Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America.
Department of Biostatistics, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, United States of America.
PLoS Comput Biol. 2023 Aug 28;19(8):e1011419. doi: 10.1371/journal.pcbi.1011419. eCollection 2023 Aug.
Inferring dependencies between mixed-type biological traits while accounting for evolutionary relationships between specimens is of great scientific interest yet remains infeasible when trait and specimen counts grow large. The state-of-the-art approach uses a phylogenetic multivariate probit model to accommodate binary and continuous traits via a latent variable framework, and utilizes an efficient bouncy particle sampler (BPS) to tackle the computational bottleneck-integrating many latent variables from a high-dimensional truncated normal distribution. This approach breaks down as the number of specimens grows and fails to reliably characterize conditional dependencies between traits. Here, we propose an inference pipeline for phylogenetic probit models that greatly outperforms BPS. The novelty lies in 1) a combination of the recent Zigzag Hamiltonian Monte Carlo (Zigzag-HMC) with linear-time gradient evaluations and 2) a joint sampling scheme for highly correlated latent variables and correlation matrix elements. In an application exploring HIV-1 evolution from 535 viruses, the inference requires joint sampling from an 11,235-dimensional truncated normal and a 24-dimensional covariance matrix. Our method yields a 5-fold speedup compared to BPS and makes it possible to learn partial correlations between candidate viral mutations and virulence. Computational speedup now enables us to tackle even larger problems: we study the evolution of influenza H1N1 glycosylations on around 900 viruses. For broader applicability, we extend the phylogenetic probit model to incorporate categorical traits, and demonstrate its use to study Aquilegia flower and pollinator co-evolution.
推断混合类型生物特征之间的依赖性,同时考虑标本之间的进化关系,这是一项具有重要科学意义的工作,但当特征和标本数量增加时,这种方法仍然不可行。目前的方法是使用一种基于系统发育的多元概率比模型,通过潜在变量框架来处理二分类和连续特征,并利用高效的弹跳粒子抽样器(BPS)来解决计算瓶颈——从高维截断正态分布中集成许多潜在变量。当标本数量增加时,这种方法会失效,并且无法可靠地描述特征之间的条件依赖性。在这里,我们提出了一种用于系统发育概率比模型的推断管道,该方法大大优于 BPS。其新颖之处在于:1)将最近的 Zigzag Hamiltonian Monte Carlo(Zigzag-HMC)与线性时间梯度评估相结合;2)用于高度相关的潜在变量和相关矩阵元素的联合抽样方案。在一个探索从 535 个病毒中进化而来的 HIV-1 的应用中,推断需要从一个 11235 维截断正态分布和一个 24 维协方差矩阵中进行联合抽样。与 BPS 相比,我们的方法提高了 5 倍的速度,并使得研究候选病毒突变与毒力之间的部分相关性成为可能。现在的计算速度加快了,我们甚至可以处理更大的问题:我们研究了大约 900 个病毒中的流感 H1N1 糖基化的进化。为了更广泛的适用性,我们将系统发育概率比模型扩展到包含分类特征,并演示了它在研究 Aquilegia 花和传粉者共同进化中的应用。