Spatial proteomics technologies have transformed our understanding of complex tissue architectures by enabling simultaneous analysis of multiple molecular markers and their spatial organization. The high dimensionality of these data, varying marker combinations across experiments and heterogeneous study designs pose unique challenges for computational analysis. Here, we present Virtual Tissues (VirTues), a foundation model framework for biological tissues that operates across the molecular, cellular and tissue scale. VirTues introduces innovations in transformer architecture design, including a novel tokenization scheme that captures both spatial and marker dimensions, and attention mechanisms that scale to high-dimensional multiplex data while maintaining interpretability. Trained on diverse cancer and non-cancer tissue datasets, VirTues demonstrates strong generalization capabilities without task-specific fine-tuning, enabling cross-study analysis and novel marker integration. As a generalist model, VirTues outperforms existing approaches across clinical diagnostics, biological discovery and patient case retrieval tasks, while providing insights into tissue function and disease mechanisms.

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.

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.