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Updated: Jan 8, 2026

Spatial Profiling of Protein and RNA Expression in Tissue: An Approach to Fine-Tune Virtual Microdissection
Published on: July 6, 2022
Riemannian Metric Learning for Alignment of Spatial Multiomics
Peter Halmos1, Yufan Xia1, Benjamin J Raphael1
1Department of Computer Science, Princeton University, 35 Olden St, Princeton, NJ 08544.
Abstract:
Recent spatial technologies measure the transcriptome, epigenome, proteome, metabolome and other modalities from thousands of cells across a tissue. Most assays typically profile only one modality from a tissue slice, raising the question of how to align spatial data from heterogeneous feature spaces. While multiple approaches have been developed for multi-modal integration of single-cell datasets, few existing techniques perform spatial alignment across arbitrary modalities incorporating both spatial and feature information. We introduce Manifold Gromov-Wasserstein (MGW), a metric-learning framework that exploits the product structure of spatial multiomics to infer modality-specific Riemannian pull-back metrics with neural fields. MGW aligns Riemannian distances induced by these metrics via Gromov-Wasserstein optimal transport, yielding a hyperparameter-free cost across arbitrary modalities sharing a spatial base. The formulation enjoys theoretical invariances - including orthogonal transformations of the spatial and feature domains as well as global feature scalings. We demonstrate the advantages of MGW on multiple alignment tasks, including Stereo-Seq spatiotemporal transcriptomics of mouse embryo, Xenium and Visium spatial transcriptomics of colorectal cancer, and spatial metabolomics-transcriptomics from human striatum and kidney cancer. MGW recovers biologically meaningful correspondences and spatially coherent tissue structures, outperforming existing OT- and non-OT-based multi-modal baselines.
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