Clinical oncology generates vast, unstructured data that often contain inconsistencies, missing information, and ambiguities, making it difficult to extract reliable insights for data-driven decision-making. General-purpose large language models (LLMs) struggle with these challenges due to their lack of domain-specific reasoning, including specialized clinical terminology, context-dependent interpretations, and multi-modal data integration. We address these issues with an oncology-specialized, efficient, and adaptable NLP framework that combines instruction tuning, retrieval-augmented generation (RAG), and graph-based knowledge integration. Our lightweight models prove effective at oncology-specific tasks, such as named entity recognition (e.g., identifying cancer diagnoses), entity linking (e.g., linking entities to standardized ontologies), TNM staging, document classification (e.g., cancer subtype classification from pathology reports), and treatment response prediction. Our framework emphasizes adaptability and resource efficiency. We include minimal German instructions, collected at the University Hospital Zurich (USZ), to test whether small amounts of non-English language data can effectively transfer knowledge across languages. This approach mirrors our motivation for lightweight models, which balance strong performance with reduced computational costs, making them suitable for resource-limited healthcare settings. We validated our models on oncology datasets, demonstrating strong results in named entity recognition, relation extraction, and document classification.

Capturing subtle speech disruptions across the psychosis spectrum is challenging because of the inherent variability in speech patterns. This variability reflects individual differences and the fluctuating nature of symptoms in both clinical and non-clinical populations. Accounting for uncertainty in speech data is essential for predicting symptom severity and improving diagnostic precision. Speech disruptions characteristic of psychosis appear across the spectrum, including in non-clinical individuals. We develop an uncertainty-aware model integrating acoustic and linguistic features to predict symptom severity and psychosis-related traits. Quantifying uncertainty in specific modalities allows the model to address speech variability, improving prediction accuracy. We analyzed speech data from 114 participants, including 32 individuals with early psychosis and 82 with low or high schizotypy, collected through structured interviews, semi-structured autobiographical tasks, and narrative-driven interactions in German. The model improved prediction accuracy, reducing RMSE and achieving an F1-score of 83% with ECE = 4.5e-2, showing robust performance across different interaction contexts. Uncertainty estimation improved model interpretability by identifying reliability differences in speech markers such as pitch variability, fluency disruptions, and spectral instability. The model dynamically adjusted to task structures, weighting acoustic features more in structured settings and linguistic features in unstructured contexts. This approach strengthens early detection, personalized assessment, and clinical decision-making in psychosis-spectrum research.

X-rays have played a fundamental role in medicine since their discovery in 1895 (Röntgen, 1895), and continue to be the most frequently used medical imaging modality worldwide due to their convenience and cost-effectiveness (Akhter et al., 2023). Chest X-ray (CXR) remains the most commonly performed radiological exam globally, particularly important for diagnosing and monitoring thoracic conditions such as pneumonia, heart failure, and lung cancer (Çallı et al., 2021). Problematically, the growing volume of CXRs and other imaging studies in recent years have lead to a reduction in the time available for radiologists to thoroughly evaluate each case (Peng et al., 2022). As a result, in many countries, the responsibility of interpreting CXRs is often transferred to non-radiology physicians, who typically possess less specialized training and experience. This shift increases the risk of diagnostic errors or misinterpretations (Shammari et al., 2021; Peng et al., 2022). The shortage of trained personnel for CXR interpretation has led to the exploration of automated agents to assist physicians in diagnostic tasks. In recent years, various deep learning models have shown promise in clinical applications, such as the detection of conditions like COVID-19 pneumonia (Nishio et al., 2020) or pulmonary nodules (Homayounieh et al., 2021). Another extensively studied task is the automated generation of free text reports from CXR images using transformer-based architectures (Nooralahzadeh et al., 2021; Yang et al., 2023; Hyland et al., 2023; Chaves et al., 2024). These models can provide preliminary drafts summarizing key observations from the CXR, offering a potential enhancement to the diagnostic workflow.

The goal of protein fitness optimization is to discover new protein variants with enhanced fitness for a given use. The vast search space and the sparsely populated fitness landscape, along with the discrete nature of protein sequences, pose significant challenges when trying to determine the gradient towards configurations with higher fitness. We introduce Variational Latent Generative Protein Optimization (VLGPO), a variational perspective on fitness optimization. Our method embeds protein sequences in a continuous latent space to enable efficient sampling from the fitness distribution and combines a (learned) flow matching prior over sequence mutations with a fitness predictor to guide optimization towards sequences with high fitness. VLGPO achieves state-of-the-art results on two different protein benchmarks of varying complexity. Moreover, the variational design with explicit prior and likelihood functions offers a flexible plug-and-play framework that can be easily customized to suit various protein design tasks.

We propose TAMER, a Test-time Adaptive MoE-driven framework for EHR Representation learning. TAMER combines a Mixture-of-Experts (MoE) with Test-Time Adaptation (TTA) to address two critical challenges in EHR modeling: patient population heterogeneity and distribution shifts. The MoE component handles diverse patient subgroups, while TTA enables real-time adaptation to evolving health status distributions when new patient samples are introduced. Extensive experiments across four real-world EHR datasets demonstrate that TAMER consistently improves predictive performance for both mortality and readmission risk tasks when combined with diverse EHR modeling backbones. TAMER offers a promising approach for dynamic and personalized EHR-based predictions in practical clinical settings. Code is publicly available at https://github.com/yhzhu99/TAMER.

Precision medicine has the potential to tailor treatment decisions to individual patients using machine learning (ML) and artificial intelligence (AI), but it faces significant challenges due to complex biases in clinical observational data and the high-dimensional nature of biological data. This study models various types of treatment assignment biases using mutual information and investigates their impact on ML models for counterfactual prediction and biomarker identification. Unlike traditional counterfactual benchmarks that rely on fixed treatment policies, our work focuses on modeling different characteristics of the underlying observational treatment policy in distinct clinical settings. We validate our approach through experiments on toy datasets, semi-synthetic tumor cancer genome atlas (TCGA) data, and real-world biological outcomes from drug and CRISPR screens. By incorporating empirical biological mechanisms, we create a more realistic benchmark that reflects the complexities of real-world data. Our analysis reveals that different biases lead to varying model performances, with some biases, especially those unrelated to outcome mechanisms, having minimal effect on prediction accuracy. This highlights the crucial need to account for specific biases in clinical observational data in counterfactual ML model development, ultimately enhancing the personalization of treatment decisions in precision medicine.

We propose a deep generative approach using latent temporal processes for modeling and holistically analyzing complex disease trajectories, with a particular focus on Systemic Sclerosis (SSc). We aim to learn temporal latent representations of the underlying generative process that explain the observed patient disease trajectories in an interpretable and comprehensive way. To enhance the interpretability of these latent temporal processes, we develop a semi-supervised approach for disentangling the latent space using established medical knowledge. By combining the generative approach with medical definitions of different characteristics of SSc, we facilitate the discovery of new aspects of the disease. We show that the learned temporal latent processes can be utilized for further data analysis and clinical hypothesis testing, including finding similar patients and clustering SSc patient trajectories into novel sub-types. Moreover, our method enables personalized online monitoring and prediction of multivariate time series with uncertainty quantification.

The identification of phenotypes within complex diseases or syndromes is a fundamental component of precision medicine, which aims to adapt healthcare to individual patient characteristics. Postoperative delirium (POD) is a complex neuropsychiatric condition with significant heterogeneity in its clinical manifestations and underlying pathophysiology. We hypothesize that POD comprises several distinct phenotypes, which cannot be directly observed in clinical practice. Identifying these phenotypes could enhance our understanding of POD pathogenesis and facilitate the development of targeted prevention and treatment strategies. In this paper, we propose an approach that combines supervised machine learning for personalized POD risk prediction with unsupervised clustering techniques to uncover potential POD phenotypes. We first demonstrate our approach using synthetic data, where we simulate patient cohorts with predefined phenotypes based on distinct sets of informative features. We aim to mimic any clinical disease with our synthetic data generation method. By training a predictive model and applying SHAP, we show that clustering patients in the SHAP feature importance space successfully recovers the true underlying phenotypes, outperforming clustering in the raw feature space. We then present a case study using real-world data from a cohort of elderly surgical patients. The results showcase the utility of our approach in uncovering clinically relevant subtypes of complex disorders like POD, paving the way for more precise and personalized treatment strategies.

Irregular multivariate time series data is characterized by varying time intervals between consecutive observations of measured variables/signals (i.e., features) and varying sampling rates (i.e., recordings/measurement) across these features. Modeling time series while taking into account these irregularities is still a challenging task for machine learning methods. Here, we introduce TADA, a Two-stageAggregation process with Dynamic local Attention to harmonize time-wise and feature-wise irregularities in multivariate time series. In the first stage, the irregular time series undergoes temporal embedding (TE) using all available features at each time step. This process preserves the contribution of each available feature and generates a fixed-dimensional representation per time step. The second stage introduces a dynamic local attention (DLA) mechanism with adaptive window sizes. DLA aggregates time recordings using feature-specific windows to harmonize irregular time intervals capturing feature-specific sampling rates. Then hierarchical MLP mixer layers process the output of DLA through multiscale patching to leverage information at various scales for the downstream tasks. TADA outperforms state-of-the-art methods on three real-world datasets, including the latest MIMIC IV dataset, and highlights its effectiveness in handling irregular multivariate time series and its potential for various real-world applications.

AI-driven precision oncology has the transformative potential to reshape cancer treatment by leveraging the power of AI models to analyze the interaction between complex patient characteristics and their corresponding treatment outcomes. New technological platforms have facilitated the timely acquisition of multimodal data on tumor biology at an unprecedented resolution, such as single-cell multi-omics data, making this quality and quantity of data available for data-driven improved clinical decision-making. In this work, we propose a modular machine learning framework designed for personalized counterfactual cancer treatment suggestions based on an ensemble of machine learning experts trained on diverse multi-omics technologies. These specialized counterfactual experts per technology are consistently aggregated into a more powerful expert with superior performance and can provide both confidence and an explanation of its decision. The framework is tailored to address critical challenges inherent in data-driven cancer research, including the high-dimensional nature of the data, and the presence of treatment assignment bias in the retrospective observational data. The framework is showcased through comprehensive demonstrations using data from in-vitro and in-vivo treatment responses from a cohort of patients with ovarian cancer. Our method aims to empower clinicians with a reality-centric decision-support tool including probabilistic treatment suggestions with calibrated confidence and personalized explanations for tailoring treatment strategies to multi-omics characteristics of individual cancer patients.