A Systematic Evaluation of Single-Cell Foundation Models on Cell-Type Classification Task

This study presents a comprehensive benchmarking of three state-of-the-art single-cell foundation models scGPT, Geneformer, and scFoundation, on cell-type classification tasks. We evaluate the models on three datasets: myeloid, human pancreas, and multiple sclerosis, examining both standard fine-tuning and few-shot learning scenarios. Our work reveals that scFoundation consistently achieves the best performance while Geneformer performs poorly, yielding results sometimes even worse than those of the baseline models. Additionally, we demonstrate that a good foundation model can generalize well even when fine-tuned with out-of-distribution data, a capability that the baseline models lack. Our work highlights the potential of foundation models for addressing challenging biomedical questions, particularly in contexts where models are trained on one population but deployed on another.