Extended Data Fig. 6: Interpretation of young adult HSPC phylogenies.

a, Trajectories of Nτ used as input to rsimpop for the simulations to create phylogenies in b. Note the Y axis depicting Nτ is on a log scale. b, Phylogenies created by randomly sampling 380 cells from the final full simulated population of between 100,000 cells (Phylogeny 1) and 1,000,000 cells (Phylogeny 4). Phylogenies 1 to 3 are derived from simulations of the HSC population in a 30-year-old, while phylogeny 4 is derived from a simulation of the HSC population in an 80-year-old. Each simulation has an initial Nτ of 100. In all cases Nτ is the same as the population size (N) as the generation time (τ) in all simulations is fixed at 1. The blue boxes indicate the period of time in which the population size is increased. The phylodyn trajectories to the right of each simulated phylogeny use the pattern of coalescent events to recover the input trajectories for Nτ. The blue line marks the time of change in Nτ. In all cases the initial part of the trajectory is able to correctly estimate Nτ at 100,000. However, in Phylogeny 3 where there is a complete absence of coalescent events once the population size is increased, phylodyn loses resolution and wildly overestimates the value of Nτ. c, Real trees with red boxes highlighting the last 10–20 years prior to sampling, where the relative number of coalescent events is decreased (meaning the estimated Nτ is larger).