RNA-FM: Flow-Matching Generative Model for Genome-wide RNA-Seq Prediction
- URL: http://arxiv.org/abs/2605.11622v1
- Date: Tue, 12 May 2026 06:48:58 GMT
- Title: RNA-FM: Flow-Matching Generative Model for Genome-wide RNA-Seq Prediction
- Abstract summary: We propose RNA-FM, a flow-matching generative framework for genome-wide bulk RNA-seq prediction from whole-slide images.<n> RNA-FM formulates transcriptomic prediction as a continuous-time conditional transport problem.<n>It enables scalable and biologically interpretable genome-wide gene expression imputation.
- Score: 48.07329582311906
- License: http://creativecommons.org/licenses/by-nc-sa/4.0/
- Abstract: Histopathology whole-slide images (WSIs) are routinely acquired in clinical practice and contain rich tissue morphology but lack direct molecular architecture and functional programs defining pathological states, whereas RNA sequencing (RNA-seq) provides genome-wide transcriptional profiles at substantial cost, thereby motivating WSI-based genome-wide transcriptomic prediction. Existing approaches for predicting gene expression from WSIs predominantly rely on deterministic regression with one-to-one mapping, limiting their ability to capture biological heterogeneity and predictive uncertainty. We propose RNA-FM, a flow-matching generative framework for genome-wide bulk RNA-seq prediction from WSIs. RNA-FM formulates transcriptomic prediction as a continuous-time conditional transport problem, learning a velocity field that maps a simple prior to the target gene expression distribution conditioned on morphologies. By integrating pathway-level structure, RNA-FM enables scalable and biologically interpretable genome-wide gene expression imputation. Extensive experiments demonstrate that RNA-FM consistently outperforms state-of-the-art approaches while maintaining biological meaningfulness. Code is available at https://github.com/YXSong000/RNA-FM.
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