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This paper introduces FACET, a generative framework that leverages factorized asymmetric conditioning to synthesize high-fidelity fluorescence microscopy images from protein sequences and cellular context. By explicitly separating spatial morphological cues from non-spatial sequence semantics, the method achieves significant improvements in spatial overlap and image fidelity while reducing computational overhead. This approach advances the field of scientific machine learning by enabling more efficient *in silico* localization of unimaged proteins within complex cellular environments.
FACET: Factorized Asymmetric Conditioning for Efficient Transport in High-Fidelity Fluorescence Microscopy Synthesis
arXiv:2610.05353v1 Announce Type: new Abstract: Fluorescence microscopy reveals where proteins localize, but only a limited number of proteins can be imaged in the same cell; generating these images from amino-acid sequence and the cell's morphological context enables in silico localization of unimaged proteins. The two conditions, however, play asymmetric roles: morphological context is spatially aligned with the target, whereas sequence is non-spatial and must specify protein-dependent localization within it, with recurring coarse patterns shared across proteins and finer protein-specific variation. Existing generators condition on both jointly, without separating what each explains. We introduce FACET (Factorized Asymmetric Conditioning for Efficient Transport), a probabilistic generative framework that encodes this structure as an explicit inductive bias: sequence semantics are learned from what context leaves unexplained, coarse localization regularities are shared across proteins through a semantic memory, and protein-specific variation is a bounded residual around them. A variance-preserving state projection further lets FACET perform continuous stochastic transport through a pretrained diffusion predictor with minimal parameter overhead. On held-out proteins, FACET improves spatial overlap by 34.3% on the Human Protein Atlas and 14.0% on OpenCell over a backbone-matched baseline, and reduces FID by 27.2% and 46.5%, respectively, with 75% fewer network evaluations. It also substantially improves protein-association structure recovery and yields better-calibrated predictions, while detailed ablations show complementary contributions from its design choices. These results identify factorized asymmetric conditioning, rather than generator capacity alone, as a key lever for high-fidelity, efficient, and biologically meaningful cellular image synthesis.
Abstract:Fluorescence microscopy reveals where proteins localize, but only a limited number of proteins can be imaged in the same cell; generating these images from amino-acid sequence and the cell's morphological context enables in silico localization of unimaged proteins. The two conditions, however, play asymmetric roles: morphological context is spatially aligned with the target, whereas sequence is non-spatial and must specify protein-dependent localization within it, with recurring coarse patterns shared across proteins and finer protein-specific variation. Existing generators condition on both jointly, without separating what each explains. We introduce FACET (Factorized Asymmetric Conditioning for Efficient Transport), a probabilistic generative framework that encodes this structure as an explicit inductive bias: sequence semantics are learned from what context leaves unexplained, coarse localization regularities are shared across proteins through a semantic memory, and protein-specific variation is a bounded residual around them. A variance-preserving state projection further lets FACET perform continuous stochastic transport through a pretrained diffusion predictor with minimal parameter overhead. On held-out proteins, FACET improves spatial overlap by 34.3% on the Human Protein Atlas and 14.0% on OpenCell over a backbone-matched baseline, and reduces FID by 27.2% and 46.5%, respectively, with 75% fewer network evaluations. It also substantially improves protein-association structure recovery and yields better-calibrated predictions, while detailed ablations show complementary contributions from its design choices. These results identify factorized asymmetric conditioning, rather than generator capacity alone, as a key lever for high-fidelity, efficient, and biologically meaningful cellular image synthesis.
Machine Learning (cs.LG); Computer Vision and Pattern Recognition (cs.CV)
arXiv:2610.05353 [cs.LG]
(or arXiv:2610.05353v1 [cs.LG] for this version)
https://doi.org/10.48550/arXiv.2610.05353 Focus to learn more arXiv-issued DOI via DataCite (pending registration)
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