Foundation models are reshaping computational pathology by enabling transfer learning, where models pre-trained on vast datasets can be adapted for downstream diagnostic, prognostic, and therapeutic response tasks. Despite these advances, foundation models are still limited in their ability to encode the entire gigapixel whole-slide images without additional training and often lack complementary multimodal data. Here, we introduce Threads, a slide-level foundation model capable of generating universal representations of whole-slide images of any size. Threads was pre-trained using a multimodal learning approach on a diverse cohort of 47,171 hematoxylin and eosin (H&E)-stained tissue sections, paired with corresponding genomic and transcriptomic profiles - the largest such paired dataset to be used for foundation model development to date. This unique training paradigm enables Threads to capture the tissue's underlying molecular composition, yielding powerful representations applicable to a wide array of downstream tasks. In extensive benchmarking across 54 oncology tasks, including clinical subtyping, grading, mutation prediction, immunohistochemistry status determination, treatment response prediction, and survival prediction, Threads outperformed all baselines while demonstrating remarkable generalizability and label efficiency. It is particularly well suited for predicting rare events, further emphasizing its clinical utility. We intend to make the model publicly available for the broader community.

Large language models (LLMs) have shown impressive capabilities across diverse settings, but still struggle as the length and complexity of the context increases. To address this challenge, we propose Thinking Recursively and Dynamically (ThReaD). THREAD frames model generation as a thread of execution that, based on the context, can run to completion or dynamically spawn new threads. By spawning, threads can offload work (e.g., thinking, retrieving information) to child threads, which only return tokens needed for the parent thread to do its work. In effect, this enables the model to adapt, as needed, the amount of intermediate work used to produce tokens. We apply THREAD in the settings of LLM task solving and question answering, where the dynamic threading allows the model to recursively decompose the given task or question into progressively simpler sub-problems that can be solved by separate child threads. We test THREAD, implemented using a few-shot learning approach, on diverse benchmarks for agent tasks and data-grounded question answering. THREAD achieves state-of-the-art performance with GPT-4 and GPT-3.5 on these benchmarks, including ALFWorld, TextCraft, and WebShop, along with two new benchmarks, DataCommons QA and MIMIC-III ICU QA. In addition, THREAD outperforms existing frameworks by 10% to 50% absolute points with smaller models, including Llama-3-8b and CodeLlama-7b.