Trend Filtered Mixture of Experts for Automated Gating of High-Frequency Flow Cytometry Data

Ocean microbes are critical to both ocean ecosystems and the global climate. Flow cytometry, which measures cell optical properties in fluid samples, is routinely used in oceanographic research. Despite decades of accumulated data, identifying key microbial populations (a process known as ``gating'') remains a significant analytical challenge. To address this, we focus on gating multidimensional, high-frequency flow cytometry data collected {\it continuously} on board oceanographic research vessels, capturing time- and space-wise variations in the dynamic ocean. Our paper proposes a novel mixture-of-experts model in which both the gating function and the experts are given by trend filtering. The model leverages two key assumptions: (1) Each snapshot of flow cytometry data is a mixture of multivariate Gaussians and (2) the parameters of these Gaussians vary smoothly over time. Our method uses regularization and a constraint to ensure smoothness and that cluster means match biologically distinct microbe types. We demonstrate, using flow cytometry data from the North Pacific Ocean, that our proposed model accurately matches human-annotated gating and corrects significant errors.

Modeling Cell Populations Measured By Flow Cytometry With Covariates Using Sparse Mixture of Regressions

The ocean is filled with microscopic microalgae called phytoplankton, which together are responsible for as much photosynthesis as all plants on land combined. Our ability to predict their response to the warming ocean relies on understanding how the dynamics of phytoplankton populations is influenced by changes in environmental conditions. One powerful technique to study the dynamics of phytoplankton is flow cytometry, which measures the optical properties of thousands of individual cells per second. Today, oceanographers are able to collect flow cytometry data in real-time onboard a moving ship, providing them with fine-scale resolution of the distribution of phytoplankton across thousands of kilometers. One of the current challenges is to understand how these small and large scale variations relate to environmental conditions, such as nutrient availability, temperature, light and ocean currents. In this paper, we propose a novel sparse mixture of multivariate regressions model to estimate the time-varying phytoplankton subpopulations while simultaneously identifying the specific environmental covariates that are predictive of the observed changes to these subpopulations. We demonstrate the usefulness and interpretability of the approach using both synthetic data and real observations collected on an oceanographic cruise conducted in the north-east Pacific in the spring of 2017.