Fig. 2 | Nature Communications

Fig. 2

From: Punctuated evolution of canonical genomic aberrations in uveal melanoma

Fig. 2

BAP1 mutation diversity and necessary detection methods. Standard somatic mutation callers (i.e., Varscan2 and MuTect2) can detect SNPs (SNP) and small indels (small indel). Large indels need specialized realignment (i.e., with ABRA) for detection, as these can be missed with IndelRealigner and/or Mutect2 (large indel). Somatic mutation callers exclude germline mutations, so blood samples need to be run with a germline mutation caller (e.g., HaplotypeCaller) or as an unmatched “tumor” with a somatic caller (e.g., MuTect2) to detect patients with BAP1 hereditary cancer predisposition syndrome (germline mutation). Mutations can be “rescued” in low coverage regions by combining WES and RNA-Seq data (i.e., UNCeqR) (RNA-seq rescue). Large indels may be missed with WES data when they start or extend into intronic or promoter regions due to poor bait coverage. In the case of the former, RNA-Seq data can be used to detect large indels that start in a transcribed exon and extend into the intron using alternative splicing algorithms (RNA-seq “SpliceDel”). For the latter, WGS with alternative splicing algorithms is required to detect indels that start in the promoter region or 5′-UTR and extends into exons or across multiple exons (WGS “SpliceDel”). In cases with loss of one chromosome 3 and deletion of genes on the remaining copy of chromosome 3, a CNA caller is required to detect the homozygously deleted regions (homozygous deletion). Sample alignments were visualized using Integrative Genomics Viewer. A representative sample was selected for each mutation type and detection method

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