PETRI: Learning Unified Cell Embeddings from Unpaired Modalities via Early-Fusion Joint Reconstruction

Ryan Conrad, Ethan Weinberger, Saradha Venkatachalapathy, Yuwen Chen, Darshini Shah, Bay Johnson, Max Salick, Vaishaali Natarajan, Emily Fox

International Conference on Learning Representations 2026 (ICLR 2026) Conference

Integrating imaging and transcriptomics screening data holds promise for isolating true biological signals from modality-specific technical artifacts. However, existing multimodal embedding approaches either require pairing or fail to capture both shared and modality-specific information in an end-to-end manner. We present PETRI, an early-fusion transformer that learns a unified cell embedding from unpaired cellular images and gene expression profiles. PETRI groups cells by shared experimental context into multimodal “documents” and performs masked joint reconstruction with cross-modal attention, permitting information sharing while preserving modality-specific capacity. The resulting latent space supports construction of perturbation-level profiles by simple averaging across modalities. Applying sparse autoencoders to the embeddings reveals learned concepts that are biologically meaningful, multimodal, and retain perturbation-specific effects. To support further machine learning research, we release a blinded, matched optical pooled screen (OPS) and Perturb-seq dataset in HepG2 cells.