OmniBioTwin: A System-of-Twinned-Systems Framework for Health Digital Twins

This paper presents a proof-of-concept digital twin framework for simulation-driven diabetes modeling using benchmark clinical data, synthetic temporal augmentation, and illustrative continuous glucose monitoring (CGM) analysis. Unlike traditional predictive models, the framework focuses on generating interpretable simulated trajectories rather than clinically validated outcomes. Evaluation is conducted using a public dataset combined with controlled synthetic scenarios to illustrate temporal behavior and intervention effects. Results illustrate the feasibility of integrating prediction with counterfactual simulation for decision-aware analysis. This work does not claim clinical readiness but provides a foundation for future research on simulation-driven digital twin systems in healthcare.

Despite the central role of sensor-derived measurements such as imaging traits and plasma biomarkers in biomedical research and clinical practice, existing generative models for disease prediction largely depend on event-level representations from hospital and registry data. Given the multi-factorial nature of human disease, the absence of explicit modeling of social determinants of health (SDoH), even in the limited form of ICD-coded proxies (chapters Z and V--Y in ICD-10), limits the capacity for personalized disease modeling and clinical decision support. To address this limitation, we propose a generative model with ICD-coded proxies of SDoH for \textit{in silico} modeling of disease reasoning, a conditioned latent diffusion framework that establishes the connection between multi-organ sensor data with tokenized healthcare events. Specifically, we introduce a novel geometric diffusion model to characterize the temporal evolution of complex data representation such as brain networks (region-to-region connectivity encoded in a graph), in parallel with diffusion models for tabular data from other organ systems. Together, we integrate the generative model with digitalized SDoH proxies (coined \modelname{}) for simulated intervention and reasoning of future disease trajectories. We conduct extensive experiments on the UK Biobank (UKB) dataset, which contains organ-specific imaging traits, including brain (44,834), heart (23,987), liver (28,722), and kidney (32,155), along with nearly 500k medical history sequences (age range: 25$\sim$89 years). Our \modelname{} achieves significant improvements over state-of-the-art human disease autoregressive models and imaging trait generative baselines.

Building a blockchain digital twin largely requires translating domain knowledge and specific system descriptions into a simulator architecture, calibrating its parameters against behavioral evidence, and validating the constructed twin. These steps are commonly performed through application-specific modeling efforts that can be difficult to reuse across systems and downstream decision problems. We consider automating this process through Spec2Twin-Chain, a framework that formulates blockchain digital-twin construction as a bi-level optimization problem. At the upper level, a large language model proposes and revises structurally admissible architectures using system specifications, behavioral evidence, and feedback from evaluated designs. At the lower level, a simulation-based optimizer calibrates the architecture-conditioned parameters under explicit objectives and guardrail constraints. The two levels iterate. The evaluated candidates at lower levels are retained in a global archive and used to guide subsequent proposals at upper levels. We conduct controlled experiments involving twin calibration, feedback-driven recovery, stress analysis, downstream policy optimization, and policy updating. The results demonstrate that the framework can construct behaviorally accurate twins, improve initial designs through iterative feedback, and reuse calibrated twins to support downstream decisions.