From Noise to Signal: Unveiling Treatment Effects from Digital Health Data through Pharmacology-Informed Neural-SDE

Digital health technologies (DHT), such as wearable devices, provide personalized, continuous, and real-time monitoring of patient. These technologies are contributing to the development of novel therapies and personalized medicine. Gaining insight from these technologies requires appropriate modeling techniques to capture clinically-relevant changes in disease state. The data generated from these devices is characterized by being stochastic in nature, may have missing elements, and exhibits considerable inter-individual variability - thereby making it difficult to analyze using traditional longitudinal modeling techniques. We present a novel pharmacology-informed neural stochastic differential equation (SDE) model capable of addressing these challenges. Using synthetic data, we demonstrate that our approach is effective in identifying treatment effects and learning causal relationships from stochastic data, thereby enabling counterfactual simulation.

Tipping Points of Evolving Epidemiological Networks: Machine Learning-Assisted, Data-Driven Effective Modeling

We study the tipping point collective dynamics of an adaptive susceptible-infected-susceptible (SIS) epidemiological network in a data-driven, machine learning-assisted manner. We identify a parameter-dependent effective stochastic differential equation (eSDE) in terms of physically meaningful coarse mean-field variables through a deep-learning ResNet architecture inspired by numerical stochastic integrators. We construct an approximate effective bifurcation diagram based on the identified drift term of the eSDE and contrast it with the mean-field SIS model bifurcation diagram. We observe a subcritical Hopf bifurcation in the evolving network's effective SIS dynamics, that causes the tipping point behavior; this takes the form of large amplitude collective oscillations that spontaneously -- yet rarely -- arise from the neighborhood of a (noisy) stationary state. We study the statistics of these rare events both through repeated brute force simulations and by using established mathematical/computational tools exploiting the right-hand-side of the identified SDE. We demonstrate that such a collective SDE can also be identified (and the rare events computations also performed) in terms of data-driven coarse observables, obtained here via manifold learning techniques, in particular Diffusion Maps. The workflow of our study is straightforwardly applicable to other complex dynamics problems exhibiting tipping point dynamics.

Machine Learning for the identification of phase-transitions in interacting agent-based systems

Deriving closed-form, analytical expressions for reduced-order models, and judiciously choosing the closures leading to them, has long been the strategy of choice for studying phase- and noise-induced transitions for agent-based models (ABMs). In this paper, we propose a data-driven framework that pinpoints phase transitions for an ABM in its mean-field limit, using a smaller number of variables than traditional closed-form models. To this end, we use the manifold learning algorithm Diffusion Maps to identify a parsimonious set of data-driven latent variables, and show that they are in one-to-one correspondence with the expected theoretical order parameter of the ABM. We then utilize a deep learning framework to obtain a conformal reparametrization of the data-driven coordinates that facilitates, in our example, the identification of a single parameter-dependent ODE in these coordinates. We identify this ODE through a residual neural network inspired by a numerical integration scheme (forward Euler). We then use the identified ODE -- enabled through an odd symmetry transformation -- to construct the bifurcation diagram exhibiting the phase transition.

Nonlinear dimensionality reduction then and now: AIMs for dissipative PDEs in the ML era

This study presents a collection of purely data-driven workflows for constructing reduced-order models (ROMs) for distributed dynamical systems. The ROMs we focus on, are data-assisted models inspired by, and templated upon, the theory of Approximate Inertial Manifolds (AIMs); the particular motivation is the so-called post-processing Galerkin method of Garcia-Archilla, Novo and Titi. Its applicability can be extended: the need for accurate truncated Galerkin projections and for deriving closed-formed corrections can be circumvented using machine learning tools. When the right latent variables are not a priori known, we illustrate how autoencoders as well as Diffusion Maps (a manifold learning scheme) can be used to discover good sets of latent variables and test their explainability. The proposed methodology can express the ROMs in terms of (a) theoretical (Fourier coefficients), (b) linear data-driven (POD modes) and/or (c) nonlinear data-driven (Diffusion Maps) coordinates. Both Black-Box and (theoretically-informed and data-corrected) Gray-Box models are described; the necessity for the latter arises when truncated Galerkin projections are so inaccurate as to not be amenable to post-processing. We use the Chafee-Infante reaction-diffusion and the Kuramoto-Sivashinsky dissipative partial differential equations to illustrate and successfully test the overall framework.

Tasks Makyth Models: Machine Learning Assisted Surrogates for Tipping Points

We present a machine learning (ML)-assisted framework bridging manifold learning, neural networks, Gaussian processes, and Equation-Free multiscale modeling, for (a) detecting tipping points in the emergent behavior of complex systems, and (b) characterizing probabilities of rare events (here, catastrophic shifts) near them. Our illustrative example is an event-driven, stochastic agent-based model (ABM) describing the mimetic behavior of traders in a simple financial market. Given high-dimensional spatiotemporal data -- generated by the stochastic ABM -- we construct reduced-order models for the emergent dynamics at different scales: (a) mesoscopic Integro-Partial Differential Equations (IPDEs); and (b) mean-field-type Stochastic Differential Equations (SDEs) embedded in a low-dimensional latent space, targeted to the neighborhood of the tipping point. We contrast the uses of the different models and the effort involved in learning them.

Learning Effective SDEs from Brownian Dynamics Simulations of Colloidal Particles

We construct a reduced, data-driven, parameter dependent effective Stochastic Differential Equation (eSDE) for electric-field mediated colloidal crystallization using data obtained from Brownian Dynamics Simulations. We use Diffusion Maps (a manifold learning algorithm) to identify a set of useful latent observables. In this latent space we identify an eSDE using a deep learning architecture inspired by numerical stochastic integrators and compare it with the traditional Kramers-Moyal expansion estimation. We show that the obtained variables and the learned dynamics accurately encode the physics of the Brownian Dynamic Simulations. We further illustrate that our reduced model captures the dynamics of corresponding experimental data. Our dimension reduction/reduced model identification approach can be easily ported to a broad class of particle systems dynamics experiments/models.

Double Diffusion Maps and their Latent Harmonics for Scientific Computations in Latent Space

We introduce a data-driven approach to building reduced dynamical models through manifold learning; the reduced latent space is discovered using Diffusion Maps (a manifold learning technique) on time series data. A second round of Diffusion Maps on those latent coordinates allows the approximation of the reduced dynamical models. This second round enables mapping the latent space coordinates back to the full ambient space (what is called lifting); it also enables the approximation of full state functions of interest in terms of the reduced coordinates. In our work, we develop and test three different reduced numerical simulation methodologies, either through pre-tabulation in the latent space and integration on the fly or by going back and forth between the ambient space and the latent space. The data-driven latent space simulation results, based on the three different approaches, are validated through (a) the latent space observation of the full simulation through the Nystr\"om Extension formula, or through (b) lifting the reduced trajectory back to the full ambient space, via Latent Harmonics. Latent space modeling often involves additional regularization to favor certain properties of the space over others, and the mapping back to the ambient space is then constructed mostly independently from these properties; here, we use the same data-driven approach to construct the latent space and then map back to the ambient space.

On the Parameter Combinations That Matter and on Those That do Not

We present a data-driven approach to characterizing nonidentifiability of a model's parameters and illustrate it through dynamic kinetic models. By employing Diffusion Maps and their extensions, we discover the minimal combinations of parameters required to characterize the dynamic output behavior: a set of effective parameters for the model. Furthermore, we use Conformal Autoencoder Neural Networks, as well as a kernel-based Jointly Smooth Function technique, to disentangle the redundant parameter combinations that do not affect the output behavior from the ones that do. We discuss the interpretability of our data-driven effective parameters and demonstrate the utility of the approach both for behavior prediction and parameter estimation. In the latter task, it becomes important to describe level sets in parameter space that are consistent with a particular output behavior. We validate our approach on a model of multisite phosphorylation, where a reduced set of effective parameters, nonlinear combinations of the physical ones, has previously been established analytically.

Learning effective stochastic differential equations from microscopic simulations: combining stochastic numerics and deep learning

We identify effective stochastic differential equations (SDE) for coarse observables of fine-grained particle- or agent-based simulations; these SDE then provide coarse surrogate models of the fine scale dynamics. We approximate the drift and diffusivity functions in these effective SDE through neural networks, which can be thought of as effective stochastic ResNets. The loss function is inspired by, and embodies, the structure of established stochastic numerical integrators (here, Euler-Maruyama and Milstein); our approximations can thus benefit from error analysis of these underlying numerical schemes. They also lend themselves naturally to "physics-informed" gray-box identification when approximate coarse models, such as mean field equations, are available. Our approach does not require long trajectories, works on scattered snapshot data, and is designed to naturally handle different time steps per snapshot. We consider both the case where the coarse collective observables are known in advance, as well as the case where they must be found in a data-driven manner.

Initializing LSTM internal states via manifold learning

We present an approach, based on learning an intrinsic data manifold, for the initialization of the internal state values of LSTM recurrent neural networks, ensuring consistency with the initial observed input data. Exploiting the generalized synchronization concept, we argue that the converged, "mature" internal states constitute a function on this learned manifold. The dimension of this manifold then dictates the length of observed input time series data required for consistent initialization. We illustrate our approach through a partially observed chemical model system, where initializing the internal LSTM states in this fashion yields visibly improved performance. Finally, we show that learning this data manifold enables the transformation of partially observed dynamics into fully observed ones, facilitating alternative identification paths for nonlinear dynamical systems.