Building Digital Twins of Different Human Organs for Personalized Healthcare

Digital twins are virtual replicas of physical entities and are poised to transform personalized medicine through the real-time simulation and prediction of human physiology. Translating this paradigm from engineering to biomedicine requires overcoming profound challenges, including anatomical variability, multi-scale biological processes, and the integration of multi-physics phenomena. This survey systematically reviews methodologies for building digital twins of human organs, structured around a pipeline decoupled into anatomical twinning (capturing patient-specific geometry and structure) and functional twinning (simulating multi-scale physiology from cellular to organ-level function). We categorize approaches both by organ-specific properties and by technical paradigm, with particular emphasis on multi-scale and multi-physics integration. A key focus is the role of artificial intelligence (AI), especially physics-informed AI, in enhancing model fidelity, scalability, and personalization. Furthermore, we discuss the critical challenges of clinical validation and translational pathways. This study not only charts a roadmap for overcoming current bottlenecks in single-organ twins but also outlines the promising, albeit ambitious, future of interconnected multi-organ digital twins for whole-body precision healthcare.

Predicting Long-Term Allograft Survival in Liver Transplant Recipients

Liver allograft failure occurs in approximately 20% of liver transplant recipients within five years post-transplant, leading to mortality or the need for retransplantation. Providing an accurate and interpretable model for individualized risk estimation of graft failure is essential for improving post-transplant care. To this end, we introduce the Model for Allograft Survival (MAS), a simple linear risk score that outperforms other advanced survival models. Using longitudinal patient follow-up data from the United States (U.S.), we develop our models on 82,959 liver transplant recipients and conduct multi-site evaluations on 11 regions. Additionally, by testing on a separate non-U.S. cohort, we explore the out-of-distribution generalization performance of various models without additional fine-tuning, a crucial property for clinical deployment. We find that the most complex models are also the ones most vulnerable to distribution shifts despite achieving the best in-distribution performance. Our findings not only provide a strong risk score for predicting long-term graft failure but also suggest that the routine machine learning pipeline with only in-distribution held-out validation could create harmful consequences for patients at deployment.

Prediction of New Onset Diabetes after Liver Transplant

25% of people who received a liver transplant will go on to develop diabetes within the next 5 years. These thousands of individuals are at 2-fold higher risk of cardiovascular events, graft loss, infections, as well as lower long-term survival. This is partly due to the medication used during and/or after transplant that significantly impacts metabolic balance. To assess which medication best suits the patient's condition, clinicians need an accurate estimate of diabetes risk. Both patient's historical data and observations at the current visit are informative in predicting whether the patient will develop diabetes within the following year. In this work we compared a variety of time-to-event prediction models as well as classifiers predicting the likelihood of the event within a year from the current checkup. We are particularly interested in comparing two types of models: 1) standard time-to-event predictors where the historical measurements are merely concatenated, 2) incorporating Deep Markov Model to first obtain low-dimensional embedding of historical data and then using this embedding as an additional input into the model. We compared a variety of algorithms including standard and regularized Cox proportional-hazards model (CPH), mixed effect random forests, survival-forests and Weibull Time-To-Event Recurrent Neural Network (WTTE-RNN). The results show that although all methods' performances varied from year to year and there was no clear winner across all the time points, regularized CPH model that used 1 to 3 years of historical visits data on average achieved a high, clinically relevant Concordance Index of .863. We thus recommend this model for further prospective clinical validation and hopefully, an eventual use in the clinic to improve clinicians' ability to personalize post-operative care and reduce the incidence of new-onset diabetes post liver transplant.