# STP-BENCH: A Unified Systematic Benchmark for Virtual Spatial Transcriptomics from Histopathology Images

arXiv: https://arxiv.org/abs/2609.05956 · HTML: https://mlsanity.com/paper/2609.05956/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 103 references that are in the map.
- First posted on arXiv 5 Sep 2026.

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

- [An Image is Worth 16x16 Words: Transformers for Image Recognition at Scale](https://mlsanity.com/paper/2010.11929/) (2020)
- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Flow Matching for Generative Modeling](https://mlsanity.com/paper/2210.02747/) (2022)
- [Orca: Progressive Learning from Complex Explanation Traces of GPT-4](https://mlsanity.com/paper/2306.02707/) (2023)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [Virchow: A Million-Slide Digital Pathology Foundation Model](https://mlsanity.com/paper/2309.07778/) (2023)
- [Accelerating Data Processing and Benchmarking of AI Models for Pathology](https://mlsanity.com/paper/2502.06750/) (2025)
- [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)
- [M2ORT: Many-To-One Regression Transformer for Spatial Transcriptomics Prediction from Histopathology Images](https://mlsanity.com/paper/2401.10608/) (2024)
- [AI-driven 3D Spatial Transcriptomics](https://mlsanity.com/paper/2502.17761/) (2025)

## Abstract (arXiv)

Spatial transcriptomics (ST) provides unprecedented insights into tumor heterogeneity by capturing spatially resolved gene expression, yet its high experimental cost hinders large-scale adoption. Consequently, computational approaches that predict spatial gene expression directly from hematoxylin and eosin slides, termed virtual ST, have rapidly emerged. Despite this progress, assessing advances in the field remains difficult due to insufficient benchmarking: prior studies rely on small, heterogeneous datasets, inconsistent training and inference pipelines, and limited evaluation of biological interpretability and model robustness. To address these gaps, we present STP-BENCH, a standardized benchmark for virtual ST models. STP-BENCH comprises six cancer types spanning two ST platforms (Visium and Xenium), with each training dataset containing more than 30,000 spots and at least 15 slides to ensure statistical reliability. We evaluate 21 predictive approaches, re-implemented with a unified pathology foundation model as the morphological encoder when architecturally applicable. Beyond conventional benchmarks that report average predictive accuracy on highly variable genes, we systematically examine which genes and gene sets are recoverable from histomorphology. We further evaluate the downstream biological utility of predicted profiles through cell-type deconvolution and spatial domain identification, and assess model reliability under domain shifts and data scaling. Notably, unified morphological encoding substantially re-orders model rankings established in prior studies, indicating that architectural innovations and image encoding have been conflated in previous evaluations. We publicly release STP-BENCH to support reproducibility and serve as a community benchmark at https://github.com/NEXGEM/STP-Bench.