Fig. 6: Increased mutational burden and genomic instability associated with R-loops were observed in human tumor samples.
From: RAD52 resolves transcription-replication conflicts to mitigate R-loop induced genome instability
a The genomic distribution of the consensus R-loop dataset as identified in Supplementary Fig. 7b. Various genomic regions are color coded according to the labels on the bottom. The expected distribution in case peaks were randomly positioned in the genome is shown for comparison. TTS and TES are significantly enriched in the R-loop dataset (P < 0.001) as determined by the Fisher’s exact test. b Circos plots showing structural variations and genomic alterations caused by breakpoints enriched in R-loop (right) forming regions versus non-R-loop regions (left). c–e Genomic windows depicting the frequencies of single nucleotide variants (SNV-left), long InDels > 1 bp (middle) and structural variants (SV-right), analyzed at R-loop vs non-R-loop across various cancer types. The horizontal coordinate represents different types of cancers and vertical coordinates represents coverage at all genomic regions, TSS and TES. Data is quantified by log fold change between mutational burden at R-loop versus non-R-loop regions. f–h Quantification of the average number of SNVs, Long indels, SVs per Mb of genome at TSS and TES in R-loop versus non-R-loop forming regions. Data are plotted as mean ± SEM; p-values calculated using unpaired two tailed t-tests. i Schematic to show the two types of TRCs: co-directional collisions (top) and Head on collision (bottom). The schematic illustration was created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license. j Quantification of the percentage of collisions occur at R-loop sites in terms of co-directional collisions and head-on collisions. Data are plotted as a bar graph with absolute percentage. (Fisher’s exact test). k Quantification of the comparison of average number of alterations per Mb of genome which are mapped to collision sites between CD and HO. Data are plotted as mean ± SEM. p-values were calculated by two-sided non-parametric Mann–Whitney test. l Quantification of the comparison of average number of alterations per Mb of genome at R-loop sites between tumors with high and low expression of RAD52. Tumors were categorized as expressing low (RAD52 low; bottom quartile) or high levels of RAD52 mRNA (RAD52 high; top quartile). Data plotted as box and whiskers. Boxes extend from the 25th to 75th percentiles, with the median displayed as a line. The whiskers mark the minimum (5th percentile) and maximum (95th percentile). (n = 95 (RAD52 high), n = 94 (RAD52 low)); p-values calculated using unpaired two tailed t-tests. Source data are provided as a Source Data file.
