Aug 2026· Nature· Vol 657, pp. 744 - 754· 4 citations· 62 references
Medicine
TL;DR
VirTues-derived biomarkers predict anti-PD-L1 chemo-immunotherapy response and stratify disease-free survival in an independent cohort, outperforming state-of-the-art biomarkers derived from the same datasets and current clinical stratification schemes.
Abstract
Spatial proteomics technologies have transformed our understanding of complex tissue architecture in cancer but present unique challenges for computational analysis1. Each study uses a different marker panel and protocol, and most methods are tailored to single cohorts, which limits knowledge transfer and robust biomarker discovery. Here we present Virtual Tissues (VirTues), a general-purpose foundation model for spatial proteomics that learns marker-aware, multi-scale representations of proteins, cells, niches and tissues directly from multiplex imaging data. From a single pretrained backbone, VirTues supports marker reconstruction, cell segmentation and typing, niche annotation, spatial biomarker discovery and patient stratification, including zero-shot annotation across heterogeneous panels and datasets. In triple-negative breast cancer, VirTues-derived biomarkers predict anti-PD-L1 chemo-immunotherapy response2 and stratify disease-free survival in an independent cohort3, outperforming state-of-the-art biomarkers derived from the same datasets and current clinical stratification schemes. Virtual Tissues (VirTues), a foundation model for spatial proteomics that captures tissue organization across scales, supports marker reconstruction, cell segmentation and typing, niche annotation, spatial biomarker discovery and patient stratification across heterogeneous panels and datasets.
Spatial transcriptomics now profiles patient cohorts at single-cell resolution, enabling analysis of disease-associated cell organization in situ. However, discovering such spatial biomarkers remains challenging because relevant structures occur at unknown scales and cell-or niche-level annotations are rarely available...
Hoeyoung Kim, Donghee Kim, Sangwook Jung et al.· bioRxiv· 0 citations
X-SPATIO is a spatially compatible computational pipeline designed to directly link hematoxylin and eosin morphology with region-matched mRNA and protein expression, enabling cost-effective inference of spatial biomarker expression and establishing a foundation for biologically grounded discovery and precision oncology...
Vibha R. Rao, Madhumala K. Sadanandappa, C. Black et al.· American Journal of Patholog...· 0 citations
SPgen integrates protein sequences, functional annotations, transcriptomic profiles, and spatial information to learn transferable representations that enable inference beyond experimentally profiled proteins, and accurately reconstructs measured spatial patterns, reduces measurement noise, and enables proteome-wide sp...
Jia-Chen Li, Kai-Yuan Yang, Qiaoling Che et al.· bioRxiv· 0 citations
Spatial transcriptomics reveals cellular heterogeneity, intercellular communication, and tissue organization, but its cost and limited accessibility restrict clinical use. Here, we present VISTA, a model that integrates multi-scale histological features and spatial context to infer spatial gene expression from H&E-stai...
Shaoqing Jiao, Zhen Yuan, Dazhi Lu et al.· bioRxiv· 0 citations
Novel imaging methods that may extend 2D spatial analyses into 3D modelling, and the complementary applicability of deep-learning-based computational pathology are discussed, as well as the advantages, limitations and applications of spatial omics technologies in kidney research.
Takahisa Yoshikawa, R. D. Bülow, P. Boor et al.· Nature Reviews Nephrology· 1 citation
Spatial omics (SO) technologies enable spatially resolved molecular profiling, while hematoxylin and eosin (H&E) imaging remains the gold standard for morphological assessment in clinical pathology. Recent computational advances increasingly place H&E images at the center of SO analysis, bridging morphology with transc...
Ning-Hui Hao, Bo-Shen Yan, Dong Li et al.· Proceedings of the 32nd ACM...· 0 citations
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