arXiv subjects

Joel O. Wertheim

Publications and source records attributed to Joel O. Wertheim.

3 recordsLinked to original sources

arXiv2026

Early warning of Mpox outbreaks in U.S. jurisdictions using Lasso Vector Autoregression models with cross-jurisdictional lags

Mpox is an orthopoxvirus that infects humans and animals and is transmitted primarily through close physical contact. The episodic and spatially heterogeneous dynamics of Mpox transmission underscores the need for timely, area-specific forecasts to support targeted public health responses in the U.S. We develop a Vector Autoregression model with Lasso regularization (VAR-Lasso) to generate rolling two-week-ahead forecasts of weekly Mpox cases for eight high-incidence U.S. jurisdictions using national surveillance data from the Centers for Disease Control and Prevention (CDC). The VAR-Lasso model identifies significant long-lag, cross-jurisdictional predictors. For a case study in San Diego County (SDC), these statistical predictors align with phylogenetic analysis that traces a 2023 cluster in SDC to an outbreak in Illinois six months earlier. As the need for public health action is often greatest when incidence is increasing, our performance evaluation focuses on positive-slope weighted error metrics. Forecast performance of the VAR-Lasso model is compared to a uni-variate Auto-Regressive (AR) Lasso model and a naive moving-average estimate. The models are compared using slope-weighted Root Mean Squared Error (RMSE), slope-weighted Mean Absolute Error (MAE), and slope-weighted bias. Across all observations, the VAR-Lasso model reduces slope-weighted RMSE, MAE, and bias by 12%, 7%, and 66% relative to the AR model, and by 16%, 13%, and 76% relative to the naive benchmark. Our findings highlight the value of sparse multivariate time-series models that leverage cross-jurisdictional case data for early forecasting of Mpox outbreaks. Such forecasting can aid health departments in proactively providing timely resources and messaging to mitigate the risks of a future outbreak.

stat.AP↗

arXiv2023

Random-effects substitution models for phylogenetics via scalable gradient approximations

Phylogenetic and discrete-trait evolutionary inference depend heavily on an appropriate characterization of the underlying character substitution process. In this paper, we present random-effects substitution models that extend common continuous-time Markov chain models into a richer class of processes capable of capturing a wider variety of substitution dynamics. As these random-effects substitution models often require many more parameters than their usual counterparts, inference can be both statistically and computationally challenging. Thus, we also propose an efficient approach to compute an approximation to the gradient of the data likelihood with respect to all unknown substitution model parameters. We demonstrate that this approximate gradient enables scaling of sampling-based inference, namely Bayesian inference via Hamiltonian Monte Carlo, under random-effects substitution models across large trees and state-spaces. Applied to a dataset of 583 SARS-CoV-2 sequences, an HKY model with random-effects shows strong signals of nonreversibility in the substitution process, and posterior predictive model checks clearly show that it is a more adequate model than a reversible model. When analyzing the pattern of phylogeographic spread of 1441 influenza A virus (H3N2) sequences between 14 regions, a random-effects phylogeographic substitution model infers that air travel volume adequately predicts almost all dispersal rates. A random-effects state-dependent substitution model reveals no evidence for an effect of arboreality on the swimming mode in the tree frog subfamily Hylinae. Simulations reveal that random-effects substitution models can accommodate both negligible and radical departures from the underlying base substitution model. We show that our gradient-based inference approach is over an order of magnitude more time efficient than conventional approaches.

q-bio.PE↗

arXiv2012

Lineage-specific transposons drove massive gene expression recruitments during the evolution of pregnancy in mammals

A major challenge in biology is explaining how novel characters originate, however, the molecular mechanisms that underlie the emergence of evolutionary innovations are unclear. Here we show that while gene expression in the uterus evolves at a slow and relatively constant rate, it has been punctuated by periods of rapid change associated with the recruitment of thousands of genes into uterine expression during the evolution of pregnancy in mammals. We found that numerous genes and signaling pathways essential for the establishment of pregnancy and maternal-fetal communication evolved uterine expression in mammals. Remarkably the majority of genes recruited into endometrial expression have cis-regulatory elements derived from lineage-specific transposons, suggesting that that bursts of transposition facilitate adaptation and speciation through genomic and regulatory reorganization.

q-bio.PE↗