# MoLF: Mixture-of-Latent-Flow for Pan-Cancer Spatial Gene Expression Prediction from Histology

arXiv: https://arxiv.org/abs/2602.02282 · HTML: https://mlsanity.com/paper/2602.02282/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Placed in Medical and biomedical MoE, one of 12 directions in Mixture-of-experts.
- Builds on 8 of its 22 references that are in the map.
- First posted on arXiv 2 Feb 2026.

## Placed in

- Mixture-of-experts / [Medical and biomedical MoE](https://mlsanity.com/moe/medical-and-biomedical-moe/)

## Builds on (most cited first, 8 of 8)

- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Switch Transformers: Scaling to Trillion Parameter Models with Simple and Efficient Sparsity](https://mlsanity.com/paper/2101.03961/) (2021)
- [An Introduction to Variational Autoencoders](https://mlsanity.com/paper/1906.02691/) (2019)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [Accurate Spatial Gene Expression Prediction by integrating Multi-resolution features](https://mlsanity.com/paper/2403.07592/) (2024)
- [Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images](https://mlsanity.com/paper/2501.15598/) (2025)
- [Scalable Generation of Spatial Transcriptomics from Histology Images via Whole-Slide Flow Matching](https://mlsanity.com/paper/2506.05361/) (2025)

## Abstract (arXiv)

Inferring spatial transcriptomics (ST) from histology enables scalable histogenomic profiling, yet current methods are largely restricted to single-tissue models. This fragmentation fails to leverage biological principles shared across cancer types and hinders application to data-scarce scenarios. While pan-cancer training offers a solution, the resulting heterogeneity challenges monolithic architectures. To bridge this gap, we introduce MoLF (Mixture-of-Latent-Flow), a generative model for pan-cancer histogenomic prediction. MoLF leverages a conditional Flow Matching objective to map noise to the gene latent manifold, parameterized by a Mixture-of-Experts (MoE) velocity field. By dynamically routing inputs to specialized sub-networks, this architecture effectively decouples the optimization of diverse tissue patterns. Our experiments demonstrate that MoLF establishes a new state-of-the-art, consistently outperforming both specialized and foundation model baselines on pan-cancer benchmarks. Furthermore, MoLF exhibits zero-shot generalization to cross-species data, suggesting it captures fundamental, conserved histo-molecular mechanisms.
