# Spatial Transcriptomics-Guided Alignment Enhances Molecular Profiling in Pathology Foundation Model

arXiv: https://arxiv.org/abs/2606.03644 · HTML: https://mlsanity.com/paper/2606.03644/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 6 of its 65 references that are in the map.
- First posted on arXiv 29 May 2026.

## Builds on (most cited first, 6 of 6)

- [DINOv2: Learning Robust Visual Features without Supervision](https://mlsanity.com/paper/2304.07193/) (2023)
- [Representation Learning with Contrastive Predictive Coding](https://mlsanity.com/paper/1807.03748/) (2018)
- [CoCa: Contrastive Captioners are Image-Text Foundation Models](https://mlsanity.com/paper/2205.01917/) (2022)
- [Parameter-Efficient Fine-Tuning for Large Models: A Comprehensive Survey](https://mlsanity.com/paper/2403.14608/) (2024)
- [Virchow2: Scaling Self-Supervised Mixed Magnification Models in Pathology](https://mlsanity.com/paper/2408.00738/) (2024)
- [PathBench: A comprehensive comparison benchmark for pathology foundation models towards precision oncology](https://mlsanity.com/paper/2505.20202/) (2025)

## Abstract (arXiv)

Comprehensive molecular profiling is essential for modern precision oncology but remains hindered by prohibitive costs, specimen exhaustion, and protracted turnaround times. While pathology foundation models (PFMs) have demonstrated potential for inferring molecular phenotypes from routine hematoxylin and eosin (H&E) whole-slide images (WSIs), current architectures primarily rely on vision-centric self-supervised learning or vision-language alignment, lacking the spatially resolved molecular supervision required to connect subtle morphological features with underlying genomic alterations. Spatial transcriptomics (ST) emerges as a transformative technology that enables transcriptomic quantification within intact tissue sections, thereby preserving the precise spatial link between histology and molecular profiles. In this study, we present a Spatial Transcriptomics-guided Alignment framework for Molecular Profiling (STAMP), which endows PFMs with intrinsic molecular awareness. To support this paradigm, we curated HumanST-1k, a human ST dataset spanning diverse anatomical organs and sequencing platforms. This atlas yields 1.8 million pairs of H&E patches and corresponding transcriptomic profiles, providing a corpus that links histological structures with their molecular states. To mitigate the technical noise inherent to raw transcriptomics, STAMP applies a pathway-informed alignment strategy that aggregates transcriptomic data into biologically functional pathways, which are subsequently integrated into PFMs via parameter-efficient fine-tuning. This alignment enriches the representation space of PFMs and unlocks their capacity to resolve sub-visual molecular signatures. The clinical utility of these augmented representations was validated through a multi-tier evaluation framework.