Figure 2
From: Modelling mutational landscapes of human cancers in vitro
Analysis of mutation signatures derived from exome data obtained from MEF immortalised cell lines.
(a) Principal component analysis (PCA) of WES data using mutation signatures. PCA was computed using as input the frequency matrices of sequence context mutations (96 variables) from cell lines immortalised following exposure of primary Hupki MEFs to a carcinogen (AA, BaP, MNNG or UVC), from Hupki MEFs carrying the AID transgene (HxAID-Tg) or from Hupki MEF-derived cell lines that immortalised spontaneously (Spont). Each sample is plotted considering the value of the first and second principal components (PC1 and PC2). The percentage of variance explained by each component is indicated within brackets in each axis. A 95% confidence ellipsis is drawn for each experimental condition and the empty squares indicate the respective centre of gravity. Cells and samples are represented by round and squared solid symbols, respectively. (b) Same as in (a) but with the human tumour datasets (same as shown in Figure 1) added to the input and labelled by arrows. HxAID-Tg samples are omitted in (b) as no corresponding relevant tumour data were identified. AAN_UTUC, aristolochic acid nephropathy-related upper urinary tract urothelial carcinoma; GBM_TZM, glioblastoma after temozolomide treatment; Lung_Ca, lung carcinoma; Skin_SCC, skin squamous cell carcinoma. (c) Graphical representation of the similarity distance of each of the six MEF signatures (front-back axis) to each of the 27 human cancer signatures2 (horizontal axis, 1A through U2). The vertical axis measures the similarity of signatures between the two systems, expressed as negative log(tan(angle), see Methods. Negative values below the x-z plane correspond to angles >45° and represent dissimilarity and are thus not shown.
