Open Access

n this paper we study invasion probabilities and invasion times of cooperative parasites spreading in spatially structured host populations. The spatial structure of the host population is given by a random geometric graph on [0,1]n, n∈N, with a Poisson(N)-distributed number of vertices and in which vertices are connected over an edge when they have a distance of at most rN∈Θ(Nβ−1n) for some 0<β<1 and N→∞. At a host infection many parasites are generated and parasites move along edges to neighbouring hosts. We assume that parasites have to cooperate to infect hosts, in the sense that at least two parasites need to attack a host simultaneously. We find lower and upper bounds on the invasion probability of the parasites in terms of survival probabilities of branching processes with cooperation. Furthermore, we characterize the asymptotic invasion time. An important ingredient of the proofs is a comparison with infection dynamics of cooperative parasites in host populations structured according to a complete graph, i.e. in well-mixed host populations. For these infection processes we can show that invasion probabilities are asymptotically equal to survival probabilities of branching processes with cooperation. Furthermore, we build in the proofs on techniques developed in [BP22], where an analogous invasion process has been studied for host populations structured according to a configuration model. We substantiate our results with simulations.

Therapy evasion – and subsequent disease progression – is a major challenge in current oncology. An important role in this context seems to be played by various forms of cancer cell dormancy. For example, therapy-induced dormancy, over short timescales, can create serious obstacles to aggressive treatment approaches such as chemotherapy, and long-term dormancy may lead to relapses and metastases even many years after an initially successful treatment. The underlying dormancy-related mechanisms are complex and highly diverse, so that the analysis even of basic patterns of the population-level consequences of dormancy requires abstraction and idealization, as well as the identification of the relevant specific scenarios. In this paper, we focus on a situation in which individual cancer cells may switch into and out of a dormant state both spontaneously as well as in response to treatment, and over relatively short time-spans. We introduce a mathematical ‘toy model’, based on stochastic agent-based interactions, for the dynamics of cancer cell populations involving individual short-term dormancy, and allow for a range of (multi-drug) therapy protocols. Our analysis shows that in our idealized model, even a small initial population of dormant cells can lead to therapy failure under classical (and in the absence of dormancy successful) single-drug treatments. We further investigate the effectiveness of several multidrug regimes (manipulating dormant cancer cells in specific ways) and provide some basic rules for the design of (multi-)drug treatment protocols depending on the types and parameters of dormancy mechanisms present in the population.

We determine that the continuous-state branching processes for which the genealogy, suitably time-changed, can be described by an autonomous Markov process are precisely those arising from $\alpha$-stable branching mechanisms. The random ancestral partition is then a time-changed $\Lambda$-coalescent, where $\Lambda$ is the Beta-distribution with parameters $2-\alpha$ and $\alpha$, and the time change is given by $Z^{1-\alpha}$, where $Z$ is the total population size. For $\alpha = 2$ (Feller's branching diffusion) and $\Lambda = \delta_0$ (Kingman's coalescent), this is in the spirit of (a non-spatial version of) Perkins' Disintegration Theorem. For $\alpha =1$ and $\Lambda$ the uniform distribution on $[0,1]$, this is the duality discovered by Bertoin & Le Gall (2000) between the norming of Neveu's continuous state branching process and the Bolthausen-Sznitman coalescent. We present two approaches: one, exploiting the `modified lookdown construction', draws heavily on Donnelly & Kurtz (1999); the other is based on direct calculations with generators.