of enrichment (Y-axis, B) and the template vs. nontemplate ratios (Y-axis, C) of all SSB hotspots and those that overlap with AP site hotspots and found on other template or non-template strands in the indicated non-overlapping distance bins to TSSs. The red dashed horizontal lines represent odds ratios (B) or template vs. nontemplate ratio (C) of 1 that represent respectively no enrichment or no strand preference. The asterisks above the horizontal lines denote the significance of the difference: ***, **** represent respectively p-values < 0.001 and 0.0001 (Wilcoxon Rank Sum Test). (D) The sequence motifs around the sample-shared SSB hotspots that overlap with AP site hotspots genome-wide or within ± 200 bp to TSSs. The positions of the SSB hotspots are indicated by the red arrows and the corresponding overlapping AP site hotspots are highlighted. (E) Fractions of positions (Y-axis) of the SSB hotspots that overlap with AP site hotspots and map to CG dinucleotides genome-wide and within the ± 200 bp windows around TSSs. (F) Fractions of positions (Y-axis) of the SSB hotspots that map to CG dinucleotides genome-wide and within the ± 5 bp and ± 200 bp windows around TSSs. (E, F) “Backgr.” represents the background fractions of CG nucleotides in the corresponding mouse reference genomic sequence