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Biology subjects

Cappello, L.

Publications and source records attributed to Cappello, L..

3 recordsLinked to original sources

Bayesian phylodynamic inference of population dynamics with dormancy

Many organisms employ reversible dormancy, or seedbank, in response to environmental fluctuations. This life-history strategy alters fundamental eco-evolutionary forces, leading to distinct patterns of genetic diversity. Two models of dormancy have been proposed based on the average duration of dormancy relative to coalescent timescales: weak seedbank, induced by scheduled seasonality (e.g., plants, invertebrates), and strong seedbank, where individuals stochastically switch between active and dormant states (e.g., bacteria, fungi). The weak seedbank coalescent is statistically equivalent to the Kingman coalescent with a scaled mutation rate, allowing the use of existing inference methods. In contrast, the strong seedbank coalescent differs fundamentally, as only active lineages can coalesce, while dormant lineages cannot. Additionally, dormant individuals typically mutate at a slower rate than active ones. Consequently, despite the significant role of dormancy in the eco-evolutionary dynamics of many organisms, no methods currently exist for inferring population dynamics involving dormancy and associated parameters. We present a Bayesian framework for jointly inferring a latent genealogy, seedbank parameters, and evolutionary parameters from molecular sequence data under the strong seedbank coalescent. We derive the exact probability density of genealogies sampled under the strong seedbank coalescent, characterize the corresponding likelihood function, and present efficient computational algorithms for its evaluation based on our theoretical framework. We develop a tailored Markov chain Monte Carlo sampler and implement our inference framework as a package SeedbankTree within BEAST2. Our work provides both a theoretical foundation and practical inference framework for studying the population genetic and genealogical impacts of dormancy.

evolutionary biology↗

Bayesian Inference of Dependent Population Dynamics in Coalescent Models

The coalescent is a powerful statistical framework that allows us to infer past population dynamics leveraging the ancestral relationships reconstructed from sampled molecular sequence data. In many biomedical applications, such as in the study of infectious diseases, cell development, and tumorgenesis, several distinct populations share evolutionary history and therefore become dependent. The inference of such dependence is a highly important, yet a challenging problem. With advances in sequencing technologies, we are well positioned to exploit the wealth of high-resolution biological data for tackling this problem. Here, we present a novel probabilistic model that relies on jointly distributed Markov random fields. We use this model to estimate past population dynamics of dependent populations and to quantify their degree of dependence. An essential feature of our approach is the ability to track the time-varying association between the populations while making minimal assumptions on their functional shapes via Markov random field priors. We provide nonparametric estimators, extensions of our base model that integrate multiple data sources, and fast scalable inference algorithms. We test our method using simulated data under various dependent population histories and demonstrate the utility of our model in shedding light on evolutionary histories of different variants of SARS-CoV-2.

bioinformatics↗

Bayesian Estimation of Population Size Changes by Sampling Tajima’s Trees

The large state space of gene genealogies is a major hurdle for inference methods based on Kingmans coalescent. Here, we present a new Bayesian approach for inferring past population sizes which relies on a lower resolution coalescent process we refer to as \"Tajimas coalescent\". Tajimas coalescent has a drastically smaller state space, and hence it is a computationally more efficient model, than the standard Kingman coalescent. We provide a new algorithm for efficient and exact likelihood calculations for data without recombination, which exploits a directed acyclic graph and a correspondingly tailored Markov Chain Monte Carlo method. We compare the performance of our Bayesian Estimation of population size changes by Sampling Tajimas Trees (BESTT) with a popular implementation of coalescent-based inference in BEAST using simulated data and human data. We empirically demonstrate that BESTT can accurately infer effective population sizes, and it further provides an efficient alternative to the Kingmans coalescent. The algorithms described here are implemented in the R package phylodyn, which is available for download at https://github.com/JuliaPalacios/phylodyn.

genetics↗