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Digital Twin AI: Opportunities and Challenges from Large Language Models to World Models

arXiv:2601.01321v1 Announce Type: new Abstract: Digital twins, as precise digital representations of physical systems, have evolved from passive simulation tools into intelligent and autonomous entities through the integration of artificial intelligence technologies. This paper presents a unified four-stage framework that systematically characterizes AI integration across the digital twin lifecycle, spanning modeling, mirroring, intervention, and autonomous management. By synthesizing existing technologies and practices, we distill a unified four-stage framework that systematically characterizes how AI methodologies are embedded across the digital twin lifecycle: (1) modeling the physical twin through physics-based and physics-informed AI approaches, (2) mirroring the physical system into a digital twin with real-time synchronization, (3) intervening in the physical twin through predictive modeling, anomaly detection, and optimization strategies, and (4) achieving autonomous management through large language models, foundation models, and intelligent agents. We analyze the synergy between physics-based modeling and data-driven learning, highlighting the shift from traditional numerical solvers to physics-informed and foundation models for physical systems. Furthermore, we examine how generative AI technologies, including large language models and generative world models, transform digital twins into proactive and self-improving cognitive systems capable of reasoning, communication, and creative scenario generation. Through a cross-domain review spanning eleven application domains, including healthcare, aerospace, smart manufacturing, robotics, and smart cities, we identify common challenges related to scalability, explainability, and trustworthiness, and outline directions for responsible AI-driven digital twin systems.
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Wearable-informed generative digital avatars predict task-conditioned post-stroke locomotion

arXiv:2512.14329v2 Announce Type: replace-cross Abstract: Dynamic prediction of locomotor capacity after stroke could enable more individualized rehabilitation, yet current assessments largely provide static impairment scores and do not indicate whether patients can perform specific tasks such as slope walking or stair climbing. Here, we present a wearable-informed data-physics hybrid generative framework that reconstructs a stroke survivor's locomotor control from wearable inertial sensing and predicts task-conditioned post-stroke locomotion in new environments. From a single 20 m level-ground walking trial recorded by five IMUs, the framework personalizes a physics-based digital avatar using a healthy-motion prior and hybrid imitation learning, generating dynamically feasible, patient-specific movements for inclined walking and stair negotiation. Across 11 stroke inpatients, predicted postures reached 82.2% similarity for slopes and 69.9% for stairs, substantially exceeding a physics-only baseline. In a multicentre pilot randomized study (n = 21; 28 days), access to scenario-specific locomotion predictions to support task selection and difficulty titration was associated with larger gains in Fugl-Meyer lower-extremity scores than standard care (mean change 6.0 vs 3.7 points; $p
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A data-physics hybrid generative model for patient-specific post-stroke motor rehabilitation using wearable sensor data

arXiv:2512.14329v1 Announce Type: cross Abstract: Dynamic prediction of locomotor capacity after stroke is crucial for tailoring rehabilitation, yet current assessments provide only static impairment scores and do not indicate whether patients can safely perform specific tasks such as slope walking or stair climbing. Here, we develop a data-physics hybrid generative framework that reconstructs an individual stroke survivor's neuromuscular control from a single 20 m level-ground walking trial and predicts task-conditioned locomotion across rehabilitation scenarios. The system combines wearable-sensor kinematics, a proportional-derivative physics controller, a population Healthy Motion Atlas, and goal-conditioned deep reinforcement learning with behaviour cloning and generative adversarial imitation learning to generate physically plausible, patient-specific gait simulations for slopes and stairs. In 11 stroke survivors, the personalized controllers preserved idiosyncratic gait patterns while improving joint-angle and endpoint fidelity by 4.73% and 12.10%, respectively, and reducing training time to 25.56% relative to a physics-only baseline. In a multicentre pilot involving 21 inpatients, clinicians who used our locomotion predictions to guide task selection and difficulty obtained larger gains in Fugl-Meyer lower-extremity scores over 28 days of standard rehabilitation than control clinicians (mean change 6.0 versus 3.7 points). These findings indicate that our generative, task-predictive framework can augment clinical decision-making in post-stroke gait rehabilitation and provide a template for dynamically personalized motor recovery strategies.
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Genotype-Phenotype Integration through Machine Learning and Personalized Gene Regulatory Networks for Cancer Metastasis Prediction

arXiv:2510.23620v1 Announce Type: cross Abstract: Metastasis is the leading cause of cancer-related mortality, yet most predictive models rely on shallow architectures and neglect patient-specific regulatory mechanisms. Here, we integrate classical machine learning and deep learning to predict metastatic potential across multiple cancer types. Gene expression profiles from the Cancer Cell Line Encyclopedia were combined with a transcription factor-target prior from DoRothEA, focusing on nine metastasis-associated regulators. After selecting differential genes using the Kruskal-Wallis test, ElasticNet, Random Forest, and XGBoost models were trained for benchmarking. Personalized gene regulatory networks were then constructed using PANDA and LIONESS and analyzed through a graph attention neural network (GATv2) to learn topological and expression-based representations. While XGBoost achieved the highest AUROC (0.7051), the GNN captured non-linear regulatory dependencies at the patient level. These results demonstrate that combining traditional machine learning with graph-based deep learning enables a scalable and interpretable framework for metastasis risk prediction in precision oncology.
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Thor: a platform for cell-level investigation of spatial transcriptomics and histology

Nat Commun. 2025 Aug 5;16(1):7178. doi: 10.1038/s41467-025-62593-1.

ABSTRACT

Spatial transcriptomics links gene expression with tissue morphology, however, current tools often prioritize genomic analysis, lacking integrated image interpretation. To address this, we present Thor, a comprehensive platform for cell-level analysis of spatial transcriptomics and histological images. Thor employs an anti-shrinking Markov diffusion method to infer single-cell spatial transcriptome from spot-level data, effectively combining gene expression and cell morphology. The platform includes 10 modular tools for genomic and image-based analysis, and is paired with Mjolnir, a web-based interface for interactive exploration of gigapixel images. Thor is validated on simulated data and multiple spatial platforms (ISH, MERFISH, Xenium, Stereo-seq). Thor characterizes regenerative signatures in heart failure, screens breast cancer hallmarks, resolves fine layers in mouse olfactory bulb, and annotates fibrotic heart tissue. In high-resolution Visium HD data, it enhances spatial gene patterns aligned with histology. By bridging transcriptomic and histological analysis, Thor enables holistic tissue interpretation in spatial biology.

PMID:40764306 | PMC:PMC12325965 | DOI:10.1038/s41467-025-62593-1

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