Extended Data Fig. 3: Genomic distribution and regulatory features of baseline and treatment-induced IR-Alus.
From: Epigenetic therapy induces transcription of inverted SINEs and ADAR1 dependency
a, b, Distribution of the IR-Alu pairs based on their genomic orientation for the baseline immunogenic RNA (a) and treatment-induced immunogenic RNA (b). Arrows represent the genomic orientation (5′ to 3′) and arrow colour represent the transcriptional orientation (blue for sense and red for antisense). The number of IR-Alu pairs is represented by n. c, Distribution of Alu subfamilies from baseline immunogenic IR-Alus (n = 1,602 IR Alus), treatment-induced immunogenic IR-Alus (n = 5,199 IR Alus), and IR-Alus present in the human genome (n = 641,262 IR Alus). Odds ratio shows depletion or enrichment for each Alu subfamily (AluS, AluJ and AluY) at baseline immunogenic IR-Alus or treatment-induced immunogenic IR-Alus compared to Alu subfamily distribution of all IR-Alus present in the human genome. ****P < 0.0001, two-sided Fisher exact test. d, Profile of average CpG density 50 kb upstream and 50 kb downstream of the baseline IR-Alu pairs and all existing IR-Alu pairs in the human genome. e, Profile of average bona-fide CpG island (CGI) intersection density flanking (−50 kb/+50 kb; upstream/downstream) the treatment-induced IR-Alu pairs (n = 3,687 IR-Alu pairs, red line) and all existing IR-Alu pairs in the human genome (n = 746,470 IR-Alu pairs, blue line). For treatment-induced IR-Alu pairs, orientation was based on the transcriptional orientation in the MDA5-protected RNA-seq data. f, Profile of average CpG island intersection density flanking (−50 kb/+50 kb; upstream/downstream) the baseline IR-Alu pairs (n = 1,040 IR-Alu pairs, red line) and all existing IR-Alu pairs in the human genome (n = 746,470 IR-Alu pairs, blue line). g–i, Representative genomic tracks of treatment-induced IR-Alu pairs located at intergenic regions (g, h) and baseline IR-Alu pair located at a 3′ UTR region (i). The top four tracks represent antisense transcription (in red) and sense transcription (in blue). The bottom track represents CpG density (green). j, Schematic representation of baseline and treatment-induced immunogenic IR-Alu pairs.
