Fast and Accurate Maximum-Likelihood Estimation of Multi-Type Birth-Death Epidemiological Models from Phylogenetic Trees
Résumé
Multi-type birth-death (MTBD) models are phylodynamic analogies of compartmental models in classi-
cal epidemiology. They serve to infer such epidemiological parameters as the average number of secondary
infections Re and the infectious time from a phylogenetic tree (a genealogy of pathogen sequences). The repre-
sentatives of this model family focus on various aspects of pathogen epidemics. For instance, the birth-death
exposed-infectious (BDEI) model describes the transmission of pathogens featuring an incubation period
(when there is a delay between the moment of infection and becoming infectious, as for Ebola and SARS-
CoV-2), and permits its estimation along with other parameters.
With constantly growing sequencing data, MTBD models should be extremely useful for unravelling in-
formation on pathogen epidemics. However, existing implementations of these models in a phylodynamic
framework have not yet caught up with the sequencing speed. Computing time and numerical instability
issues limit their applicability to medium data sets (≤ 500 samples), while the accuracy of estimations should
increase with more data.
We propose a new highly parallelizable formulation of ordinary differential equations for MTBD models.
We also extend them to forests to represent situations when a (sub-)epidemic started from several cases
(e.g., multiple introductions to a country). We implemented it for the BDEI model in a maximum likeli-
hood framework using a combination of numerical analysis methods for efficient equation resolution. Our
implementation estimates epidemiological parameter values and their confidence intervals in two minutes on
a phylogenetic tree of 10 000 samples. Comparison to the existing implementations on simulated data shows
that it is not only much faster, but also more accurate. An application of our tool to the 2014 Ebola epidemic
in Sierra-Leone is also convincing, with very fast calculation and precise estimates. As MTBD models are
closely related to Cladogenetic State Speciation and Extinction (ClaSSE)-like models, our findings could also
be easily transferred to the macroevolution domain.
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