ViTally Consistent: Scaling Biological Representation Learning for Cell Microscopy
Keywords: MAE, microscopy, transformers, SSL, linear probing, biology, high-content screening, foundation models
TL;DR: We present a 1.9 billion-parameter ViT-G/8 MAE model that improves linear separability and biological relationship recall in microscopy image analysis.
Abstract: Large-scale cell microscopy screens are used in drug discovery and molecular biology research to study the effects of millions of chemical and genetic perturbations on cells. To use these images in downstream analysis, we need models that can map each image into a feature space that represents diverse biological phenotypes consistently, in the sense that perturbations with similar biological effects have similar representations.
In this work, we present the largest foundation model for cell microscopy data to date, a new 1.9 billion-parameter ViT-G/8 MAE trained on over 8 billion microscopy image crops. Compared to a previous published ViT-L/8 MAE, our new model achieves a 60% improvement in linear separability of genetic perturbations and obtains the best overall performance on whole-genome biological relationship recall and replicate consistency benchmarks. We also show these performance trends hold on a public benchmark for measuring compound activity against target genes.
Beyond scaling, we developed two key methods that improve performance: (1) training on a curated and diverse dataset; and, (2) using biologically motivated linear probing tasks to search across each transformer block for the best candidate representation of whole-genome screens.
We find that many self-supervised vision transformers, pretrained on either natural or microscopy images, yield significantly more biologically meaningful representations of microscopy images in their intermediate blocks than in their typically used final blocks, therefore enabling significant cost and energy savings when deploying these large models in real-world applications. More broadly, our approach and results provide insights toward a general strategy for successfully building foundation models for large-scale biological image data.
Primary Area: applications to physical sciences (physics, chemistry, biology, etc.)
Code Of Ethics: I acknowledge that I and all co-authors of this work have read and commit to adhering to the ICLR Code of Ethics.
Submission Guidelines: I certify that this submission complies with the submission instructions as described on https://iclr.cc/Conferences/2025/AuthorGuide.
Reciprocal Reviewing: I understand the reciprocal reviewing requirement as described on https://iclr.cc/Conferences/2025/CallForPapers. If none of the authors are registered as a reviewer, it may result in a desk rejection at the discretion of the program chairs. To request an exception, please complete this form at https://forms.gle/Huojr6VjkFxiQsUp6.
Anonymous Url: I certify that there is no URL (e.g., github page) that could be used to find authors’ identity.
No Acknowledgement Section: I certify that there is no acknowledgement section in this submission for double blind review.
Submission Number: 12240
Loading