Fig. 3

Tumour-informed analysis of somatic mutations and copy number alterations. A Simulated data testing the sensitivity of ACT-Discover at tumour content between 0 and 10% with differing numbers of simulated SNPs per segment. At a simulated purity of 5–10%, segments containing only 50 SNPs could be rescued using ACT-Discover. At a simulated purity of 0.1%, only segments containing 50,000 SNPs or more could be rescued. B Downsampling approach testing the sensitivity of ACT-Discover in the context of reduced effective tumour content. At simulated purity of ~ 10% (i.e. 10% PDX content), 97% of this allelic imbalance remained detectable. Even at 1% effective purity, 20% of allelic imbalance was detectable, and at 0.1% effective purity, it was still possible to detect allelic imbalance, albeit only 5%. C Number of mutations identified within each sample, coloured by whether they were identified using de novo somatic mutation calling or whether they required a tumour-informed approach, and the number of copy number alterations identified within each sample, coloured by whether they were identified using de-novo copy number calling or whether they required a haplotype-informed approach. D Copy number profiles of metastasis and three cfDNA samples of patient PANVH2. For each segment, a sample was selected that had the greatest absolute difference of BAF values to 0.5. The SNPs were then coloured based on whether they were greater than 0.5 (orange) or less or equal than 0.5 (purple). This colouring was then used for the SNPs in the segment in all other samples. It was not possible to phase SNPs coloured in grey. Segments where in at least one sample SNPs coloured in purple have BAF values greater than 0.5 can be classified as having mirrored subclonal allelic imbalance. Examples of this can be seen on chromosome 2q and 7p