Fig. 1: Multi-sample bulk sequencing encodes information on single cell lineages and single cell divisions.
From: Measuring single cell divisions in human tissues from multi-region sequencing data
a Each of the seven spatially separated tissue samples (in grey) consists of thousands to millions of cells that descended from a single most recent common ancestor (MRCA) cell. The genomic make-up of the single ancestral cell is described by the mutations clonal to the bulk sample. Those appear at high variant allele frequency in the sample (bottom-left panel, in purple). The intersection of mutations in any two bulk MRCA cells corresponds to the genomic profile of another more ancestral cell. This process continues back in time until the MRCA cell of all the sampled cells is reached. b The level of genomic variation within a growing tissue (e.g. development or cancer) is the direct consequence of mutation accumulation during cell divisions, leading to a branching structure. Importantly, the most fundamental parameters, the mutation rate μ and survival rate β of cells per division that drive this process are not directly observable. c Mutation rate per division μ and cell survival rate β leave identifiable fingerprints in the observable patterns of genetic heterogeneity within a tissue. Cell divisions occur in increments of natural numbers and thus the mutational distance between any two ancestral cells is a multiple of the mutation rate μ.
