Paper List
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Pharmacophore-based design by learning on voxel grids
This paper addresses the computational bottleneck and limited novelty in conventional pharmacophore-based virtual screening by introducing a voxel cap...
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CONFIDE: Hallucination Assessment for Reliable Biomolecular Structure Prediction and Design
This paper addresses the critical limitation of current protein structure prediction models (like AlphaFold3) where high-confidence scores (pLDDT) can...
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On the Approximation of Phylogenetic Distance Functions by Artificial Neural Networks
This paper addresses the core challenge of developing computationally efficient and scalable neural network architectures that can learn accurate phyl...
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EcoCast: A Spatio-Temporal Model for Continual Biodiversity and Climate Risk Forecasting
This paper addresses the critical bottleneck in conservation: the lack of timely, high-resolution, near-term forecasts of species distribution shifts ...
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Training Dynamics of Learning 3D-Rotational Equivariance
This work addresses the core dilemma of whether to use computationally expensive equivariant architectures or faster symmetry-agnostic models with dat...
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Fast and Accurate Node-Age Estimation Under Fossil Calibration Uncertainty Using the Adjusted Pairwise Likelihood
This paper addresses the dual challenge of computational inefficiency and sensitivity to fossil calibration errors in Bayesian divergence time estimat...
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Few-shot Protein Fitness Prediction via In-context Learning and Test-time Training
This paper addresses the core challenge of accurately predicting protein fitness with only a handful of experimental observations, where data collecti...
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scCluBench: Comprehensive Benchmarking of Clustering Algorithms for Single-Cell RNA Sequencing
This paper addresses the critical gap of fragmented and non-standardized benchmarking in single-cell RNA-seq clustering, which hinders objective compa...
Fast and Accurate Node-Age Estimation Under Fossil Calibration Uncertainty Using the Adjusted Pairwise Likelihood
Department of Statistics, University of Georgia, Athens, 30601, USA
The 30-Second View
IN SHORT: This paper addresses the dual challenge of computational inefficiency and sensitivity to fossil calibration errors in Bayesian divergence time estimation for large phylogenomic datasets.
Innovation (TL;DR)
- Methodology Introduces two Adjusted Pairwise Likelihood (APW) formulations (APW1 and APW2) that use asymptotic moment-matching weights to correct composite likelihoods within a Bayesian MCMC framework.
- Methodology Demonstrates that APW methods reduce computational cost by more than an order of magnitude compared to full-likelihood methods while maintaining comparable accuracy in node-age estimation.
- Methodology Shows that APW methods exhibit greater robustness to fossil misplacement and prior misspecification due to the reduced sensitivity of composite likelihoods to local calibration errors.
Key conclusions
- APW methods produce node-age estimates statistically comparable to full-likelihood methods across diverse simulation scenarios, with reduced sensitivity to local calibration errors.
- Applied to a genome-scale avian dataset, APW recovered divergence time patterns consistent with recent studies while achieving a >10x reduction in computational cost.
- The robustness of APW to fossil misplacement stems from the composite likelihood's inherent property of being less sensitive to errors in individual calibration points, as demonstrated in simulations modeling various prior misspecifications.
Abstract: Estimating divergence times from molecular sequence data is central to reconstructing the evolutionary history of lineages. Although Bayesian relaxed-clock methods provide a principled framework for incorporating fossil information, their dependence on repeated evaluations of the full phylogenetic likelihood makes them computationally demanding for large genomic datasets. Furthermore, because disagreements in divergence-time estimates often arise from uncertainty or error in fossil placement and prior specification, there is a need for methods that are both computationally efficient and robust to fossil-calibration uncertainty. In this study, we introduce fast and accurate alternatives based on the phylogenetic pairwise composite likelihood, presenting two adjusted pairwise likelihood (APW) formulations that employ asymptotic moment-matching weights to better approximate the behavior of the full likelihood within a Bayesian MCMC framework. Extensive simulations across diverse fossil-calibration scenarios show that APW methods produce node-age estimates comparable to those obtained from the full likelihood while offering greater robustness to fossil misplacement and prior misspecification, due to the reduced sensitivity of composite likelihoods to local calibration errors. Applied to a genome-scale dataset of modern birds, APW methods recover divergence time patterns consistent with recent studies, while reducing computational cost by more than an order of magnitude. Overall, our results demonstrate that adjusted pairwise likelihoods provide a calibration-robust and computationally efficient framework for Bayesian node dating, especially suited for large phylogenomic datasets and analyses in which fossil priors may be uncertain or imperfectly placed.