# Latent Gene Diffusion for Spatial Transcriptomics Completion

arXiv: https://arxiv.org/abs/2509.01864 · HTML: https://mlsanity.com/paper/2509.01864/

## Key facts

- Cited by 1 papers in the map (data through 14 Oct 2026).
- Builds on 11 of its 33 references that are in the map.
- First posted on arXiv 2 Sep 2025.

## Builds on (most cited first, 11 of 11)

- [Adam: A Method for Stochastic Optimization](https://mlsanity.com/paper/1412.6980/) (2014)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [High-Resolution Image Synthesis with Latent Diffusion Models](https://mlsanity.com/paper/2112.10752/) (2021)
- [Scalable Diffusion Models with Transformers](https://mlsanity.com/paper/2212.09748/) (2022)
- [Machine learning methods for histopathological image analysis](https://mlsanity.com/paper/1709.00786/) (2017)
- [Spatially Resolved Gene Expression Prediction from H&E Histology Images via Bi-modal Contrastive Learning](https://mlsanity.com/paper/2306.01859/) (2023)
- [Exemplar Guided Deep Neural Network for Spatial Transcriptomics Analysis of Gene Expression Prediction](https://mlsanity.com/paper/2210.16721/) (2022)
- [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)
- [SEPAL: Spatial Gene Expression Prediction from Local Graphs](https://mlsanity.com/paper/2309.01036/) (2023)
- [Emerging Artificial Intelligence Applications in Spatial Transcriptomics Analysis](https://mlsanity.com/paper/2203.09664/) (2022)

## Built on by (most cited first, 1 of 1)

- [Hyperbolic Contrastive Learning with Entailment for Spatial Transcriptomics](https://mlsanity.com/paper/2609.16207/) (2026)

## Abstract (arXiv)

Computer Vision has proven to be a powerful tool for analyzing Spatial Transcriptomics (ST) data. However, current models that predict spatially resolved gene expression from histopathology images suffer from significant limitations due to data dropout. Most existing approaches rely on single-cell RNA sequencing references, making them dependent on alignment quality and external datasets while also risking batch effects and inherited dropout. In this paper, we address these limitations by introducing LGDiST, the first reference-free latent gene diffusion model for ST data dropout. We show that LGDiST outperforms the previous state-of-the-art in gene expression completion, with an average Mean Squared Error that is 18% lower across 26 datasets. Furthermore, we demonstrate that completing ST data with LGDiST improves gene expression prediction performance on six state-of-the-art methods up to 10% in MSE. A key innovation of LGDiST is using context genes previously considered uninformative to build a rich and biologically meaningful genetic latent space. Our experiments show that removing key components of LGDiST, such as the context genes, the ST latent space, and the neighbor conditioning, leads to considerable drops in performance. These findings underscore that the full architecture of LGDiST achieves substantially better performance than any of its isolated components.