Site frequency spectra and estimation of clonal dynamics of tumors
We explain how models of population genetics can be used to provide quantitative inference of clonal evolution of cancer. The talk has two parts. Part 1 is devoted to the definition and mathematical properties of the Site Frequency Spectrum (SFS), one of the commonly used characteristics of cell populations undergoing growth and mutation. We explore the basic consistency of the approaches based on Wright-Fisher or Moran coalescents versus those based on birth-death processes. This provides building blocks for Part 2, which introduces the heuristic estimation equations, which employ the observable characteristics of the SFS, and allow an exact solution providing estimates of the growth and mutation rates and origin times of the clones. Examples based on simulations and available tumor data are presented. Accuracy of the estimates and their possible applications are discussed.
Contributions of Emmanuel Asante, Khanh Dinh, Roman Jaksik, Andrew Koval, Paweł Kuś, and Simon Tavaré are acknowledged.