Lucas Böttcher

Mingtao Xia, Lucas Böttcher, Tom Chou

Efficient testing and vaccination protocols are critical aspects of epidemic management. To study the optimal allocation of limited testing and vaccination resources in a heterogeneous contact network of interacting susceptible, recovered, and infected individuals, we present a degree-based testing and vaccination model for which we use control-theoretic methods to derive optimal testing and vaccination policies. Within our framework, we find that optimal intervention policies first target high-degree nodes before shifting to lower-degree nodes in a time-dependent manner. Using such optimal policies, it is possible to delay outbreaks and reduce incidence rates to a greater extent than uniform and reinforcement-learning-based interventions, particularly on certain scale-free networks.

Lucas Böttcher, Thomas Asikis

Optimal control problems naturally arise in many scientific applications where one wishes to steer a dynamical system from a certain initial state $\mathbf{x}_0$ to a desired target state $\mathbf{x}^*$ in finite time $T$. Recent advances in deep learning and neural network-based optimization have contributed to the development of methods that can help solve control problems involving high-dimensional dynamical systems. In particular, the framework of neural ordinary differential equations (neural ODEs) provides an efficient means to iteratively approximate continuous time control functions associated with analytically intractable and computationally demanding control tasks. Although neural ODE controllers have shown great potential in solving complex control problems, the understanding of the effects of hyperparameters such as network structure and optimizers on learning performance is still very limited. Our work aims at addressing some of these knowledge gaps to conduct efficient hyperparameter optimization. To this end, we first analyze how truncated and non-truncated backpropagation through time affect runtime performance and the ability of neural networks to learn optimal control functions. Using analytical and numerical methods, we then study the role of parameter initializations, optimizers, and neural-network architecture. Finally, we connect our results to the ability of neural ODE controllers to implicitly regularize control energy.

Lucas Böttcher, Gregory Wheeler

Analyzing geometric properties of high-dimensional loss functions, such as local curvature and the existence of other optima around a certain point in loss space, can help provide a better understanding of the interplay between neural network structure, implementation attributes, and learning performance. In this work, we combine concepts from high-dimensional probability and differential geometry to study how curvature properties in lower-dimensional loss representations depend on those in the original loss space. We show that saddle points in the original space are rarely correctly identified as such in expected lower-dimensional representations if random projections are used. The principal curvature in the expected lower-dimensional representation is proportional to the mean curvature in the original loss space. Hence, the mean curvature in the original loss space determines if saddle points appear, on average, as either minima, maxima, or almost flat regions. We use the connection between expected curvature in random projections and mean curvature in the original space (i.e., the normalized Hessian trace) to compute Hutchinson-type trace estimates without calculating Hessian-vector products as in the original Hutchinson method. Because random projections are not suitable to correctly identify saddle information, we propose to study projections along dominant Hessian directions that are associated with the largest and smallest principal curvatures. We connect our findings to the ongoing debate on loss landscape flatness and generalizability. Finally, for different common image classifiers and a function approximator, we show and compare random and Hessian projections of loss landscapes with up to about $7\times 10^6$ parameters.

Luis L. Fonseca, Reinhard C. Laubenbacher, Lucas Böttcher

Ordinary differential equation models of biochemical reactions are often formulated as stoichiometric systems in which the dynamics arise from a collection of interacting processes. A central challenge is that the functional form of each process is rarely known a priori and may be difficult to infer from data. We propose biochemically informed neural ordinary differential equations (BINODEs), a neural-ODE framework that retains the stoichiometric structure of mechanistic models while representing individual processes by neural networks. In BINODEs, the outputs of neural network processes (NNPs) are mapped to state derivatives through a linear layer analogous to a stoichiometric matrix. This architecture allows biological side information, such as process-specific inputs, sign constraints, and monotonicity assumptions, to be built directly into the model. We characterize the approximation properties of NNPs for several standard biochemical rate laws and show that the proposed framework recovers both trajectories and process-level structure in Monod, Lotka--Volterra, pharmacokinetic, and ultradian endocrine models. These results suggest that BINODEs offer a useful compromise between mechanistic interpretability and data-driven flexibility for modeling partially known biochemical or biological dynamical systems.

Lucas Böttcher

Ensemble Kalman inversion (EKI) is a sequential Monte Carlo method used to solve inverse problems within a Bayesian framework. Unlike backpropagation, EKI is a gradient-free optimization method that only necessitates the evaluation of artificial neural networks in forward passes. In this study, we examine the effectiveness of EKI in training neural ordinary differential equations (neural ODEs) for system identification and control tasks. To apply EKI to optimal control problems, we formulate inverse problems that incorporate a Tikhonov-type regularization term. Our numerical results demonstrate that EKI is an efficient method for training neural ODEs in system identification and optimal control problems, with runtime and quality of solutions that are competitive with commonly used gradient-based optimizers.

Lucas Böttcher, Luis L. Fonseca, Reinhard C. Laubenbacher

The objective of personalized medicine is to tailor interventions to an individual patient's unique characteristics. A key technology for this purpose involves medical digital twins, computational models of human biology that can be personalized and dynamically updated to incorporate patient-specific data collected over time. Certain aspects of human biology, such as the immune system, are not easily captured with physics-based models, such as differential equations. Instead, they are often multi-scale, stochastic, and hybrid. This poses a challenge to existing model-based control and optimization approaches that cannot be readily applied to such models. Recent advances in automatic differentiation and neural-network control methods hold promise in addressing complex control problems. However, the application of these approaches to biomedical systems is still in its early stages. This work introduces dynamics-informed neural-network controllers as an alternative approach to control of medical digital twins. As a first use case for this method, the focus is on agent-based models, a versatile and increasingly common modeling platform in biomedicine. The effectiveness of the proposed neural-network control method is illustrated and benchmarked against other methods with two widely-used agent-based model types. The relevance of the method introduced here extends beyond medical digital twins to other complex dynamical systems.

Lucas Böttcher

Control problems frequently arise in scientific and industrial applications, where the objective is to steer a dynamical system from an initial state to a desired target state. Recent advances in deep learning and automatic differentiation have made applying these methods to control problems increasingly practical. In this paper, we examine the use of neural networks and modern machine-learning libraries to parameterize control inputs across discrete-time and continuous-time systems, as well as deterministic and stochastic dynamics. We highlight applications in multiple domains, including biology, engineering, physics, and medicine. For continuous-time dynamical systems, neural ordinary differential equations (neural ODEs) offer a useful approach to parameterizing control inputs. For discrete-time systems, we show how custom control-input parameterizations can be implemented and optimized using automatic-differentiation methods. Overall, the methods presented provide practical solutions for control tasks that are computationally demanding or analytically intractable, making them valuable for complex real-world applications.

Yurun Ge, Lucas Böttcher, Tom Chou et al.

How to allocate limited resources to projects that will yield the greatest long-term benefits is a problem that often arises in decision-making under uncertainty. For example, organizations may need to evaluate and select innovation projects with risky returns. Similarly, when allocating resources to research projects, funding agencies are tasked with identifying the most promising proposals based on idiosyncratic criteria. Finally, in participatory budgeting, a local community may need to select a subset of public projects to fund. Regardless of context, agents must estimate the uncertain values of a potentially large number of projects. Developing parsimonious methods to compare these projects, and aggregating agent evaluations so that the overall benefit is maximized, are critical in assembling the best project portfolio. Unlike in standard sorting algorithms, evaluating projects on the basis of uncertain long-term benefits introduces additional complexities. We propose comparison rules based on Quicksort and the Bradley--Terry model, which connects rankings to pairwise "win" probabilities. In our model, each agent determines win probabilities of a pair of projects based on his or her specific evaluation of the projects' long-term benefit. The win probabilities are then appropriately aggregated and used to rank projects. Several of the methods we propose perform better than the two most effective aggregation methods currently available. Additionally, our methods can be combined with sampling techniques to significantly reduce the number of pairwise comparisons. We also discuss how the Bradley--Terry portfolio selection approach can be implemented in practice.

Lucas Böttcher, Gregory Wheeler

The field of neuroscience and the development of artificial neural networks (ANNs) have mutually influenced each other, drawing from and contributing to many concepts initially developed in statistical mechanics. Notably, Hopfield networks and Boltzmann machines are versions of the Ising model, a model extensively studied in statistical mechanics for over a century. In the first part of this chapter, we provide an overview of the principles, models, and applications of ANNs, highlighting their connections to statistical mechanics and statistical learning theory. Artificial neural networks can be seen as high-dimensional mathematical functions, and understanding the geometric properties of their loss landscapes (i.e., the high-dimensional space on which one wishes to find extrema or saddles) can provide valuable insights into their optimization behavior, generalization abilities, and overall performance. Visualizing these functions can help us design better optimization methods and improve their generalization abilities. Thus, the second part of this chapter focuses on quantifying geometric properties and visualizing loss functions associated with deep ANNs.

Mingtao Xia, Lucas Böttcher, Tom Chou

Solving analytically intractable partial differential equations (PDEs) that involve at least one variable defined on an unbounded domain arises in numerous physical applications. Accurately solving unbounded domain PDEs requires efficient numerical methods that can resolve the dependence of the PDE on the unbounded variable over at least several orders of magnitude. We propose a solution to such problems by combining two classes of numerical methods: (i) adaptive spectral methods and (ii) physics-informed neural networks (PINNs). The numerical approach that we develop takes advantage of the ability of physics-informed neural networks to easily implement high-order numerical schemes to efficiently solve PDEs and extrapolate numerical solutions at any point in space and time. We then show how recently introduced adaptive techniques for spectral methods can be integrated into PINN-based PDE solvers to obtain numerical solutions of unbounded domain problems that cannot be efficiently approximated by standard PINNs. Through a number of examples, we demonstrate the advantages of the proposed spectrally adapted PINNs in solving PDEs and estimating model parameters from noisy observations in unbounded domains.

Lucas Böttcher, Thomas Asikis, Ioannis Fragkos

A key challenge in inventory management is to identify policies that optimally replenish inventory from multiple suppliers. To solve such optimization problems, inventory managers need to decide what quantities to order from each supplier, given the net inventory and outstanding orders, so that the expected backlogging, holding, and sourcing costs are jointly minimized. Inventory management problems have been studied extensively for over 60 years, and yet even basic dual-sourcing problems, in which orders from an expensive supplier arrive faster than orders from a regular supplier, remain intractable in their general form. In addition, there is an emerging need to develop proactive, scalable optimization algorithms that can adjust their recommendations to dynamic demand shifts in a timely fashion. In this work, we approach dual sourcing from a neural network--based optimization lens and incorporate information on inventory dynamics and its replenishment (i.e., control) policies into the design of recurrent neural networks. We show that the proposed neural network controllers (NNCs) are able to learn near-optimal policies of commonly used instances within a few minutes of CPU time on a regular personal computer. To demonstrate the versatility of NNCs, we also show that they can control inventory dynamics with empirical, non-stationary demand distributions that are challenging to tackle effectively using alternative, state-of-the-art approaches. Our work shows that high-quality solutions of complex inventory management problems with non-stationary demand can be obtained with deep neural-network optimization approaches that directly account for inventory dynamics in their optimization process. As such, our research opens up new ways of efficiently managing complex, high-dimensional inventory dynamics.

Lucas Böttcher, Nino Antulov-Fantulin, Thomas Asikis

Although optimal control problems of dynamical systems can be formulated within the framework of variational calculus, their solution for complex systems is often analytically and computationally intractable. In this Letter we present a versatile neural ordinary-differential-equation control (NODEC) framework with implicit energy regularization and use it to obtain neural-network-generated control signals that can steer dynamical systems towards a desired target state within a predefined amount of time. We demonstrate the ability of NODEC to learn control signals that closely resemble those found by corresponding optimal control frameworks in terms of control energy and deviation from the desired target state. Our results suggest that NODEC is capable to solve a wide range of control and optimization problems, including those that are analytically intractable.

Thomas Asikis, Lucas Böttcher, Nino Antulov-Fantulin

We study the ability of neural networks to calculate feedback control signals that steer trajectories of continuous time non-linear dynamical systems on graphs, which we represent with neural ordinary differential equations (neural ODEs). To do so, we present a neural-ODE control (NODEC) framework and find that it can learn feedback control signals that drive graph dynamical systems into desired target states. While we use loss functions that do not constrain the control energy, our results show, in accordance with related work, that NODEC produces low energy control signals. Finally, we evaluate the performance and versatility of NODEC against well-known feedback controllers and deep reinforcement learning. We use NODEC to generate feedback controls for systems of more than one thousand coupled, non-linear ODEs that represent epidemic processes and coupled oscillators.

Francesco D'Angelo, Lucas Böttcher

Recent advances in deep learning and neural networks have led to an increased interest in the application of generative models in statistical and condensed matter physics. In particular, restricted Boltzmann machines (RBMs) and variational autoencoders (VAEs) as specific classes of neural networks have been successfully applied in the context of physical feature extraction and representation learning. Despite these successes, however, there is only limited understanding of their representational properties and limitations. To better understand the representational characteristics of RBMs and VAEs, we study their ability to capture physical features of the Ising model at different temperatures. This approach allows us to quantitatively assess learned representations by comparing sample features with corresponding theoretical predictions. Our results suggest that the considered RBMs and convolutional VAEs are able to capture the temperature dependence of magnetization, energy, and spin-spin correlations. The samples generated by RBMs are more evenly distributed across temperature than those generated by VAEs. We also find that convolutional layers in VAEs are important to model spin correlations whereas RBMs achieve similar or even better performances without convolutional filters.