Marc A. Suchard

Tianyu Xie, Frederick A. Matsen, Marc A. Suchard et al. · pku

Reconstructing the evolutionary history relating a collection of molecular sequences is the main subject of modern Bayesian phylogenetic inference. However, the commonly used Markov chain Monte Carlo methods can be inefficient due to the complicated space of phylogenetic trees, especially when the number of sequences is large. An alternative approach is variational Bayesian phylogenetic inference (VBPI) which transforms the inference problem into an optimization problem. While effective, the default diagonal lognormal approximation for the branch lengths of the tree used in VBPI is often insufficient to capture the complexity of the exact posterior. In this work, we propose a more flexible family of branch length variational posteriors based on semi-implicit hierarchical distributions using graph neural networks. We show that this semi-implicit construction emits straightforward permutation equivariant distributions, and therefore can handle the non-Euclidean branch length space across different tree topologies with ease. To deal with the intractable marginal probability of semi-implicit variational distributions, we develop several alternative lower bounds for stochastic optimization. We demonstrate the effectiveness of our proposed method over baseline methods on benchmark data examples, in terms of both marginal likelihood estimation and branch length posterior approximation.

Akihiko Nishimura, Marc A. Suchard

In a modern observational study based on healthcare databases, the number of observations and of predictors typically range in the order of $10^5$ ~ $10^6$ and of $10^4$ ~ $10^5$. Despite the large sample size, data rarely provide sufficient information to reliably estimate such a large number of parameters. Sparse regression techniques provide potential solutions, one notable approach being the Bayesian methods based on shrinkage priors. In the "large n & large p" setting, however, posterior computation encounters a major bottleneck at repeated sampling from a high-dimensional Gaussian distribution, whose precision matrix $Φ$ is expensive to compute and factorize. In this article, we present a novel algorithm to speed up this bottleneck based on the following observation: we can cheaply generate a random vector $b$ such that the solution to the linear system $Φβ= b$ has the desired Gaussian distribution. We can then solve the linear system by the conjugate gradient (CG) algorithm through matrix-vector multiplications by $Φ$; this involves no explicit factorization or calculation of $Φ$ itself. Rapid convergence of CG in this context is guaranteed by the theory of prior-preconditioning we develop. We apply our algorithm to a clinically relevant large-scale observational study with n = 72,489 patients and p = 22,175 clinical covariates, designed to assess the relative risk of adverse events from two alternative blood anti-coagulants. Our algorithm demonstrates an order of magnitude speed-up in posterior inference, in our case cutting the computation time from two weeks to less than a day.