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.

Controllable Mixed-Initiative Dialogue Generation through Prompting

Mixed-initiative dialogue tasks involve repeated exchanges of information and conversational control. Conversational agents gain control by generating responses that follow particular dialogue intents or strategies, prescribed by a policy planner. The standard approach has been fine-tuning pre-trained language models to perform generation conditioned on these intents. However, these supervised generation models are limited by the cost and quality of data annotation. We instead prompt large language models as a drop-in replacement to fine-tuning on conditional generation. We formalize prompt construction for controllable mixed-initiative dialogue. Our findings show improvements over fine-tuning and ground truth responses according to human evaluation and automatic metrics for two tasks: PersuasionForGood and Emotional Support Conversations.