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Dec 11

Multimodal AI predicts clinical outcomes of drug combinations from preclinical data

Predicting clinical outcomes from preclinical data is essential for identifying safe and effective drug combinations. Current models rely on structural or target-based features to identify high-efficacy, low-toxicity drug combinations. However, these approaches 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 21842 compounds, including combinations of approved drugs and novel compounds in development. MADRIGAL uses a transformer 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. MADRIGAL performs virtual screening of anticancer drug combinations and supports polypharmacy management for type II diabetes and metabolic dysfunction-associated steatohepatitis (MASH). It identifies transporter-mediated drug interactions. MADRIGAL predicts resmetirom, the first and only FDA-approved drug for MASH, among therapies with the most favorable safety profile. It supports personalized cancer therapy by integrating genomic profiles from cancer patients. Using primary acute myeloid leukemia samples and patient-derived xenograft models, it predicts the efficacy of personalized drug combinations. Integrating MADRIGAL with a large language model allows users to describe clinical outcomes in natural language, improving safety assessment by identifying potential adverse interactions and toxicity risks. MADRIGAL provides a multimodal approach for designing combination therapies with improved predictive accuracy and clinical relevance.

  • 10 authors
·
Mar 4

CLIPort: What and Where Pathways for Robotic Manipulation

How can we imbue robots with the ability to manipulate objects precisely but also to reason about them in terms of abstract concepts? Recent works in manipulation have shown that end-to-end networks can learn dexterous skills that require precise spatial reasoning, but these methods often fail to generalize to new goals or quickly learn transferable concepts across tasks. In parallel, there has been great progress in learning generalizable semantic representations for vision and language by training on large-scale internet data, however these representations lack the spatial understanding necessary for fine-grained manipulation. To this end, we propose a framework that combines the best of both worlds: a two-stream architecture with semantic and spatial pathways for vision-based manipulation. Specifically, we present CLIPort, a language-conditioned imitation-learning agent that combines the broad semantic understanding (what) of CLIP [1] with the spatial precision (where) of Transporter [2]. Our end-to-end framework is capable of solving a variety of language-specified tabletop tasks from packing unseen objects to folding cloths, all without any explicit representations of object poses, instance segmentations, memory, symbolic states, or syntactic structures. Experiments in simulated and real-world settings show that our approach is data efficient in few-shot settings and generalizes effectively to seen and unseen semantic concepts. We even learn one multi-task policy for 10 simulated and 9 real-world tasks that is better or comparable to single-task policies.

  • 3 authors
·
Sep 24, 2021