Driver indels detected by RNA-seq and WES in TCGA samples. Driver indels are defined as in-frame mutations in oncogene or truncations in TSGs. (A) Venn diagram showing driver indels detected exclusively by GDC's WES analysis (DNA-only), by our de novo RNA-seq analysis (RNA-only), or by both approaches (shared). (B) Comparison of VAF distributions in WES (DNA) and RNA-seq (RNA) by Mann–Whitney U P-value for driver indels in these three categories. Median VAF is shown by the red line. (C) Comparison of prevalence of elevated AEV indels in these three categories by χ2 test. (D) Tumor-purity distribution for samples containing indels in the three categories. A Kruskal–Wallis test was performed to assess their differences. (E) Top 10 most frequently mutated TSGs contributed by varying indel discovery approaches. CDKN2A (ranked top 11th) is also shown as an example for leveraging AEV for discovery owing to its more than 20-fold higher expression in tumors (Supplemental Fig. S7). (F) Top 10 most frequently mutated oncogenes. (*) TP53 was annotated as “possible oncogene” in glioblastoma multiform (GBM) and low-grade glioma (LGG) by Bailey et al. (2018). (G) Actionability of oncogenic in-frame indels based on COSMIC Actionability database.
