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CellFlux: Simulating Cellular Morphology Changes via Flow Matching

Yuhui Zhang, Yuchang Su, Chenyu Wang, Tianhong Li, Zoe Wefers, Jeffrey J. Nirschl, James Burgess, Daisy Ding, Alejandro Lozano, Emma Lundberg, Serena Yeung-Levy

2025Year
2Top-tier citations

Abstract

Building a virtual cell capable of accurately simulating cellular behaviors in silico has long been a dream in computational biology. We introduce CellFlux, an image-generative model that simulates cellular morphology changes induced by chemical and genetic perturbations using flow matching. Unlike prior methods, CellFlux models distribution-wise transformations from unperturbed to perturbed cell states, effectively distinguishing actual perturbation effects from experimental artifacts such as batch effects-a major challenge in biological data. Evaluated on chemical (BBBC021), genetic (RxRx1), and combined perturbation (JUMP) datasets, CellFlux generates biologically meaningful cell images that faithfully capture perturbation-specific morphological changes, achieving a 35% improvement in FID scores and a 12% increase in mode-ofaction prediction accuracy over existing methods. Additionally, CellFlux enables continuous interpolation between cellular states, providing a potential tool for studying perturbation dynamics. These capabilities mark a significant step toward realizing virtual cell modeling for biomedical research. Project page: https://yuhui-zh15. github.io/CellFlux/ .

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