Revealing Invisible Cell Phenotypes with Conditional Generative Modeling
Overview
Authors
Affiliations
Biological sciences, drug discovery and medicine rely heavily on cell phenotype perturbation and microscope observation. However, most cellular phenotypic changes are subtle and thus hidden from us by natural cell variability: two cells in the same condition already look different. In this study, we show that conditional generative models can be used to transform an image of cells from any one condition to another, thus canceling cell variability. We visually and quantitatively validate that the principle of synthetic cell perturbation works on discernible cases. We then illustrate its effectiveness in displaying otherwise invisible cell phenotypes triggered by blood cells under parasite infection, or by the presence of a disease-causing pathological mutation in differentiated neurons derived from iPSCs, or by low concentration drug treatments. The proposed approach, easy to use and robust, opens the door to more accessible discovery of biological and disease biomarkers.
Predicting cell morphological responses to perturbations using generative modeling.
Palma A, Theis F, Lotfollahi M Nat Commun. 2025; 16(1):505.
PMID: 39779675 PMC: 11711326. DOI: 10.1038/s41467-024-55707-8.
Exploring self-supervised learning biases for microscopy image representation.
Bendidi I, Bardes A, Cohen E, Lamiable A, Bollot G, Genovesio A Biol Imaging. 2025; 4():e12.
PMID: 39776611 PMC: 11704125. DOI: 10.1017/S2633903X2400014X.
Reprogramming of iPSCs to NPCEC-like cells by biomimetic scaffolds for zonular fiber reconstruction.
Chen T, Chen Z, Du J, Zhang M, Chen Z, Gao Q Bioact Mater. 2024; 45:446-458.
PMID: 39697240 PMC: 11653162. DOI: 10.1016/j.bioactmat.2024.11.031.
Development of AI-assisted microscopy frameworks through realistic simulation with pySTED.
Bilodeau A, Michaud-Gagnon A, Chabbert J, Turcotte B, Heine J, Durand A Nat Mach Intell. 2024; 6(10):1197-1215.
PMID: 39440349 PMC: 11491398. DOI: 10.1038/s42256-024-00903-w.
Towards generative digital twins in biomedical research.
Wu J, Koelzer V Comput Struct Biotechnol J. 2024; 23:3481-3488.
PMID: 39435342 PMC: 11491725. DOI: 10.1016/j.csbj.2024.09.030.