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

Pathogen genomic analysis is central to tracking, understanding and containing outbreaks1–13, 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 phylogenetics14–17 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 datasets18–20 for efficient tree exploration and convergence. By reproducing key analyses from recent major epidemics, including Ebola1,21, Zika2, SARS-CoV-2 (ref. 22), mpox3,4 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. Delphy makes near-real-time and scalable Bayesian phylogenetics possible for growing viral outbreaks, enabling public health bodies anywhere to analyse and react to their own data with state-of-the-art accuracy and minimal friction.

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Publication Details

Journal
Nature
Published
2026-09-16
DOI
https://doi.org/10.1038/s41586-026-11012-6
Primary Topic
Genomics and Phylogenetic Studies
Type
article
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article

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

Paul Cronan, Olivia Glennon, Kristian G. Andersen, Ifeanyi F. Omah et al.
Nature
Genomics and Phylogenetic Studies
article

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

Paul Cronan, Olivia Glennon, Kristian G. Andersen, Ifeanyi F. Omah, Laura Luebbert, Jacob E. Lemieux, Ben Fry, Edyth Parker, Kyle Oba, Tim Burcham, Pardis C. Sabeti, Mark Schifferli, Bronwyn MacInnis, S. F. Schaffner, Jonathan E. Pekar, M. Mitzenmacher, Libby Marrs, Patrick Varilly, Christian Happi, Al Ozonoff, Daniel J. Park, Shannon Yeung, Olivia Jacks, Ellory Laning, Ivan Specht, Katherine Yang, Karlie Wenran Zhao
article en

Abstract

Pathogen genomic analysis is central to tracking, understanding and containing outbreaks1–13, 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 phylogenetics14–17 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 datasets18–20 for efficient tree exploration and convergence. By reproducing key analyses from recent major epidemics, including Ebola1,21, Zika2, SARS-CoV-2 (ref. 22), mpox3,4 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. Delphy makes near-real-time and scalable Bayesian phylogenetics possible for growing viral outbreaks, enabling public health bodies anywhere to analyse and react to their own data with state-of-the-art accuracy and minimal friction.

Nature
Broad Institute (US), Scripps Research Institute (US), Howard Hughes Medical Institute (US), Harvard University (US), Nnamdi Azikiwe University (NG), Redeemer's University (NG), University of Massachusetts Boston (US), Massachusetts General Hospital (US), Evolutionary Genomics (United States) (US), Institute for the Future (US), Institute of Mathematical Statistics (US), University of Edinburgh (GB)
Good health and well-being
Openalex Percentile: Top 18%
Genomics and Phylogenetic Studies
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