Additional file 1: of Evidence of scrapie transmission to sheep via goat milk

Schematic summary of the study. This file provides a graphical overview of the design of the pilot and milk transmission study and the overall results. (PDF 301 kb

Additional file 6 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 6. Mutational signatures in each patient: Results of mutational signature analyses before and after bootstrap

Additional file 4 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 4. Sample summary of samples with clonal expansions under selection pressure

Additional file 8 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 8. Sample summary for the comparison of the distribution of the number of SNVs detected in morphologically normal tissue, tumour tissue with low CNAs (percentage genome altered (PGA) 6 %)

Additional file 1 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 1. Sample summary

Additional file 7 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 7. Mutations in coding regions with functional significance: Functional impact was assessed using wANNOWAR [48]

Additional file 5 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 5. Proportion of epithelial and stromal contents for each morphologically normal sample

Additional file 2 of The architecture of clonal expansions in morphologically normal tissue from cancerous and non-cancerous prostates

Additional file 2: Supplementary Figure 1. Age vs number of SNVs detected for normal tissue from Prostate cancer patients and non-prostate cancer donors. For the non-cancer donors, the number of SNVs detected is remarkably consistent (range: 104 to 159), apart from one outlier from a cystoprostatectomy with an exceptionally high number of mutations (1202) that is uniquely classified as BPH. There is no significant correlation in the non-cancer donors between age and SNVs (ρ = -0.015, P = 0.98, Spearman’s correlation; this is retained even when the outlier is included: ρ = 0.49, P = 0.27). The number of SNVs detected for non-cancer patients is over 100 SNVs lower than all prostate cancer patients except for one prostate cancer outlier, even in the three samples which are of similar age to the prostate cancer cohort. Looking at only samples in the range 50-73 there is a statistically significant difference in the number of SNVs in prostate cancer vs non-prostate cancer donors (P = 0.0093; Wilcoxon rank sum test; excluding the normal outlier). Supplementary Figure 2. Example density plots of cell cultured fibroblasts and morphologically normal samples from patients where phylogenies could not be reconstructed due to only having one sample per patient or no detected clonal expansions under positive selection. They show the posterior distribution of the fraction of cells bearing a mutation, modelled by a one-dimensional Bayesian Dirichlet process [43]. The median density is indicated by the purple line and 95% confidence intervals by the blue region. The grey histogram shows the observed frequency density of mutations as a function of the fraction of cells bearing the mutation. Supplementary Figure 3. Subclonal architecture of patients with morphologically normal and matched tumour (N-T). Phylogenies revealing the relationships between clones for each case. Each coloured line represents a clone/subclone detected in a particular sample. When two or more coloured lines are together, they represent a clone that is found in all the samples represented. The length of the line is proportional to the weighted number of single nucleotide variants present in each clone; the thickness represents the clonal cell fraction associated with that clone (more detail in Additional file 3). Dotted lines are associated with samples that have no evidence of a unique sample specific clone. Supplementary Figure 4. The relationship between the clonal cell fraction (CCF) and the type of normal samples. Boxplots showing the distribution of estimated CCF for each clone detected and the type of normal sample (non-BPH normal tissue, normal tissue with BPH and BPH fibroblasts). Supplementary Table 1. Summary of patients with multiple normal samples. Patients 0006, 0007 and 0008 have multiple samples from non-BPH normal and tumour tissue and patients 0065, 0073 and 0077 have a sample from non-BPH and BPH normal tissue. Supplementary Table 2. The number of mutations in common between normal samples from the same donor. Supplementary Table 3. The mutation characteristics of three groups of samples defined by the proportion of genome affected by copy number alterations. Group 1: Tumour samples examined by Wedge et al. [30] with less than 6% of the genome affected by CNAs; Group 2: Tumour samples examined by Wedge et al. [30] with more than 6% of the genome affected by CNAs; and Group 3: normal samples examined in our study where no CNAs were detected. The median number of SNVs and indels are shown for each group

Examples of gains.

<p>Gains within the (A) q arm in Chr8, (B) focal amplifications at 7p11.2, and (C) 14p11.2. Three spatially separated regions of gain were present at 8q24.21. The chromosome gain events are represented with distinct colour blocks depending on the type of SCNA: gain (any gain in the number of normal allele copies) and amplification LOH (loss of one allele with any gain of the remaining allele). The regions of SCNA are ordered by length: top-smallest, bottom-largest. The genomic location of the MRAs and linked genes are additionally displayed.</p

Examples of minimal recurrent deletions.

<p>Deletions at (A) 6q14.3-q15, (B) 8p21.3-p21.2, (C) 10q23.31, (D) 13q14.13, (E) 14q24.1 and (F) 17q21.31. The genomic location of the MRA and linked genes are displayed. For the loss at 8p a recurrent region of homozygous loss (8:25417422–26386565) close to the MRA is indicated.</p