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Scalable near-real-time Bayesian phylogenetics for outbreaks with Delphy
Patrick Varilly (Broad Institute), Mark Schifferli (Fathom (United Kingdom)), Katherine Yang (Fathom (United Kingdom)), Paul Cronan (Fathom (United Kingdom)), Ivan Specht (Broad Institute, Stanford University), Timothy Burcham (Fathom (United Kingdom)), Olivia Glennon (Fathom (United Kingdom)), Olivia Jacks (Fathom (United Kingdom)), Ellory Laning (Fathom (United Kingdom)), Libby Marrs (Fathom (United Kingdom)), Kyle Oba (Fathom (United Kingdom)), Shannon Yeung (Fathom (United Kingdom)), Karlie Wenran Zhao (Fathom (United Kingdom)), Edyth Parker (Redeemer's University), Ifeanyi F. Omah (Nnamdi Azikiwe University, University of Edinburgh), Jonathan E. Pekar (University of Edinburgh), Laura Luebbert (Broad Institute, Harvard University), Kristian G. Andersen (Scripps Research Institute), Daniel J. Park (Broad Institute), Stephen F. Schaffner (Broad Institute, Harvard University), Bronwyn L. MacInnis (Broad Institute, Harvard University), Christian Tientcha Happi (Harvard University, Redeemer's University), Jacob E. Lemieux (Broad Institute, Harvard University), Al Ozonoff (Broad Institute, Harvard University), Michael Mitzenmacher (Harvard University), Ben Fry (Fathom (United Kingdom)), Pardis Christine Sabeti (Broad Institute, Howard Hughes Medical Institute)
Résumé : 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.