Varun Ullanat

Yepeng Huang, Xiaorui Su, Varun Ullanat et al.

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations, reducing late-stage clinical failures, and accelerating the development of precision therapies. Current AI models rely on structural or target-based features but fail to incorporate the multimodal data necessary for accurate, clinically relevant predictions. Here, we introduce Madrigal, a multimodal AI model that learns from structural, pathway, cell viability, and transcriptomic data to predict drug-combination effects across 953 clinical outcomes and 21,842 compounds, including combinations of approved drugs and novel compounds in development. Madrigal uses an attention bottleneck module to unify preclinical drug data modalities while handling missing data during training and inference, a major challenge in multimodal learning. It outperforms single-modality methods and state-of-the-art models in predicting adverse drug interactions, and ablations show both modality alignment and multimodality are necessary. It captures transporter-mediated interactions and aligns with head-to-head clinical trial differences for neutropenia, anemia, alopecia, and hypoglycemia. In type 2 diabetes and MASH, Madrigal supports polypharmacy decisions and prioritizes resmetirom among safer candidates. Extending to personalization, Madrigal improves patient-level adverse-event prediction in a longitudinal EHR cohort and an independent oncology cohort, and predicts ex vivo efficacy in primary acute myeloid leukemia samples and patient-derived xenograft models. Madrigal links preclinical multimodal readouts to safety risks of drug combinations and offers a generalizable foundation for safer combination design.

Mohamed Omar, Giuseppe Nicolo Fanelli, Fabio Socciarelli et al.

Conventional histopathology has long been essential for disease diagnosis, relying on visual inspection of tissue sections. Immunohistochemistry aids in detecting specific biomarkers but is limited by its single-marker approach, restricting its ability to capture the full tissue environment. The advent of multiplexed imaging technologies, like multiplexed immunofluorescence and spatial transcriptomics, allows for simultaneous visualization of multiple biomarkers in a single section, enhancing morphological data with molecular and spatial information. This provides a more comprehensive view of the tissue microenvironment, cellular interactions, and disease mechanisms - crucial for understanding disease progression, prognosis, and treatment response. However, the extensive data from multiplexed imaging necessitates sophisticated computational methods for preprocessing, segmentation, feature extraction, and spatial analysis. These tools are vital for managing large, multidimensional datasets, converting raw imaging data into actionable insights. By automating labor-intensive tasks and enhancing reproducibility and accuracy, computational tools are pivotal in diagnostics and research. This review explores the current landscape of multiplexed imaging in pathology, detailing workflows and key technologies like PathML, an AI-powered platform that streamlines image analysis, making complex dataset interpretation accessible for clinical and research settings.

James Wen, Sahil Nalawade, Zhiwei Liang et al. · deepmind, harvard

Background: Generative artificial intelligence (AI) deployment in academic medical settings raises copyright compliance concerns. Dana-Farber Cancer Institute implemented GPT4DFCI, an internal generative AI tool utilizing OpenAI models, that is approved for enterprise use in research and operations. Given (1) the exceptionally broad adoption of the tool in our organization, (2) our research mission, and (3) the shared responsibility model required to benefit from Customer Copyright Commitment in Azure OpenAI Service products, we deemed rigorous copyright compliance testing necessary. Case Description: We conducted a structured red teaming exercise in Nov. 2024, with 42 participants from academic, industry, and government institutions. Four teams attempted to extract copyrighted content from GPT4DFCI across four domains: literary works, news articles, scientific publications, and access-restricted clinical notes. Teams successfully extracted verbatim book dedications and near-exact passages through various strategies. News article extraction failed despite jailbreak attempts. Scientific article reproduction yielded only high-level summaries. Clinical note testing revealed appropriate privacy safeguards. Discussion: The successful extraction of literary content indicates potential copyrighted material presence in training data, necessitating inference-time filtering. Differential success rates across content types suggest varying protective mechanisms. The event led to implementation of a copyright-specific meta-prompt in GPT4DFCI; this mitigation has been in production since Jan. 2025. Conclusion: Systematic red teaming revealed specific vulnerabilities in generative AI copyright compliance, leading to concrete mitigation strategies. Academic medical institutions deploying generative AI should implement continuous testing protocols to ensure legal and ethical compliance.