Fig. 4: Probabilistic ordering reveals most likely timing of copy number and driver events in TGCT.

a Genome-wide landscape of clonal and subclonal loss of heterozygosity (LOH), gain, and homozygous deletion (HD) events in Genomics England (GEL) testicular germ cell tumour (TGCT) cohort. The y-axis corresponds to the fraction of tumours with a particular event. Events identified as enriched by our model and genes of interest within these regions are labelled. b Probabilistic ordering (left panel) of significantly enriched copy number events, whole genome duplication (WGD), and IntOGen-identified mutational drivers. A Plackett-Luce model was used to order events by sampling from all possible tumour phylogenies across the entire dataset (1000 iterations). Events are ordered along a timing scale (x-axis) from early to late by the mean value of the relative timing estimates. Horizontal lines show the range of time scale values inferred across the cohort for each event. The vertical lines and points for each event represent the mean and standard deviation for each distribution. The grey dashed vertical line represents the mean timing estimate of WGD across all samples. The proportion of these events present in different subtypes and clinical stages is shown in two central panels. Horizontal lines (right panel) indicate the minimum and maximum age of diagnosis in individuals harbouring a mutational event. The shaded grey circle indicates the median age of diagnosis corresponding to each mutational event. The dashed red line shows the median age of the cohort. c. Plackett-Luce-based probabilistic ordering of enriched events and mutational drivers only in seminomas. Seminomas were split into two groups (young-onset, late-onset; Supplementary Methods). The grey dashed vertical line represents the mean timing estimate of WGD across all samples. LOH loss of heterozygosity, NSGCT non-seminomatous germ cell tumours excluding tumours with seminomatous components, NSGCT (Sem) NSGCT with seminomatous components.