Single-cell mutational burden distributions in birth-death processes

Abstract

Genetic mutations are footprints of tumour growth. While mutation data in bulk samples has been used to infer evolutionary parameters hard to measure in vivo, the advent of single-cell data has led to strong interest in the mutational burden distribution (MBD) among tumour cells. We introduce dynamical matrices and recurrence relations to integrate this single-cell MBD with known statistics, and derive new analytical expressions. Surprisingly, we find that the shape of the MBD is driven by cell lineage-level stochasticity rather than by the distribution of mutations in each cell division.

28 pages, 6 figures

References in corpus (9)

• Accumulation of driver and passenger mutations during tumor progression
• Population genetics of neutral mutations in exponentially growing cancer cell populations
• Exact solution of a two-type branching process: Models of tumor progression
• Asymptotic genealogy of a critical branching process
• Exact site frequency spectra of neutrally evolving tumors: a transition between power laws reveals a signature of cell viability
• The allelic partition for coalescent point processes
• Exact solution of a two-type branching process: Clone size distribution in cell division kinetics
• Growing networks with preferential addition and deletion of edges
• Asymptotics for the site frequency spectrum associated with the genealogy of a birth and death process