Abstract

Blood coagulation, which involves a group of complex biochemical reactions, is a crucial step in hemostasis to stop bleeding at the injury site of a blood vessel. Coagulation abnormalities, such as hypercoagulation and hypocoagulation, could either cause thrombosis or hemorrhage, resulting in severe clinical consequences. Mathematical models of blood coagulation have been widely used to improve the understanding of the pathophysiology of coagulation disorders, guide the design and testing of new anticoagulants or other therapeutic agents, and promote precision medicine. However, estimating the parameters in these coagulation models has been challenging as not all reaction rate constants and new parameters derived from model assumptions are measurable. Although various conventional methods have been employed for parameter estimation for coagulation models, the existing approaches have several shortcomings. Inspired by the physics-informed neural networks, we propose Coagulo-Net, which synergizes the strengths of deep neural networks with the mechanistic understanding of the blood coagulation processes to enhance the mathematical models of the blood coagulation cascade. We assess the performance of the Coagulo-Net using two existing coagulation models with different extents of complexity. Our simulation results illustrate that Coagulo-Net can efficiently infer the unknown model parameters and dynamics of species based on sparse measurement data and data contaminated with noise. In addition, we show that Coagulo-Net can process a mixture of synthetic and experimental data and refine the predictions of existing mathematical models of coagulation. These results demonstrate the promise of Coagulo-Net in enhancing current coagulation models and aiding the creation of novel models for physiological and pathological research. These results showcase the potential of Coagulo-Net to advance computational modeling in the study of blood coagulation, improving both research methodologies and the development of new therapies for treating patients with coagulation disorders.

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