Artificial-intelligence-driven Innovations in Mechanistic Computational Modeling and Digital Twins for Biomedical Applications

Abstract

Understanding of complex biological systems remains a significant challenge due to their high dimensionality, nonlinearity, and context-specific behavior. Artificial intelligence (AI) and mechanistic modeling are becoming essential tools for studying such complex systems. Mechanistic modeling can facilitate the construction of simulatable models that are interpretable but often struggle with scalability and parameters estimation. AI can integrate multi-omics data to create predictive models, but it lacks interpretability. The gap between these two modeling methods limits our ability to develop comprehensive and predictive models for biomedical applications. This article reviews the most recent advancements in the integration of AI and mechanistic modeling to fill this gap. Recently, with omics availability, AI has led to new discoveries in mechanistic computational modeling. The mechanistic models can also help in getting insight into the mechanism for prediction made by AI models. This integration is helpful in modeling complex systems, estimating the parameters that are hard to capture in experiments, and creating surrogate models to reduce computational costs because of expensive mechanistic model simulations. This article focuses on advancements in mechanistic computational models and AI models and their integration for scientific discoveries in biology, pharmacology, drug discovery and diseases. The mechanistic models with AI integration can facilitate biological discoveries to advance our understanding of disease mechanisms, drug development, and personalized medicine. The article also highlights the role of AI and mechanistic model integration in the development of more advanced models in the biomedical domain, such as medical digital twins and virtual patients for pharmacological discoveries.

Keywords: artificial intelligence; biomedicine; mechanistic modeling; medical digital twins; systems biology.