Search PubMedSearch

Biomedical subjects

Guy Baele

Publications and source records attributed to Guy Baele.

3 recordsLinked to original sources

Evolutionary history of Jamestown Canyon virus reveals complex multi-vector ecology.

Jamestown Canyon virus (JCV) is a historically understudied mosquito-borne virus of increasing concern in North America. We generated 658 whole-genome JCV sequences from northeast United States, including 84% (500/597) of all JCV-positive mosquitoes detected in Connecticut from 1997 to 2022. Then, we applied phylodynamic methods to demonstrate how mosquito phenology structures the maintenance and evolution of JCV. Our phylogenetic analyses estimate that JCV was introduced in the Northeast by at least the early 1700s, and the primary introductions of lineages A and B into Connecticut occurred during the mid-1800s to mid-1900s. Further, we estimate that JCV evolves at a rate of ∼3 × 10-5 substitutions per site per year (s/s/y), making it one of the slowest-evolving known RNA viruses, because the virus spends ∼10 months per year in evolutionary stasis while overwintering in mosquito eggs. To investigate ecological drivers of JCV spread in Connecticut, we paired discrete trait and continuous phylogeographic reconstructions with mosquito surveillance data. We estimate that JCV has a low diffusion rate of ∼30-60 km2/year, which is more similar to slow-moving tick-borne viruses than to other mosquito-borne viruses. We found that univoltine Aedes mosquitoes were likely to maintain the virus across years through overwintering in eggs, accounting for its slow evolution and dispersal, while multivoltine mosquitoes contributed to periodic bursts of spatial diffusion and amplification within seasons. We demonstrate the utility of dense sequencing and phylodynamics to disentangle complex transmission cycles, offering a framework for rapidly advancing our evolutionary and ecological knowledge of understudied viruses.

Animals

Navigating Sampling Bias in Discrete Phylogeographic Analysis: Assessing the Performance of an Adjusted Bayes Factor.

Bayesian phylogeographic inference is widely used in molecular epidemiological studies to reconstruct the dispersal history of pathogens. Discrete phylogeographic analysis treats geographic locations as discrete traits and infers lineage transition events among them, and is typically followed by a Bayes factor (BF) test to assess the statistical support. In the standard BF (BFstd) test, the relative abundance of the involved trait states is not considered, which can be problematic in the case of unbalanced sampling. Existing methods to correct sampling bias in discrete phylogeographic analyses using continuous-time Markov chain (CTMC) model, often require additional epidemiological information to balance the sampling effort among locations. As such data is not necessarily available, alternative approaches that rely solely on available genomic data are needed. In this perspective, we assess the performance of a modification of the BFstd, the adjusted Bayes factor (BFadj), which incorporates information on the relative abundance of samples by location when inferring support for transition events and root location inference without requiring additional data. Using a simulation framework, we assess the statistical performance of BFstd and BFadj under varying levels of sampling bias, estimating their type I and type II error rates. Our results show that BFadj complements the BFstd by reducing type I errors at the cost increasing type II errors for inferred transition events, while improving type I and type II errors in root location inference. Our findings provide guidelines for implementing the complementary BFadj to detect and mitigate sampling bias in discrete phylogeographic inference using CTMC modeling.

Bayes Theorem

Parallel algorithms for phylogenetic inference under a structured coalescent approximation.

While advances in molecular epidemiology and computational modeling have enhanced our capacity to track pathogen evolution, the accurate reconstruction of spatiotemporal transmission dynamics remains essential for developing epidemic preparedness frameworks and implementing outbreak response measures. Structured coalescent models offer a phylogeographic framework by restricting lineage coalescence events to geographically proximate host populations. Although the Bayesian structured coalescent approximation (BASTA) provides a tractable approach, contemporary phylogeographic analyses involving dozens of geographic localities and hundreds to thousands of viral genomes substantially exceed the computational capacity of existing implementations. The BASTA likelihood scales cubically with deme count and quadratically with sequence count due to matrix exponentiation and pairwise coalescent probability calculations. Here, we introduce a comprehensive algorithmic restructuring of the structured coalescent likelihood that eliminates redundancies, optimizes memory access, and exposes parallelization opportunities. Our approach reorganizes computations along three dimensions: (i) independent calculation of deme-transition probability matrices across time intervals; (ii) simultaneous evaluation of partial likelihood vectors within temporal slices; and (iii) concurrent aggregation of coalescent probabilities. Algorithmic restructuring cuts average coalescent likelihood computation by 7-8 fold, and parallelization further boosts performance to 10-26 fold, enabling joint phylogeographic analyses of dengue virus across 10 South American countries and H5N1 avian influenza across 20 Eurasian regions to finish in a fraction of prior time. This computational efficiency also enables comparison between backward-in-time structured coalescent approximations and forward-in-time phylogeographic methods, revealing that the former provides appropriately conservative posterior estimates, particularly at intermediate phylogenetic depths. We integrate our implementation into the popular BEAST X and BEAGLE software packages, with an accompanying interface in BEAUti X to easily set up the analyses, providing researchers with an accessible and scalable tool for real-time phylogeographic surveillance of rapidly evolving pathogens.

Journal Article