The Effect of Preprocessing Choices on Single-Cell Foundation Models
Four scRNA-seq foundation models (scGPT, Geneformer, scFoundation, and scVI) were fine-tuned or trained under alternative denoising, normalization, gene-selection, value-encoding, and neighbor-graph choices. Changing any single step replaced 86% of a cell's nearest neighbors on average and relabeled up to 9% of held-out cells in cell-type prediction, with rare populations disproportionately affected; mismatched preprocessing between fine-tuning and inference could drop accuracy to chance.
Venue: NeurIPS 2026 Workshop on I Can't Believe It's Not Better: Failure Modes of AI in Biology (ICBINB)
Rich J, Pachter L. (2026). "The Effect of Preprocessing Choices on Single-Cell Foundation Models." NeurIPS 2026 Workshop on I Can't Believe It's Not Better: Failure Modes of AI in Biology (ICBINB).