Evaluating the Utilities of Foundation Models in Single‐Cell Data Analysis

Foundation Models (FMs) have made significant strides in both industrial and scientific domains. In this paper, we evaluate the performance of FMs for single‐cell sequencing data analysis through comprehensive experiments across eight downstream tasks pertinent to single‐cell data. Overall, the top FMs include scGPT, Geneformer, and CellFM by considering model performances and user accessibility among ten single‐cell FMs. However, by comparing these FMs with task‐specific methods, we found that single‐cell FMs may not consistently excel than task‐specific methods in all tasks, which challenges the necessity of developing foundation models for single‐cell analysis. In addition, we evaluated the effects of hyperparameters, initial settings, and stability for training single‐cell FMs based on a proposed scEval framework, and provide guidelines for pre‐training and fine‐tuning to enhance the performances of single‐cell FMs. Our work summarizes the current state of single‐cell FMs, points to their constraints and avenues for future development, and offers a freely available evaluation pipeline to benchmark new models and improve method development.