Gathering observational data for medical decision-making often involves uncertainties arising from both type I (false positive) and type II (false negative) errors. In this work, we develop a statistical model to study how medical decision-making can be improved by aggregating results from repeated diagnostic and screening tests. Our approach is relevant to not only clinical settings such as medical imaging, but also to public health, as highlighted by the need for rapid, cost-effective testing methods during the SARS-CoV-2 pandemic. Our model enables the development of testing protocols with an arbitrary number of tests, which can be customized to meet requirements for type I and type II errors. This allows us to adjust sensitivity and specificity according to application-specific needs. Additionally, we derive generalized Rogan-Gladen estimates of disease prevalence that account for an arbitrary number of tests with potentially different type I and type II errors. We also provide the corresponding uncertainty quantification.

[This corrects the article DOI: 10.1371/journal.pcbi.1012749.].

This paper describes and validates an algorithm to solve optimal control problems for agent-based models (ABMs). For a given ABM and a given optimal control problem, the algorithm derives a surrogate model, typically lower-dimensional, in the form of a system of ordinary differential equations (ODEs), solves the control problem for the surrogate model, and then transfers the solution back to the original ABM. It applies to quite general ABMs and offers several options for the ODE structure, depending on what information about the ABM is to be used. There is a broad range of applications for such an algorithm, since ABMs are used widely in the life sciences, such as ecology, epidemiology, and biomedicine and healthcare, areas where optimal control is an important purpose for modeling, such as for medical digital twin technology.

Proper regulation of cell signaling and gene expression is crucial for maintaining cellular function, development, and adaptation to environmental changes. Reaction dynamics in cell populations is often noisy because of (i) inherent stochasticity of intracellular biochemical reactions ("intrinsic noise") and (ii) heterogeneity of cellular states across different cells that are influenced by external factors ("extrinsic noise"). In this work, we introduce an extrinsic-noise-driven neural stochastic differential equation (END-nSDE) framework that utilizes the Wasserstein distance to accurately reconstruct SDEs from stochastic trajectories measured across a heterogeneous population of cells (extrinsic noise). We demonstrate the effectiveness of our approach using both simulated and experimental data from three different systems in cell biology: (i) circadian rhythms, (ii) RPA-DNA binding dynamics, and (iii) NF[Formula: see text]B signaling processes. Our END-nSDE reconstruction method can model how cellular heterogeneity (extrinsic noise) modulates reaction dynamics in the presence of intrinsic noise. It also outperforms existing time-series analysis methods such as recurrent neural networks (RNNs) and long short-term memory networks (LSTMs). By inferring cellular heterogeneities from data, our END-nSDE reconstruction method can reproduce noisy dynamics observed in experiments. In summary, the reconstruction method we propose offers a useful surrogate modeling approach for complex biophysical processes, where high-fidelity mechanistic models may be impractical.

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 more than 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, nonstationary 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 nonstationary 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. History: Accepted by Ram Ramesh, Area Editor for Data Science & Machine Learning. Funding: This work was supported by Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (NCCR Automation) [Grant P2EZP2 191888] and the Army Research Office [Grant W911NF-23-1-0129]. Supplemental Material: The software that supports the findings of this study is available within the paper and its Supplemental Information ( https://pubsonline.informs.org/doi/suppl/10.1287/ijoc.2022.0136 ) as well as from the IJOC GitHub software repository ( https://github.com/INFORMSJoC/2022.0136 ). The complete IJOC Software and Data Repository is available at https://informsjoc.github.io/ .

Testing, contact tracing, and isolation (TTI) is an epidemic management and control approach that is difficult to implement at scale because it relies on manual tracing of contacts. Exposure notification apps have been developed to digitally scale up TTI by harnessing contact data obtained from mobile devices; however, exposure notification apps provide users only with limited binary information when they have been directly exposed to a known infection source. Here we demonstrate a scalable improvement to TTI and exposure notification apps that uses data assimilation (DA) on a contact network. Network DA exploits diverse sources of health data together with the proximity data from mobile devices that exposure notification apps rely upon. It provides users with continuously assessed individual risks of exposure and infection, which can form the basis for targeting individual contact interventions. Simulations of the early COVID-19 epidemic in New York City are used to establish proof-of-concept. In the simulations, network DA identifies up to a factor 2 more infections than contact tracing when both harness the same contact data and diagnostic test data. This remains true even when only a relatively small fraction of the population uses network DA. When a sufficiently large fraction of the population (≳ 75%) uses network DA and complies with individual contact interventions, targeting contact interventions with network DA reduces deaths by up to a factor 4 relative to TTI. Network DA can be implemented by expanding the computational backend of existing exposure notification apps, thus greatly enhancing their capabilities. Implemented at scale, it has the potential to precisely and effectively control future epidemics while minimizing economic disruption.