Artificial intelligence (AI) has become increasingly central to precision medicine by enabling the integration and interpretation of multimodal data, yet implementation in clinical settings remains limited. This paper provides a scoping review of literature from 2019-2024 on the implementation of AI in precision medicine, identifying key barriers and enablers across data quality, clinical reliability, workflow integration, and governance. Through an ecosystem-based framework, we highlight the interdependent relationships shaping real-world translation and propose future directions to support trustworthy and sustainable implementation. Traditional healthcare models have difficulty addressing the complexity of modern healthcare needs, particularly given the increasingly multimodal nature of health data spanning genetic, clinical, behavioral, environmental, and lifestyle information (Topol, 2023; Judge et al., 2024; Schouten et al., 2025). As precision medicine emerges as a promising solution for integrating multimodal data into healthcare, a new implementation strategy is necessary due to the complexity of existing healthcare structures and the extent of interdisciplinary collaboration that is now required (Tobias et al., 2023).

Machine learning in medicine is typically optimized for population averages. This frequency-weighted training privileges common presentations and marginalizes rare yet clinically critical cases, a bias we call the average patient fallacy. In mixture models, gradients from rare cases are suppressed by prevalence, creating a direct conflict with precision medicine. Clinical vignettes in oncology, cardiology, and ophthalmology show how this yields missed rare responders, delayed recognition of atypical emergencies, and underperformance on vision-threatening variants. We propose operational fixes: Rare Case Performance Gap, Rare-Case Calibration Error, a prevalence-utility definition of rarity, and clinically weighted objectives that surface ethical priorities. Weight selection should follow structured deliberation. AI in medicine must detect exceptional cases because of their significance.

Metabolic disorders, particularly type 2 diabetes mellitus (T2DM), represent a significant global health burden, disproportionately impacting genetically predisposed populations such as the Pima Indians (a Native American tribe from south central Arizona). This study introduces a novel machine learning (ML) framework that integrates predictive modeling with gene-agnostic pathway mapping to identify high-risk individuals and uncover potential therapeutic targets. Using the Pima Indian dataset, logistic regression and t-tests were applied to identify key predictors of T2DM, yielding an overall model accuracy of 78.43%. To bridge predictive analytics with biological relevance, we developed a pathway mapping strategy that links identified predictors to critical signaling networks, including insulin signaling, AMPK, and PPAR pathways. This approach provides mechanistic insights without requiring direct molecular data. Building upon these connections, we propose therapeutic strategies such as dual GLP-1/GIP receptor agonists, AMPK activators, SIRT1 modulators, and phytochemical, further validated through pathway enrichment analyses. Overall, this framework advances precision medicine by offering interpretable and scalable solutions for early detection and targeted intervention in metabolic disorders. The key contributions of this work are: (1) development of an ML framework combining logistic regression and principal component analysis (PCA) for T2DM risk prediction; (2) introduction of a gene-agnostic pathway mapping approach to generate mechanistic insights; and (3) identification of novel therapeutic strategies tailored for high-risk populations.

With the timely formation of personalized intervention plans based on high-dimensional heterogeneous time series information has become an important challenge in the medical field today . As electronic medical records, wearables and other multi-source medical data are increasingly generated and diversified. In this work, we develop a system to generate personalized medical intervention strategies based on Group Relative Policy Optimization (GRPO) and Time-Series Data Fusion: First by incorporating relative policy constraints among the groups during policy gradient updates adaptive balance the individual gain and group gain distribution. To improve the robustness and interpretability of decision-making, the multi-layer neural network structure was employed to group code the patient characteristics. Secondly, for the rapid multi-modal fusion of multi -source heterogeneous time series, a multi -channel neural network combined with self -attention mechanism was employed for dynamic feature extraction, the key feature screening and aggregation were further achieved through the differentiable gating network. Finally, a collaborative search process was proposed to find the ideal candidate intervention strategy based on the combination of genetic algorithm and Monte Carlo tree search so that a global optimization of the candidate intervention strategies was achieved, which greatly enhanced the accuracy of the system as well a s the system's personalization level. The experimental results show that model achieves significant improvement in aspects of accuracy, coverage and decision -making benefits of intervention effect compared with existing methods.

Artificial intelligence (AI) is poised to transform healthcare by enabling personalized and efficient care through data-driven insights. Although radiology is at the forefront of AI adoption, in practice, the potential of AI models is often overshadowed by severe failures to generalize: AI models can have performance degradation of up to 20% when transitioning from controlled test environments to clinical use by radiologists. This mismatch raises concerns that radiologists will be misled by incorrect AI predictions in practice and/or grow to distrust AI, rendering these promising technologies practically ineffectual. Exhaustive clinical trials of AI models on abundant and diverse data is thus critical to anticipate AI model degradation when encountering varied data samples. Achieving these goals, however, is challenging due to the high costs of collecting diverse data samples and corresponding annotations. To overcome these limitations, we introduce a novel conditional generative AI model designed for virtual clinical trials (VCTs) of radiology AI, capable of realistically synthesizing full-body CT images of patients with specified attributes. By learning the joint distribution of images and anatomical structures, our model enables precise replication of real-world patient populations with unprecedented detail at this scale. We demonstrate meaningful evaluation of radiology AI models through VCTs powered by our synthetic CT study populations, revealing model degradation and facilitating algorithmic auditing for bias-inducing data attributes. Our generative AI approach to VCTs is a promising avenue towards a scalable solution to assess model robustness, mitigate biases, and safeguard patient care by enabling simpler testing and evaluation of AI models in any desired range of diverse patient populations.

The integration of artificial intelligence [AI] into clinical trials has revolutionized the process of drug development and personalized medicine. Among these advancements, deep learning and predictive modelling have emerged as transformative tools for optimizing clinical trial design, patient recruitment, and real-time monitoring. This study explores the application of deep learning techniques, such as convolutional neural networks [CNNs] and transformerbased models, to stratify patients, forecast adverse events, and personalize treatment plans. Furthermore, predictive modelling approaches, including survival analysis and time-series forecasting, are employed to predict trial outcomes, enhancing efficiency and reducing trial failure rates. To address challenges in analysing unstructured clinical data, such as patient notes and trial protocols, natural language processing [NLP] techniques are utilized for extracting actionable insights. A custom dataset comprising structured patient demographics, genomic data, and unstructured text is curated for training and validating these models. Key metrics, including precision, recall, and F1 scores, are used to evaluate model performance, while trade-offs between accuracy and computational efficiency are examined to identify the optimal model for clinical deployment. This research underscores the potential of AI-driven methods to streamline clinical trial workflows, improve patient-centric outcomes, and reduce costs associated with trial inefficiencies. The findings provide a robust framework for integrating predictive analytics into precision medicine, paving the way for more adaptive and efficient clinical trials. By bridging the gap between technological innovation and real-world applications, this study contributes to advancing the role of AI in healthcare, particularly in fostering personalized care and improving overall trial success rates.

The success of precision medicine requires computational models that can effectively process and interpret diverse physiological signals across heterogeneous patient populations. While foundation models have demonstrated remarkable transfer capabilities across various domains, their effectiveness in handling individual-specific physiological signals - crucial for precision medicine - remains largely unexplored. This work introduces a systematic pipeline for rapidly and efficiently evaluating foundation models' transfer capabilities in medical contexts. Our pipeline employs a three-stage approach. First, it leverages physiological simulation software to generate diverse, clinically relevant scenarios, particularly focusing on data-scarce medical conditions. This simulation-based approach enables both targeted capability assessment and subsequent model fine-tuning. Second, the pipeline projects these simulated signals through the foundation model to obtain embeddings, which are then evaluated using linear methods. This evaluation quantifies the model's ability to capture three critical aspects: physiological feature independence, temporal dynamics preservation, and medical scenario differentiation. Finally, the pipeline validates these representations through specific downstream medical tasks. Initial testing of our pipeline on the Moirai time series foundation model revealed significant limitations in physiological signal processing, including feature entanglement, temporal dynamics distortion, and reduced scenario discrimination. These findings suggest that current foundation models may require substantial architectural modifications or targeted fine-tuning before deployment in clinical settings.

AI is a magnificent field that directly and profoundly touches on numerous disciplines ranging from philosophy, computer science, engineering, mathematics, decision and data science and economics, to cognitive science, neuroscience and more. The number of applications and impact of AI is second to none and the potential of AI to broadly impact future science developments is particularly thrilling. While attempts to understand knowledge, reasoning, cognition and learning go back centuries, AI remains a relatively new field. In part due to the fact it has so many wide-ranging overlaps with other disparate fields it appears to have trouble developing a robust identity and culture. Here we suggest that contrasting the fast-moving AI culture to biological and biomedical sciences is both insightful and useful way to inaugurate a healthy tradition needed to envision and manage our ascent to AGI and beyond (independent of the AI Platforms used). The co-evolution of AI and Biomedical Science offers many benefits to both fields. In a previous perspective, we suggested that biomedical laboratories or centers can usefully embrace logistic traditions in AI labs that will allow them to be highly collaborative, improve the reproducibility of research, reduce risk aversion and produce faster mentorship pathways for PhDs and fellows. This perspective focuses on the benefits to AI by adapting features of biomedical science at higher, primarily cultural levels.

Rare gynecological tumors (RGTs) present major clinical challenges due to their low incidence and heterogeneity. The lack of clear guidelines leads to suboptimal management and poor prognosis. Molecular tumor boards accelerate access to effective therapies by tailoring treatment based on biomarkers, beyond cancer type. Unstructured data that requires manual curation hinders efficient use of biomarker profiling for therapy matching. This study explores the use of large language models (LLMs) to construct digital twins for precision medicine in RGTs. Our proof-of-concept digital twin system integrates clinical and biomarker data from institutional and published cases (n=21) and literature-derived data (n=655 publications with n=404,265 patients) to create tailored treatment plans for metastatic uterine carcinosarcoma, identifying options potentially missed by traditional, single-source analysis. LLM-enabled digital twins efficiently model individual patient trajectories. Shifting to a biology-based rather than organ-based tumor definition enables personalized care that could advance RGT management and thus enhance patient outcomes.

The concept of personalised medicine in cancer therapy is becoming increasingly important. There already exist drugs administered specifically for patients with tumours presenting well-defined mutations. However, the field is still in its infancy, and personalised treatments are far from being standard of care. Personalised medicine is often associated with the utilisation of omics data. Yet, implementation of multi-omics data has proven difficult, due to the variety and scale of the information within the data, as well as the complexity behind the myriad of interactions taking place within the cell. An alternative approach to precision medicine is to employ a function-based profile of the cell. This involves screening a range of drugs against patient derived cells. Here we demonstrate a proof-of-concept, where a collection of drug screens against a highly diverse set of patient-derived cell lines, are leveraged to identify putative treatment options for a 'new patient'. We show that this methodology is highly efficient in ranking the drugs according to their activity towards the target cells. We argue that this approach offers great potential, as activities can be efficiently imputed from various subsets of the drug treated cell lines that do not necessarily originate from the same tissue type.