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Convergence of Likelihood Ratios and Estimators for Selection in non-neutral Wright-Fisher Diffusions

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 Added by Jaromir Sant
 Publication date 2020
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and research's language is English




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A number of discrete time, finite population size models in genetics describing the dynamics of allele frequencies are known to converge (subject to suitable scaling) to a diffusion process in the infinite population limit, termed the Wright-Fisher diffusion. In this article we show that the diffusion is ergodic uniformly in the selection and mutation parameters, and that the measures induced by the solution to the stochastic differential equation are uniformly locally asymptotically normal. Subsequently these two results are used to analyse the statistical properties of the Maximum Likelihood and Bayesian estimators for the selection parameter, when both selection and mutation are acting on the population. In particular, it is shown that these estimators are uniformly over compact sets consistent, display uniform in the selection parameter asymptotic normality and convergence of moments over compact sets, and are asymptotically efficient for a suitable class of loss functions.



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The two-parameter Poisson--Dirichlet diffusion, introduced in 2009 by Petrov, extends the infinitely-many-neutral-alleles diffusion model, related to Kingmans one-parameter Poisson--Dirichlet distribution and to certain Fleming--Viot processes. The additional parameter has been shown to regulate the clustering structure of the population, but is yet to be fully understood in the way it governs the reproductive process. Here we shed some light on these dynamics by formulating a $K$-allele Wright--Fisher model for a population of size $N$, involving a uniform mutation pattern and a specific state-dependent migration mechanism. Suitably scaled, this process converges in distribution to a $K$-dimensional diffusion process as $Ntoinfty$. Moreover, the descending order statistics of the $K$-dimensional diffusion converge in distribution to the two-parameter Poisson--Dirichlet diffusion as $Ktoinfty$. The choice of the migration mechanism depends on a delicate balance between reinforcement and redistributive effects. The proof of convergence to the infinite-dimensional diffusion is nontrivial because the generators do not converge on a core. Our strategy for overcoming this complication is to prove textit{a priori} that in the limit there is no loss of mass, i.e., that, for each limit point of the sequence of finite-dimensional diffusions (after a reordering of components by size), allele frequencies sum to one.
The Wright-Fisher family of diffusion processes is a widely used class of evolutionary models. However, simulation is difficult because there is no known closed-form formula for its transition function. In this article we demonstrate that it is in fact possible to simulate exactly from a broad class of Wright-Fisher diffusion processes and their bridges. For those diffusions corresponding to reversible, neutral evolution, our key idea is to exploit an eigenfunction expansion of the transition function; this approach even applies to its infinite-dimensional analogue, the Fleming-Viot process. We then develop an exact rejection algorithm for processes with more general drift functions, including those modelling natural selection, using ideas from retrospective simulation. Our approach also yields methods for exact simulation of the moment dual of the Wright-Fisher diffusion, the ancestral process of an infinite-leaf Kingman coalescent tree. We believe our new perspective on diffusion simulation holds promise for other models admitting a transition eigenfunction expansion.
Consider a two-type Moran population of size $N$ subject to selection and mutation, which is immersed in a varying environment. The population is susceptible to exceptional changes in the environment, which accentuate the selective advantage of the fit individuals. In this setting, we show that the type-composition in the population is continuous with respect to the environment. This allows us to replace the deterministic environment by a random one, which is driven by a subordinator. Assuming that selection, mutation and the environment are weak in relation to $N$, we show that the type-frequency process, with time speed up by $N$, converges as $Ntoinfty$ to a Wright--Fisher-type SDE with a jump term modeling the effect of the environment. Next, we study the asymptotic behavior of the limiting model in the far future and in the distant past, both in the annealed and in the quenched setting. Our approach builds on the genealogical picture behind the model. The latter is described by means of an extension of the ancestral selection graph (ASG). The formal relation between forward and backward objects is given in the form of a moment duality between the type-frequency process and the line-counting process of a pruned version of the ASG. This relation yields characterizations of the annealed and the quenched moments of the asymptotic type distribution. A more involved pruning of the ASG allows us to obtain annealed and quenched results for the ancestral type distribution. In the absence of mutations, one of the types fixates and our results yield expressions for the fixation probabilities.
Using graphical methods based on a `lookdown and pruned version of the {em ancestral selection graph}, we obtain a representation of the type distribution of the ancestor in a two-type Wright-Fisher population with mutation and selection, conditional on the overall type frequency in the old population. This extends results from Lenz, Kluth, Baake, and Wakolbinger (Theor. Pop. Biol., 103 (2015), 27-37) to the case of heavy-tailed offspring, directed by a reproduction measure $Lambda$. The representation is in terms of the equilibrium tail probabilities of the line-counting process $L$ of the graph. We identify a strong pathwise Siegmund dual of $L$, and characterise the equilibrium tail probabilities of $L$ in terms of hitting probabilities of the dual process.
273 - Anthony Reveillac 2008
In this paper we give a central limit theorem for the weighted quadratic variations process of a two-parameter Brownian motion. As an application, we show that the discretized quadratic variations $sum_{i=1}^{[n s]} sum_{j=1}^{[n t]} | Delta_{i,j} Y |^2$ of a two-parameter diffusion $Y=(Y_{(s,t)})_{(s,t)in[0,1]^2}$ observed on a regular grid $G_n$ is an asymptotically normal estimator of the quadratic variation of $Y$ as $n$ goes to infinity.
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