# CellPainTR: Generalizable Representation Learning for Cross-Dataset Cell Painting Analysis

arXiv: https://arxiv.org/abs/2509.06986 · HTML: https://mlsanity.com/paper/2509.06986/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 7 of its 22 references that are in the map.
- First posted on arXiv 2 Sep 2025.

## Builds on (most cited first, 7 of 7)

- [Attention Is All You Need](https://mlsanity.com/paper/1706.03762/) (2017)
- [BERT: Pre-training of Deep Bidirectional Transformers for Language Understanding](https://mlsanity.com/paper/1810.04805/) (2018)
- [A Simple Framework for Contrastive Learning of Visual Representations](https://mlsanity.com/paper/2002.05709/) (2020)
- [Hyena Hierarchy: Towards Larger Convolutional Language Models](https://mlsanity.com/paper/2302.10866/) (2023)
- [From Louvain to Leiden: guaranteeing well-connected communities](https://mlsanity.com/paper/1810.08473/) (2018)
- [Masked Autoencoders for Microscopy are Scalable Learners of Cellular Biology](https://mlsanity.com/paper/2404.10242/) (2024)
- [scHyena: Foundation Model for Full-Length Single-Cell RNA-Seq Analysis in Brain](https://mlsanity.com/paper/2310.02713/) (2023)

## Abstract (arXiv)

Large-scale biological discovery requires integrating massive, heterogeneous datasets like those from the JUMP Cell Painting consortium, but technical batch effects and a lack of generalizable models remain critical roadblocks. To address this, we introduce CellPainTR, a Transformer-based architecture designed to learn foundational representations of cellular morphology that are robust to batch effects. Unlike traditional methods that require retraining on new data, CellPainTR's design, featuring source-specific context tokens, allows for effective out-of-distribution (OOD) generalization to entirely unseen datasets without fine-tuning. We validate CellPainTR on the large-scale JUMP dataset, where it outperforms established methods like ComBat and Harmony in both batch integration and biological signal preservation. Critically, we demonstrate its robustness through a challenging OOD task on the unseen Bray et al. dataset, where it maintains high performance despite significant domain and feature shifts. Our work represents a significant step towards creating truly foundational models for image-based profiling, enabling more reliable and scalable cross-study biological analysis.