Site frequency spectrum of a rescued population under rare resistant mutations

Céline Bonnet and Hélène Leman

Stochastic Processes and their Applications, 2024, vol. 176, issue C

Abstract: The aim of this article is to study the impact of resistance acquisition on the distribution of neutral mutations in a cell population under therapeutic pressure. The cell population is modeled by a bi-type branching process. Initially, the cells all carry type 0, associated with a negative growth rate. Mutations towards type 1 are assumed to be rare and random, and lead to the survival of cells under treatment, i.e. type 1 is associated with a positive growth rate, and thus models the acquisition of a resistance. Cells also carry neutral mutations, acquired at birth and accumulated by inheritance, that do not affect their type. We describe the expectation of the ”Site Frequency Spectrum” (SFS), which is an index of neutral mutation distribution in a population, under the asymptotic of rare events of resistance acquisition and of large initial population. Precisely, we give asymptotically-equivalent expressions of the expected number of neutral mutations shared by both a small and a large number of cells. To identify the influence of relatives on the SFS, our work also lead us to study in detail subcritical binary Galton–Watson trees, where each leaf is marked with a small probability. As a by-product of this study, we thus provide the law of the generation of a randomly chosen leaf in such a Galton–Watson tree conditioned on the number of marks.

Keywords: Site Frequency Spectrum; Rescue dynamics; Sub and super-critical branching processes; Galton–Watson trees (search for similar items in EconPapers)
Date: 2024
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DOI: 10.1016/j.spa.2024.104421

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