Online tree expansion could help solve the problem of scalability in Bayesian phylogenetics.

Bayesian phylogenetics is now facing a critical point. Over the last 20 years, Bayesian methods have reshaped phylogenetic inference and gained widespread popularity due to their high accuracy, the ability to quantify the uncertainty of inferences and the possibility of accommodating multiple aspects of evolutionary processes in the models that are used. Unfortunately, Bayesian methods are computationally expensive, and typical applications involve at most a few hundred sequences. This is problematic in the age of rapidly expanding genomic data and increasing scope of evolutionary analyses, forcing researchers to resort to less accurate but faster methods, such as maximum parsimony and maximum likelihood. Does this spell doom for Bayesian methods? Not necessarily. Here, we discuss some recently proposed approaches that could help scale up Bayesian analyses of evolutionary problems considerably. We focus on two particular aspects: online phylogenetics, where new data sequences are added to existing analyses, and alternatives to Markov chain Monte Carlo (MCMC) for scalable Bayesian inference. We identify 5 specific challenges and discuss how they might be overcome. We believe that online phylogenetic approaches and Sequential Monte Carlo hold great promise and could potentially speed up tree inference by orders of magnitude. We call for collaborative efforts to speed up the development of methods for real-time tree expansion through online phylogenetics.

Universal probabilistic programming offers a powerful approach to statistical phylogenetics.

Statistical phylogenetic analysis currently relies on complex, dedicated software packages, making it difficult for evolutionary biologists to explore new models and inference strategies. Recent years have seen more generic solutions based on probabilistic graphical models, but this formalism can only partly express phylogenetic problems. Here, we show that universal probabilistic programming languages (PPLs) solve the expressivity problem, while still supporting automated generation of efficient inference algorithms. To prove the latter point, we develop automated generation of sequential Monte Carlo (SMC) algorithms for PPL descriptions of arbitrary biological diversification (birth-death) models. SMC is a new inference strategy for these problems, supporting both parameter inference and efficient estimation of Bayes factors that are used in model testing. We take advantage of this in automatically generating SMC algorithms for several recent diversification models that have been difficult or impossible to tackle previously. Finally, applying these algorithms to 40 bird phylogenies, we show that models with slowing diversification, constant turnover and many small shifts generally explain the data best. Our work opens up several related problem domains to PPL approaches, and shows that few hurdles remain before these techniques can be effectively applied to the full range of phylogenetic models.