# RNA-FM: Flow-Matching Generative Model for Genome-wide RNA-Seq Prediction

arXiv: https://arxiv.org/abs/2605.11622 · HTML: https://mlsanity.com/paper/2605.11622/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical imaging and segmentation, one of 14 directions in Diffusion models.
- Builds on 16 of its 37 references that are in the map.
- First posted on arXiv 12 May 2026.

## Placed in

- Diffusion models / [Medical imaging and segmentation](https://mlsanity.com/diffusion/medical-imaging-and-segmentation/)

## Builds on (most cited first, 16 of 16)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Score-Based Generative Modeling through Stochastic Differential Equations](https://mlsanity.com/paper/2011.13456/) (2020)
- [Classifier-Free Diffusion Guidance](https://mlsanity.com/paper/2207.12598/) (2022)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Improved Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2102.09672/) (2021)
- [Artificial Intelligence for Digital and Computational Pathology](https://mlsanity.com/paper/2401.06148/) (2023)
- [Modeling Dense Multimodal Interactions Between Biological Pathways and Histology for Survival Prediction](https://mlsanity.com/paper/2304.06819/) (2023)
- [Histopathology Whole Slide Image Analysis with Heterogeneous Graph Representation Learning](https://mlsanity.com/paper/2307.04189/) (2023)
- [Multimodal Prototyping for cancer survival prediction](https://mlsanity.com/paper/2407.00224/) (2024)
- [Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images](https://mlsanity.com/paper/2501.15598/) (2025)
- [scDiffusion: conditional generation of high-quality single-cell data using diffusion model](https://mlsanity.com/paper/2401.03968/) (2024)
- [Learning to Predict RNA Sequence Expressions from Whole Slide Images with Applications for Search and Classification](https://mlsanity.com/paper/2203.13997/) (2022)
- [IDF: Iterative Dynamic Filtering Networks for Generalizable Image Denoising](https://mlsanity.com/paper/2508.19649/) (2025)
- [Taming Camera-Controlled Video Generation with Verifiable Geometry Reward](https://mlsanity.com/paper/2512.02870/) (2025)
- [MIRROR: Multi-Modal Pathological Self-Supervised Representation Learning via Modality Alignment and Retention](https://mlsanity.com/paper/2503.00374/) (2025)
- [Gene-DML: Dual-Pathway Multi-Level Discrimination for Gene Expression Prediction from Histopathology Images](https://mlsanity.com/paper/2507.14670/) (2025)

## Abstract (arXiv)

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.