Scalable near-real-time Bayesian phylogenetics for outbreaks with Delphy

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Abstract
Pathogen genomic analysis is central to tracking, understanding and containing outbreaks 1–13 , but the complexity and cost of state-of-the-art phylogenetic tools limit global access and impact. Here we introduce Delphy, an exact reformulation of Bayesian phylogenetics 14–17 designed to transform its speed, scalability and accessibility while retaining Bayesian state-of-the-art accuracy. Delphy’s central data structure, an explicit mutation-annotated tree, takes advantage of the high sequence similarity of large-scale epidemic datasets 18–20 for efficient tree exploration and convergence. By reproducing key analyses from recent major epidemics, including Ebola 1,21 , Zika 2 , SARS-CoV-2 (ref. 22 ), mpox 3,4 and H5N1 (refs. 23,24 ), we demonstrate state-of-the-art accuracy with up to 2–3 orders of magnitude improvements in speed. Assessing Delphy’s scalability, we show that a simulated dataset of 100,000 sequences can be analysed within a day. We distribute Delphy as a client-side web application that enables local, interactive analysis of raw data on the user’s machine. Delphy automatically identifies key viral lineages and mutations, as well as their emergence and prevalence through time, with quantified uncertainties grounded in Bayesian theory. Delphy establishes Bayesian phylogenetics as a fast, accessible frontline tool for future outbreak response.

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