Adelinde M. Uhrmacher

Justin N. Kreikemeyer, Miłosz Jankowski, Pia Wilsdorf et al.

Formal languages are an integral part of modeling and simulation. They allow the distillation of knowledge into concise simulation models amenable to automatic execution, interpretation, and analysis. However, the arguably most humanly accessible means of expressing models is through natural language, which is not easily interpretable by computers. Here, we evaluate how a Large Language Model (LLM) might be used for formalizing natural language into simulation models. Existing studies only explored using very large LLMs, like the commercial GPT models, without fine-tuning model weights. To close this gap, we show how an open-weights, 7B-parameter Mistral model can be fine-tuned to translate natural language descriptions to reaction network models in a domain-specific language, offering a self-hostable, compute-efficient, and memory efficient alternative. To this end, we develop a synthetic data generator to serve as the basis for fine-tuning and evaluation. Our quantitative evaluation shows that our fine-tuned Mistral model can recover the ground truth simulation model in up to 84.5% of cases. In addition, our small-scale user study demonstrates the model's practical potential for one-time generation as well as interactive modeling in various domains. While promising, in its current form, the fine-tuned small LLM cannot catch up with large LLMs. We conclude that higher-quality training data are required, and expect future small and open-source LLMs to offer new opportunities.

Kevin Burrage, Pamela M. Burrage, Justin N. Kreikemeyer et al.

In this paper, we adapt a two-species agent-based cancer model that describes the interaction between cancer cells and healthy cells on a uniform grid to include the interaction with a third species -- namely immune cells. We run six different scenarios to explore the competition between cancer and immune cells and the initial concentration of the immune cells on cancer dynamics. We then use coupled equation learning to construct a population-based reaction model for each scenario. We show how they can be unified into a single surrogate population-based reaction model, whose underlying three coupled ordinary differential equations are much easier to analyse than the original agent-based model. As an example, by finding the single steady state of the cancer concentration, we are able to find a linear relationship between this concentration and the initial concentration of the immune cells. This then enables us to estimate suitable values for the competition and initial concentration to reduce the cancer substantially without performing additional complex and expensive simulations from an agent-based stochastic model.

Justin N. Kreikemeyer, Philipp Andelfinger, Adelinde M. Uhrmacher

Increasing effort is put into the development of methods for learning mechanistic models from data. This task entails not only the accurate estimation of parameters but also a suitable model structure. Recent work on the discovery of dynamical systems formulates this problem as a linear equation system. Here, we explore several simulation-based optimization approaches, which allow much greater freedom in the objective formulation and weaker conditions on the available data. We show that even for relatively small stochastic population models, simultaneous estimation of parameters and structure poses major challenges for optimization procedures. Particularly, we investigate the application of the local stochastic gradient descent method, commonly used for training machine learning models. We demonstrate accurate estimation of models but find that enforcing the inference of parsimonious, interpretable models drastically increases the difficulty. We give an outlook on how this challenge can be overcome.

Anja Wolpers, Johannes Ponge, Adelinde M. Uhrmacher

Non-pharmaceutical interventions (NPIs) are commonly used tools for controlling infectious disease transmission when pharmaceutical options are unavailable. Yet, identifying effective interventions that minimize societal disruption remains challenging. Agent-based simulation is a popular tool for analyzing the impact of possible interventions in epidemiology. However, automatically optimizing NPIs using agent-based simulations poses a complex problem because, in agent-based epidemiological models, interventions can target individuals based on multiple attributes, affect hierarchical group structures (e.g., schools, workplaces, and families), and be combined arbitrarily, resulting in a very large or even infinite search space. We aim to support decision-makers with our Agent-based Infectious Disease Intervention Optimization System (ADIOS) that optimizes NPIs for infectious disease simulations using Grammar-Guided Genetic Programming (GGGP). The core of ADIOS is a domain-specific language for expressing NPIs in agent-based simulations that structures the intervention search space through a context-free grammar. To make optimization more efficient, the search space can be further reduced by defining constraints that prevent the generation of semantically invalid intervention patterns. Using this constrained language and an interface that enables coupling with agent-based simulations, ADIOS adopts the GGGP approach for simulation-based optimization. Using the German Epidemic Micro-Simulation System (GEMS) as a case study, we demonstrate the potential of our approach to generate optimal interventions for realistic epidemiological models