Reconstructing Kinetic Models for Dynamical Studies of Metabolism using Generative Adversarial Networks

Kinetic models of metabolism relate metabolic fluxes, metabolite concentrations and enzyme levels through mechanistic relations, rendering them essential for understanding, predicting and optimizing the behaviour of living organisms. However, due to the lack of kinetic data, traditional kinetic modelling often yields only a few or no kinetic models with desirable dynamical properties, making the analysis unreliable and computationally inefficient. We present REKINDLE (Reconstruction of Kinetic Models using Deep Learning), a deep-learning-based framework for efficiently generating kinetic models with dynamic properties matching the ones observed in cells. We showcase REKINDLE's capabilities to navigate through the physiological states of metabolism using small numbers of data with significantly lower computational requirements. The results show that data-driven neural networks assimilate implicit kinetic knowledge and structure of metabolic networks and generate kinetic models with tailored properties and statistical diversity. We anticipate that our framework will advance our understanding of metabolism and accelerate future research in biotechnology and health. Kinetic models of metabolism capture time-dependent behaviour of cellular states and provide valuable insights into cellular physiology, but, due to the lack of experimental data, traditional kinetic modelling can be unreliable and computationally inefficient. A generative framework based on deep learning called REKINDLE can efficiently parameterize large-scale kinetic models, enabling new opportunities to study cellular metabolic behaviour.

Automated summary

Kinetic models of metabolism play a crucial role in understanding cellular physiology, but traditional kinetic modeling methods are unreliable and computationally inefficient due to lack of experimental data. A deep learning framework called REKINDLE efficiently generates dynamic kinetic models that match observed cellular behavior, providing new opportunities for studying cellular metabolic behavior.