arXiv subjects

Paul A. Jenkins

Publications and source records attributed to Paul A. Jenkins.

33 records · Page 2Linked to original sources

arXiv2019

A coalescent dual process for a Wright-Fisher diffusion with recombination and its application to haplotype partitioning

Duality plays an important role in population genetics. It can relate results from forwards-in-time models of allele frequency evolution with those of backwards-in-time genealogical models; a well known example is the duality between the Wright-Fisher diffusion for genetic drift and its genealogical counterpart, the coalescent. There have been a number of articles extending this relationship to include other evolutionary processes such as mutation and selection, but little has been explored for models also incorporating crossover recombination. Here, we derive from first principles a new genealogical process which is dual to a Wright-Fisher diffusion model of drift, mutation, and recombination. Our approach is based on expressing a putative duality relationship between two models via their infinitesimal generators, and then seeking an appropriate test function to ensure the validity of the duality equation. This approach is quite general, and we use it to find dualities for several important variants, including both a discrete L-locus model of a gene and a continuous model in which mutation and recombination events are scattered along the gene according to continuous distributions. As an application of our results, we derive a series expansion for the transition function of the diffusion. Finally, we study in further detail the case in which mutation is absent. Then the dual process describes the dispersal of ancestral genetic material across the ancestors of a sample. The stationary distribution of this process is of particular interest; we show how duality relates this distribution to haplotype fixation probabilities. We develop an efficient method for computing such probabilities in multilocus models.

q-bio.PE↗

arXiv2018

A Likelihood-Free Inference Framework for Population Genetic Data using Exchangeable Neural Networks

An explosion of high-throughput DNA sequencing in the past decade has led to a surge of interest in population-scale inference with whole-genome data. Recent work in population genetics has centered on designing inference methods for relatively simple model classes, and few scalable general-purpose inference techniques exist for more realistic, complex models. To achieve this, two inferential challenges need to be addressed: (1) population data are exchangeable, calling for methods that efficiently exploit the symmetries of the data, and (2) computing likelihoods is intractable as it requires integrating over a set of correlated, extremely high-dimensional latent variables. These challenges are traditionally tackled by likelihood-free methods that use scientific simulators to generate datasets and reduce them to hand-designed, permutation-invariant summary statistics, often leading to inaccurate inference. In this work, we develop an exchangeable neural network that performs summary statistic-free, likelihood-free inference. Our framework can be applied in a black-box fashion across a variety of simulation-based tasks, both within and outside biology. We demonstrate the power of our approach on the recombination hotspot testing problem, outperforming the state-of-the-art.

cs.LG↗

arXiv2018

Consistency of Bayesian nonparametric inference for discretely observed jump diffusions

We introduce verifiable criteria for weak posterior consistency of identifiable Bayesian nonparametric inference for jump diffusions with unit diffusion coefficient and uniformly Lipschitz drift and jump coefficients in arbitrary dimension. The criteria are expressed in terms of coefficients of the SDEs describing the process, and do not depend on intractable quantities such as transition densities. We also show that products of discrete net and Dirichlet mixture model priors satisfy our conditions, again under an identifiability assumption. This generalises known results by incorporating jumps into previous work on unit diffusions with uniformly Lipschitz drift coefficients.

math.ST↗

arXiv2018

Bayesian nonparametric analysis of Kingman's coalescent

Kingman's coalescent is one of the most popular models in population genetics. It describes the genealogy of a population whose genetic composition evolves in time according to the Wright-Fisher model, or suitable approximations of it belonging to the broad class of Fleming-Viot processes. Ancestral inference under Kingman's coalescent has had much attention in the literature, both in practical data analysis, and from a theoretical and methodological point of view. Given a sample of individuals taken from the population at time $t>0$, most contributions have aimed at making frequentist or Bayesian parametric inference on quantities related to the genealogy of the sample. In this paper we propose a Bayesian nonparametric predictive approach to ancestral inference. That is, under the prior assumption that the composition of the population evolves in time according to a neutral Fleming-Viot process, and given the information contained in an initial sample of $m$ individuals taken from the population at time $t>0$, we estimate quantities related to the genealogy of an additional unobservable sample of size $m^{\prime}\geq1$. As a by-product of our analysis we introduce a class of Bayesian nonparametric estimators (predictors) which can be thought of as Good-Turing type estimators for ancestral inference. The proposed approach is illustrated through an application to genetic data.

stat.ME↗

arXiv2017

Wright-Fisher diffusion bridges

{\bf Abstract} The trajectory of the frequency of an allele which begins at $x$ at time $0$ and is known to have frequency $z$ at time $T$ can be modelled by the bridge process of the Wright-Fisher diffusion. Bridges when $x=z=0$ are particularly interesting because they model the trajectory of the frequency of an allele which appears at a time, then is lost by random drift or mutation after a time $T$. The coalescent genealogy back in time of a population in a neutral Wright-Fisher diffusion process is well understood. In this paper we obtain a new interpretation of the coalescent genealogy of the population in a bridge from a time $t\in (0,T)$. In a bridge with allele frequencies of 0 at times 0 and $T$ the coalescence structure is that the population coalesces in two directions from $t$ to $0$ and $t$ to $T$ such that there is just one lineage of the allele under consideration at times $0$ and $T$. The genealogy in Wright-Fisher diffusion bridges with selection is more complex than in the neutral model, but still with the property of the population branching and coalescing in two directions from time $t\in (0,T)$. The density of the frequency of an allele at time $t$ is expressed in a way that shows coalescence in the two directions. A new algorithm for exact simulation of a neutral Wright-Fisher bridge is derived. This follows from knowing the density of the frequency in a bridge and exact simulation from the Wright-Fisher diffusion. The genealogy of the neutral Wright-Fisher bridge is also modelled by branching Pólya urns, extending a representation in a Wright-Fisher diffusion. This is a new very interesting representation that relates Wright-Fisher bridges to classical urn models in a Bayesian setting.

math.PR↗

arXiv2017

Bayesian non-parametric inference for $Λ$-coalescents: consistency and a parametric method

We investigate Bayesian non-parametric inference of the $Λ$-measure of $Λ$-coalescent processes with recurrent mutation, parametrised by probability measures on the unit interval. We give verifiable criteria on the prior for posterior consistency when observations form a time series, and prove that any non-trivial prior is inconsistent when all observations are contemporaneous. We then show that the likelihood given a data set of size $n \in \mathbb{N}$ is constant across $Λ$-measures whose leading $n - 2$ moments agree, and focus on inferring truncated sequences of moments. We provide a large class of functionals which can be extremised using finite computation given a credible region of posterior truncated moment sequences, and a pseudo-marginal Metropolis-Hastings algorithm for sampling the posterior. Finally, we compare the efficiency of the exact and noisy pseudo-marginal algorithms with and without delayed acceptance acceleration using a simulation study.

stat.ME↗

arXiv2017

Simulation from quasi-stationary distributions on reducible state spaces

Quasi-stationary distributions (QSDs)arise from stochastic processes that exhibit transient equilibrium behaviour on the way to absorption QSDs are often mathematically intractable and even drawing samples from them is not straightforward. In this paper the framework of Sequential Monte Carlo samplers is utilized to simulate QSDs and several novel resampling techniques are proposed to accommodate models with reducible state spaces, with particular focus on preserving particle diversity on discrete spaces. Finally an approach is considered to estimate eigenvalues associated with QSDs, such as the decay parameter.

stat.CO↗

arXiv2017

Inference and rare event simulation for stopped Markov processes via reverse-time sequential Monte Carlo

We present a sequential Monte Carlo algorithm for Markov chain trajectories with proposals constructed in reverse time, which is advantageous when paths are conditioned to end in a rare set. The reverse time proposal distribution is constructed by approximating the ratio of Green's functions in Nagasawa's formula. Conditioning arguments can be used to interpret these ratios as low-dimensional conditional sampling distributions of some coordinates of the process given the others. Hence the difficulty in designing SMC proposals in high dimension is greatly reduced. We illustrate our method on estimating an overflow probability in a queueing model, the probability that a diffusion follows a narrowing corridor, and the initial location of an infection in an epidemic model on a network.

stat.CO↗

arXiv2016

Poisson Random Fields for Dynamic Feature Models

We present the Wright-Fisher Indian buffet process (WF-IBP), a probabilistic model for time-dependent data assumed to have been generated by an unknown number of latent features. This model is suitable as a prior in Bayesian nonparametric feature allocation models in which the features underlying the observed data exhibit a dependency structure over time. More specifically, we establish a new framework for generating dependent Indian buffet processes, where the Poisson random field model from population genetics is used as a way of constructing dependent beta processes. Inference in the model is complex, and we describe a sophisticated Markov Chain Monte Carlo algorithm for exact posterior simulation. We apply our construction to develop a nonparametric focused topic model for collections of time-stamped text documents and test it on the full corpus of NIPS papers published from 1987 to 2015.

stat.ML↗

arXiv2015

Computational inference beyond Kingman's coalescent

Full likelihood inference under Kingman's coalescent is a computationally challenging problem to which importance sampling (IS) and the product of approximate conditionals (PAC) method have been applied successfully. Both methods can be expressed in terms of families of intractable conditional sampling distributions (CSDs), and rely on principled approximations for accurate inference. Recently, more general $Λ$- and $Ξ$-coalescents have been observed to provide better modelling fits to some genetic data sets. We derive families of approximate CSDs for finite sites $Λ$- and $Ξ$-coalescents, and use them to obtain "approximately optimal" IS and PAC algorithms for $Λ$-coalescents, yielding substantial gains in efficiency over existing methods.

math.PR↗

arXiv2015

Tractable diffusion and coalescent processes for weakly correlated loci

Widely used models in genetics include the Wright-Fisher diffusion and its moment dual, Kingman's coalescent. Each has a multilocus extension but under neither extension is the sampling distribution available in closed-form, and their computation is extremely difficult. In this paper we derive two new multilocus population genetic models, one a diffusion and the other a coalescent process, which are much simpler than the standard models, but which capture their key properties for large recombination rates. The diffusion model is based on a central limit theorem for density dependent population processes, and we show that the sampling distribution is a linear combination of moments of Gaussian distributions and hence available in closed-form. The coalescent process is based on a probabilistic coupling of the ancestral recombination graph to a simpler genealogical process which exposes the leading dynamics of the former. We further demonstrate that when we consider the sampling distribution as an asymptotic expansion in inverse powers of the recombination parameter, the sampling distributions of the new models agree with the standard ones up to the first two orders.

math.PR↗

arXiv2013

General triallelic frequency spectrum under demographic models with variable population size

It is becoming routine to obtain datasets on DNA sequence variation across several thousands of chromosomes, providing unprecedented opportunity to infer the underlying biological and demographic forces. Such data make it vital to study summary statistics which offer enough compression to be tractable, while preserving a great deal of information. One well-studied summary is the site frequency spectrum---the empirical distribution, across segregating sites, of the sample frequency of the derived allele. However, most previous theoretical work has assumed that each site has experienced at most one mutation event in its genealogical history, which becomes less tenable for very large sample sizes. In this work we obtain, in closed-form, the predicted frequency spectrum of a site that has experienced at most two mutation events, under very general assumptions about the distribution of branch lengths in the underlying coalescent tree. Among other applications, we obtain the frequency spectrum of a triallelic site in a model of historically varying population size. We demonstrate the utility of our formulas in two settings: First, we show that triallelic sites are more sensitive to the parameters of a population that has experienced historical growth, suggesting that they will have use if they can be incorporated into demographic inference. Second, we investigate a recently proposed alternative mechanism of mutation in which the two derived alleles of a triallelic site are created simultaneously within a single individual, and we develop a test to determine whether it is responsible for the excess of triallelic sites in the human genome.

q-bio.PE↗

arXiv2013

Exact simulation of the sample paths of a diffusion with a finite entrance boundary

Diffusion processes arise in many fields, and so simulating the path of a diffusion is an important problem. It is usually necessary to make some sort of approximation via model-discretization, but a recently introduced class of algorithms, known as the exact algorithm and based on retrospective rejection sampling ideas, obviate the need for such discretization. In this paper I extend the exact algorithm to apply to a class of diffusions with a finite entrance boundary. The key innovation is that for these models the Bessel process is a more suitable candidate process than the more usually chosen Brownian motion. The algorithm is illustrated by an application to a general diffusion model of population growth, where it simulates paths efficiently, while previous algorithms are impracticable.

stat.ME↗

arXiv2012

Padé approximants and exact two-locus sampling distributions

For population genetics models with recombination, obtaining an exact, analytic sampling distribution has remained a challenging open problem for several decades. Recently, a new perspective based on asymptotic series has been introduced to make progress on this problem. Specifically, closed-form expressions have been derived for the first few terms in an asymptotic expansion of the two-locus sampling distribution when the recombination rate $ρ$ is moderate to large. In this paper, a new computational technique is developed for finding the asymptotic expansion to an arbitrary order. Computation in this new approach can be automated easily. Furthermore, it is proved here that only a finite number of terms in the asymptotic expansion is needed to recover (via the method of Padé approximants) the exact two-locus sampling distribution as an analytic function of $ρ$; this function is exact for all values of $ρ\in[0,\infty)$. It is also shown that the new computational framework presented here is flexible enough to incorporate natural selection.

math.PR↗

arXiv2010

An asymptotic sampling formula for the coalescent with Recombination

Ewens sampling formula (ESF) is a one-parameter family of probability distributions with a number of intriguing combinatorial connections. This elegant closed-form formula first arose in biology as the stationary probability distribution of a sample configuration at one locus under the infinite-alleles model of mutation. Since its discovery in the early 1970s, the ESF has been used in various biological applications, and has sparked several interesting mathematical generalizations. In the population genetics community, extending the underlying random-mating model to include recombination has received much attention in the past, but no general closed-form sampling formula is currently known even for the simplest extension, that is, a model with two loci. In this paper, we show that it is possible to obtain useful closed-form results in the case the population-scaled recombination rate $ρ$ is large but not necessarily infinite. Specifically, we consider an asymptotic expansion of the two-locus sampling formula in inverse powers of $ρ$ and obtain closed-form expressions for the first few terms in the expansion. Our asymptotic sampling formula applies to arbitrary sample sizes and configurations.

math.PR↗