Fig. 1: Synergy of the five tools. | Nature Communications

Fig. 1: Synergy of the five tools.

From: A user guide for the online exploration and visualization of PCAWG data

Fig. 1

Instructions for reproducing the results shown are in Supplementary Note 2. a To obtain PCAWG BAMs, VCFs, and Analysis Working Group (AWG) files, the user selects the files desired, downloads a file manifest, and then downloads the actual data files (with authorization if needed) using the ICGC download tool. UCSC Xena, Chromothripsis Explorer, Expression Atlas, and PCAWG-Scout have each downloaded and processed the same primary analysis working group result files. b The UCSC Xena Visual Spreadsheet shows that the ERG fusion is present in 8 out of 18 PCAWG prostate adenocarcinoma samples (https://tinyurl.com/y78adbl5), as detected by the PCAWG RNA-seq and whole-genome sequencing data. Each row corresponds to a sample. Columns, starting at the left, correspond to histology, ERG gene expression, and ERG fusion based on RNA-seq data. The last three columns show structural variant calls using whole-genome DNA-seq data for ERG, TMPRSS2, and SLC45A3. c Chromothripsis Explorer provides an in-depth genome-wide view of copy number alterations and structural variations identified in the eight tumors with ERG fusion listed in b. Detailed information on total and minor copy number variations, as well as SVs, can be obtained by hovering over the elements within the Chromothripsis Explorer. Circos plot visualizations for the other 7 donors are given in Supplementary Fig. 4. d The Expression Atlas shows a heatmap of genes (rows) and tissue or disease type (columns). Here we show the expression of TMPRSS2 and SLC45A3 in healthy human tissue (top heatmap), as derived from our re-analysis of the GTEx dataset. The bottom heatmap shows expression in PCAWG data (https://tinyurl.com/y9fefymf). The human figure, called an anatomogram, shows the prostate tissue, highlighted in red. e PCAWG-Scout complements the above analysis by identifying recurrent mutational events in tumors without ERG fusion (fusion = 0). On the left is a mutation exclusivity analysis run by PCAWG-Scout (FDR-corrected Fisher’s exact test), which identifies FOXA1 (***p < 0.0005), SPOP (**p < 0.005), SYNE1 (*p < 0.05), as significantly associated with non-fusion tumors (https://tinyurl.com/qqudbkg). In the 3D protein structure of SPOP shown on the right, mutations are seen to cluster tightly around the region that overlaps with the interaction surface of PTEN. The portion of PTEN that interacts with SPOP is shown in yellow, along with the SPOP structure. Red indicates recurrent mutations in SPOP, with a brighter red indicating higher rate of recurrence.

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