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Genomic Variability within an Organism Exposes Its Cell Lineage Tree

Figure 2

Simulation of MS Mutations and Reconstruction Score on Random Trees

Two types of random trees with 32 leaves were generated, and MS stepwise mutations were simulated. Results of simulations of wild-type human using different numbers of MS loci are shown. The white line marks the perfect score limit (according to the Penny and Hendy tree comparison algorithm [29]). The results show that it is possible to accurately reconstruct the correct tree for trees of depth equivalent to human newborn and mouse newborn (marked by blue and green dots, respectively) using the entire set of MS loci. A mathematical analysis proves that any tree of depth 40 (equivalent to mouse newborn) can be reconstructed with no errors. Simulations with MS mutation rates of MMR-deficient organisms demonstrate that cell lineage reconstruction is possible with as few as 800 MS loci (the white line indicates the 0.95 score). The quality of reconstruction depends on the topology of the tree and its maximal depth, which together influence the signal-to-noise ratio.

Figure 2

doi: https://doi.org/10.1371/journal.pcbi.0010050.g002