TEDDY: A Family Of Foundation Models For Understanding Single Cell Biology

Understanding the biological mechanism of disease is critical for medicine, and in particular drug discovery. AI-powered analysis of genome-scale biological data hold great potential in this regard. The increasing availability of single-cell RNA sequencing data has enabled the development of large foundation models for disease biology. However, existing foundation models either do not improve or only modestly improve over task-specific models in downstream applications. Here, we explored two avenues for improving the state-of-the-art. First, we scaled the pre-training dataset to 116 million cells, which is larger than those used by previous models. Second, we leveraged the availability of large-scale biological annotations as a form of supervision during pre-training. We trained the TEDDY family of models comprising six transformer-based state-of-the-art single-cell foundation models with 70 million, 160 million, and 400 million parameters. We vetted our models on two downstream evaluation tasks -- identifying the underlying disease state of held-out donors not seen during training and distinguishing healthy cells from diseased ones for disease conditions and donors not seen during training. Scaling experiments showed that performance improved predictably with both data volume and parameter count. Our models showed substantial improvement over existing work on the first task and more muted improvements on the second.

From RAGs to riches: Using large language models to write documents for clinical trials

Clinical trials require numerous documents to be written -- protocols, consent forms, clinical study reports and others. Large language models (LLMs) offer the potential to rapidly generate first versions of these documents, however there are concerns about the quality of their output Here we report an evaluation of LLMs in generating parts of one such document, clinical trial protocols. We find that an offthe-shelf LLM delivers reasonable results, especially when assessing content relevance and the correct use of terminology. However, deficiencies remain: specifically clinical thinking and logic, and appropriate use of references. To improve performance, we used retrieval-augmented generation (RAG) to prompt an LLM with accurate up-to-date information. As a result of using RAG, the writing quality of the LLM improves substantially, which has implications for the practical useability of LLMs in clinical trial-related writing.