# SPATIA: Multimodal Generation and Prediction of Spatial Cell Phenotypes

arXiv: https://arxiv.org/abs/2507.04704 · HTML: https://mlsanity.com/paper/2507.04704/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 21 of its 77 references that are in the map.
- First posted on arXiv 7 Jul 2025.

## Builds on (most cited first, 21 of 21)

- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
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- [Sinkhorn Distances: Lightspeed Computation of Optimal Transportation Distances](https://mlsanity.com/paper/1306.0895/) (2013)
- [Demystifying MMD GANs](https://mlsanity.com/paper/1801.01401/) (2018)
- [Improving and generalizing flow-based generative models with minibatch optimal transport](https://mlsanity.com/paper/2302.00482/) (2023)
- [Scaling Vision Transformers to Gigapixel Images via Hierarchical Self-Supervised Learning](https://mlsanity.com/paper/2206.02647/) (2022)
- [Multimodal Whole Slide Foundation Model for Pathology](https://mlsanity.com/paper/2411.19666/) (2024)
- [Visual Language Pretrained Multiple Instance Zero-Shot Transfer for Histopathology Images](https://mlsanity.com/paper/2306.07831/) (2023)
- [HEST-1k: A Dataset for Spatial Transcriptomics and Histology Image Analysis](https://mlsanity.com/paper/2406.16192/) (2024)
- [Hibou: A Family of Foundational Vision Transformers for Pathology](https://mlsanity.com/paper/2406.05074/) (2024)
- [Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Images](https://mlsanity.com/paper/2501.15598/) (2025)
- [Multimodal contrastive learning for spatial gene expression prediction using histology images](https://mlsanity.com/paper/2407.08216/) (2024)
- [STimage-1K4M: A histopathology image-gene expression dataset for spatial transcriptomics](https://mlsanity.com/paper/2406.06393/) (2024)
- [CellFlux: Simulating Cellular Morphology Changes via Flow Matching](https://mlsanity.com/paper/2502.09775/) (2025)
- [Scalable Generation of Spatial Transcriptomics from Histology Images via Whole-Slide Flow Matching](https://mlsanity.com/paper/2506.05361/) (2025)
- [xTrimoGene: An Efficient and Scalable Representation Learner for Single-Cell RNA-Seq Data](https://mlsanity.com/paper/2311.15156/) (2023)
- [ST-Align: A Multimodal Foundation Model for Image-Gene Alignment in Spatial Transcriptomics](https://mlsanity.com/paper/2411.16793/) (2024)
- [scHyena: Foundation Model for Full-Length Single-Cell RNA-Seq Analysis in Brain](https://mlsanity.com/paper/2310.02713/) (2023)
- [scInterpreter: Training Large Language Models to Interpret scRNA-seq Data for Cell Type Annotation](https://mlsanity.com/paper/2402.12405/) (2024)

## Abstract (arXiv)

Understanding how cellular morphology, gene expression, and spatial context jointly shape tissue function is a central challenge in biology. Image-based spatial transcriptomics technologies now provide high-resolution measurements of cell images and gene expression profiles, but existing methods typically analyze these modalities in isolation or at limited resolution. We address the problem by introducing SPATIA, a multi-level generative and predictive model that learns unified, spatially aware representations by fusing morphology, gene expression, and spatial context from the cell to the tissue level. SPATIA also incorporates a spatially conditioned generative framework with confidence-aware OT reweighting and morphology-profile alignment for modeling target-state morphology distributions. Specifically, we propose a confidence-aware flow matching objective that reweights weak optimal-transport pairs based on uncertainty. We further apply morphology-profile alignment to encourage biologically meaningful image generation, enabling the modeling of microenvironment-dependent phenotypic transitions. We assembled a multi-scale dataset consisting of 25.9 million cell-gene pairs across 17 tissues. We benchmark SPATIA against 18 models across 12 tasks, spanning categories such as phenotype generation, annotation, clustering, gene imputation, and cross-modal prediction. SPATIA achieves improved performance over state-of-the-art models, improving generative fidelity by 8% and predictive accuracy by up to 3%.