Phylogenetic Quantification of Intra-tumour Heterogeneity
Figure 5
MEDICC quantifies heterogeneity from the locations of genomes on the mutational landscape.
A) If no or a homogeneous selection pressure is applied, cells proliferate and die randomly across the mutational landscape, leaving the surviving cells spatially unclustered. B) If the fitness landscape favours specific mutations (blue shaded areas), genomes inside those areas are more likely to survive, those outside more likely to die. The ability of a tumour for a clonal expansion into distant fitness pockets depends on its mutation potential per generation (long orange arrow). This leads to C) a situation where distinct subpopulations/clonal expansions are present in a tumour, indicating a generally high potential for a tumour to adapt to changing environments. D) The mutational landscape additionally allows estimates of average distance between two subgroups of samples, here before (blue) and after (orange) chemotherapy. The distance between the two subgroups is defined as the distance of the robust centres of mass (blue and orange X). This robust centre of mass is computed omitting the single most distant point of each subgroup (blue and orange samples in the orange and blue subgroups respectively), making the statistic more resistant towards outliers.