MorphoCLIP: Text-Supervised Contrastive Learning for Perturbation Matching in Cell Painting Images

Abstract

Cell Painting microscopy captures how cells change after a chemical or genetic perturbation. Connecting these images to the perturbations that produced them could make large imaging screens easier to search and interpret, but the task remains difficult because biological effects are subtle and technical variation is substantial. We introduce MorphoCLIP, a contrastive model that links Cell Painting profiles with text descriptions of compounds, CRISPR knockouts, and ORF overexpressions. The model keeps its vision and language backbones frozen and trains only a compact cross-channel module and projection layers, so it can be trained on a single consumer GPU. On held-out CPJUMP1 data, MorphoCLIP searches in both directions: from a cell image to its perturbation description and from a description to matching cell images. In both cases, a correct match appears among the top ten results much more often than expected by chance. Adding a replicate-alignment loss makes profiles from repeated experiments more consistent, although this improvement does not yet translate into reliable gene-compound matching. Gene-aware labels and plate correction also show no consistent retrieval benefit. These findings suggest that text supervision can help organize chemical and genetic Cell Painting data. Matching compounds with genetic perturbations, however, remains an open problem.