An important approach for scientific inquiry across many disciplines involves using observational time series data to understand the relationships between key variables to gain mechanistic insights into the underlying rules that govern the given system. In real systems, such as those found in ecology, the relationships between time series variables are generally not static; instead, these relationships are dynamical and change in a nonlinear or state-dependent manner. To further understand such systems, we investigate integrating methods that appropriately characterize these dynamics (i.e., methods that measure interactions as they change with time-varying system states) with visualization techniques that can help analyze the behavior of the system. Here, we focus on empirical dynamic modeling (EDM) as a state-of-the-art method that specifically identifies causal variables and measures changing state-dependent relationships between time series variables. Instead of using approaches centered on parametric equations, EDM is an equation-free approach that studies systems based on their dynamic attractors. We propose a visual analytics system to support the identification and mechanistic interpretation of system states using an EDM-constructed dynamic graph. This work, as detailed in four analysis tasks and demonstrated with a GUI, provides a novel synthesis of EDM and visualization techniques such as brush-link visualization and visual summarization to interpret dynamic graphs representing ecosystem dynamics. We applied our proposed system to ecological simulation data and real data from a marine mesocosm study as two key use cases. Our case studies show that our visual analytics tools support the identification and interpretation of the system state by the user, and enable us to discover both confirmatory and new findings in ecosystem dynamics. Overall, we demonstrated that our system can facilitate an understanding of how systems function beyond the intuitive analysis of high-dimensional information based on specific domain knowledge.

Empirical Dynamic Modeling (EDM) is a nonlinear time series causal inference framework. The latest implementation of EDM, cppEDM, has only been used for small datasets due to computational cost. With the growth of data collection capabilities, there is a great need to identify causal relationships in large datasets. We present mpEDM, a parallel distributed implementation of EDM optimized for modern GPU-centric supercomputers. We improve the original algorithm to reduce redundant computation and optimize the implementation to fully utilize hardware resources such as GPUs and SIMD units. As a use case, we run mpEDM on AI Bridging Cloud Infrastructure (ABCI) using datasets of an entire animal brain sampled at single neuron resolution to identify dynamical causation patterns across the brain. mpEDM is 1,530× faster than cppEDM and a dataset containing 101,729 neuron was analyzed in 199 seconds on 512 nodes. This is the largest EDM causal inference achieved to date.

BACKGROUND: Biochemical networks are often described through static or time-averaged measurements of the component macromolecules. Temporal variation in these components plays an important role in both describing the dynamical nature of the network as well as providing insights into causal mechanisms. Few methods exist, specifically for systems with many variables, for analyzing time series data to identify distinct temporal regimes and the corresponding time-varying causal networks and mechanisms. RESULTS: In this study, we use well-constructed temporal transcriptional measurements in a mammalian cell during a cell cycle, to identify dynamical networks and mechanisms describing the cell cycle. The methods we have used and developed in part deal with Granger causality, Vector Autoregression, Estimation Stability with Cross Validation and a nonparametric change point detection algorithm that enable estimating temporally evolving directed networks that provide a comprehensive picture of the crosstalk among different molecular components. We applied our approach to RNA-seq time-course data spanning nearly two cell cycles from Mouse Embryonic Fibroblast (MEF) primary cells. The change-point detection algorithm is able to extract precise information on the duration and timing of cell cycle phases. Using Least Absolute Shrinkage and Selection Operator (LASSO) and Estimation Stability with Cross Validation (ES-CV), we were able to, without any prior biological knowledge, extract information on the phase-specific causal interaction of cell cycle genes, as well as temporal interdependencies of biological mechanisms through a complete cell cycle. CONCLUSIONS: The temporal dependence of cellular components we provide in our model goes beyond what is known in the literature. Furthermore, our inference of dynamic interplay of multiple intracellular mechanisms and their temporal dependence on one another can be used to predict time-varying cellular responses, and provide insight on the design of precise experiments for modulating the regulation of the cell cycle.