Noa Dagan

Aashna P. Shah, Michelle M. Li, Yash Lal et al.

Blood-based biomarkers underpin clinical diagnosis and management, yet their interpretation relies largely on fixed population reference intervals that ignore stable, intra-patient variability. As such, population-based interpretation can mask meaningful deviation from an individual's baseline, risking delayed disease detection. To remedy this, there have been increasing efforts to personalize blood biomarker interpretation using individual testing histories. However, these methods may overfit to sparse data, inflating false-positive rates and unnecessary follow-up, and can also unwittingly include unrecognized or subclinical disease. Here, we leverage nearly 2 billion longitudinal laboratory measurements from over 1.6 million individuals across North America, the Middle East, and East Asia, to show that while laboratory values are highly individual, purely personalized intervals routinely overfit, classifying up to 68% of measurements as abnormal, without corresponding associations with adverse clinical outcomes. We then introduce NORMA, a conditional transformer-based framework that generates reference intervals by conditioning on both a patient's history and population-level data about "normal" variation. NORMA-derived intervals achieve higher precision for predicting outcomes, including mortality, acute kidney injury, and chronic disease. These findings caution against over-personalization in laboratory medicine and demonstrate that anchoring individual trajectories to population-level priors outperforms either approach alone. To promote transparency, we publicly release the model, code, and an interactive user interface for accessible, individualized laboratory interpretation.

Payal Chandak, Victoria Alkin, David Wu et al.

Medicine is inherently pluralistic. Principles such as autonomy, beneficence, nonmaleficence, and justice routinely conflict, and such ethical dilemmas often sharply divide reasonable physicians. Good clinical practice navigates these tensions in concert with each patient's values rather than imposing a single ethical stance. The ethical values that large language models bring to medical advice, however, have not been systematically examined. We present a framework for auditing value pluralism in medical AI, comprising a benchmark of clinician-verified dilemmas and an attribution method that recovers value priorities directly from decisions. The ecosystem of frontier models spans physician-level value heterogeneity, and models discuss competing values in their reasoning (Overton pluralism) before committing to a decision. However, individual model decisions are near-deterministic across repeated sampling and semantic variations, failing to reproduce the distributional pluralism of the physician panel. Across benchmark cases, these consistent decisions reflect committed, systematic value preferences. While most model priorities fall within the natural range of inter-physician variation, some significantly underweight patient autonomy. A single LLM deployed without regard for its value priorities could amplify those priorities at scale to every patient it serves. Without explicit efforts to balance ethical perspectives with one or multiple models, these tools risk replacing clinical pluralism with a deployment monoculture.

Ayush Noori, Joaquín Polonuer, Katharina Meyer et al.

Neurological diseases are the leading global cause of disability, yet most lack disease-modifying treatments. We present PROTON, a heterogeneous graph transformer that generates testable hypotheses across molecular, organoid, and clinical systems. To evaluate PROTON, we apply it to Parkinson's disease (PD), bipolar disorder (BD), and Alzheimer's disease (AD). In PD, PROTON linked genetic risk loci to genes essential for dopaminergic neuron survival and predicted pesticides toxic to patient-derived neurons, including the insecticide endosulfan, which ranked within the top 1.29% of predictions. In silico screens performed by PROTON reproduced six genome-wide $α$-synuclein experiments, including a split-ubiquitin yeast two-hybrid system (normalized enrichment score [NES] = 2.30, FDR-adjusted $p < 1 \times 10^{-4}$), an ascorbate peroxidase proximity labeling assay (NES = 2.16, FDR $< 1 \times 10^{-4}$), and a high-depth targeted exome sequencing study in 496 synucleinopathy patients (NES = 2.13, FDR $< 1 \times 10^{-4}$). In BD, PROTON predicted calcitriol as a candidate drug that reversed proteomic alterations observed in cortical organoids derived from BD patients. In AD, we evaluated PROTON predictions in health records from $n = 610,524$ patients at Mass General Brigham, confirming that five PROTON-predicted drugs were associated with reduced seven-year dementia risk (minimum hazard ratio = 0.63, 95% CI: 0.53-0.75, $p < 1 \times 10^{-7}$). PROTON generated neurological hypotheses that were evaluated across molecular, organoid, and clinical systems, defining a path for AI-driven discovery in neurological disease.

Ayush Noori, Adam Rodman, Alan Karthikesalingam et al.

Modern computer systems often rely on syslog, a simple, universal protocol that records every critical event across heterogeneous infrastructure. However, healthcare's rapidly growing clinical AI stack has no equivalent. As hospitals rush to pilot large language models and other AI-based clinical decision support tools, we still lack a standard way to record how, when, by whom, and for whom these AI models are used. Without that transparency and visibility, it is challenging to measure real-world performance and outcomes, detect adverse events, or correct bias or dataset drift. In the spirit of syslog, we introduce MedLog, a protocol for event-level logging of clinical AI. Any time an AI model is invoked to interact with a human, interface with another algorithm, or act independently, a MedLog record is created. This record consists of nine core fields: header, model, user, target, inputs, artifacts, outputs, outcomes, and feedback, providing a structured and consistent record of model activity. To encourage early adoption, especially in low-resource settings, and minimize the data footprint, MedLog supports risk-based sampling, lifecycle-aware retention policies, and write-behind caching; detailed traces for complex, agentic, or multi-stage workflows can also be captured under MedLog. MedLog can catalyze the development of new databases and software to store and analyze MedLog records. Realizing this vision would enable continuous surveillance, auditing, and iterative improvement of medical AI, laying the foundation for a new form of digital epidemiology.

Tomer D. Meirman, Bracha Shapira, Noa Dagan et al.

Interpretable risk scores play a vital role in clinical decision support, yet traditional methods for deriving such scores often rely on manual preprocessing, task-specific modeling, and simplified assumptions that limit their flexibility and predictive power. We present SHAPoint, a novel, task-agnostic framework that integrates the predictive accuracy of gradient boosted trees with the interpretability of point-based risk scores. SHAPoint supports classification, regression, and survival tasks, while also inheriting valuable properties from tree-based models, such as native handling of missing data and support for monotonic constraints. Compared to existing frameworks, SHAPoint offers superior flexibility, reduced reliance on manual preprocessing, and faster runtime performance. Empirical results show that SHAPoint produces compact and interpretable scores with predictive performance comparable to state-of-the-art methods, but at a fraction of the runtime, making it a powerful tool for transparent and scalable risk stratification.

Michelle M. Li, Ben Y. Reis, Adam Rodman et al.

Medical AI, including clinical language models, vision-language models, and multimodal health record models, already summarizes notes, answers questions, and supports decisions. Their adaptation to new populations, specialties, or care settings often relies on fine-tuning, prompting, or retrieval from external knowledge bases. These strategies can scale poorly and risk contextual errors: outputs that appear plausible but miss critical patient or situational information. We envision context switching as a solution. Context switching adjusts model reasoning at inference without retraining. Generative models can tailor outputs to patient biology, care setting, or disease. Multimodal models can reason on notes, laboratory results, imaging, and genomics, even when some data are missing or delayed. Agent models can coordinate tools and roles based on tasks and users. In each case, context switching enables medical AI to adapt across specialties, populations, and geographies. It requires advances in data design, model architectures, and evaluation frameworks, and establishes a foundation for medical AI that scales to infinitely many contexts while remaining reliable and suited to real-world care.