Cell-DINO: Self-supervised image-based embeddings for cell fluorescent microscopy

Accurately quantifying cellular morphology at scale could substantially empower existing single-cell approaches. However, measuring cell morphology remains an active field of research, which has inspired multiple computer vision algorithms over the years. Here, we show that DINOv2, a vision-transformer based, self-supervised algorithm, has a remarkable ability for learning rich representations of cellular morphology without manual annotations or any other type of supervision. We apply DINOv2 to cell phenotyping problems, and compare the performance of resulting models, called Cell-DINO models, on a wide variety of tasks across two publicly available imaging datasets of diverse specifications and biological focus. Compared to supervised and other self-supervised baselines, Cell-DINO models demonstrate improved performance, especially in low annotation regimes. For instance, to classify protein localization using only 1% of annotations on a challenging single-cell dataset, Cell-DINO performs 70% better than a supervised strategy, and 24% better than another self-supervised alternative. The results show that Cell-DINO can support the study of unknown biological variation, including single-cell heterogeneity and relationships between experimental conditions, making it an excellent tool for image-based biological discovery.