ARISE: RNA-Anchored Shared-Edge Topology and Hierarchical Fusion for Spatial Multi-Omics Integration
Xiangxiang Wang, Yanchi Su, Gaoyang Hao, Meng Wang, Yunhe Wang, Xiangtao LiAbstract
Motivation
Spatial multi-omics technologies jointly profile transcriptomes, proteins and chromatin accessibility in situ, enabling integrative analysis of tissue organization across molecular layers. However, most existing graph-based integration methods rely on independently constructed modality-specific k-nearest-neighbor graphs. When auxiliary modalities are sparse or noisy, these graphs can become topologically discordant, propagate spurious edges, weaken cross-modal alignment and reduce spatial domain resolution.
Results
We present ARISE (Anchored RNA for Integrated Spatial Embedding), an RNA expression anchored framework for spatial multi-omics integration. ARISE defines a shared-edge topology by intersecting RNA feature-similarity and spatial-proximity graphs, encodes auxiliary modalities on this common scaffold, and integrates them through inside-out hierarchical fusion. We further show theoretically that graph intersection minimizes false-positive edges within a broad class of k-of-r graph fusion rules, providing a principled basis for topology anchoring. Across various spatial multi-omics benchmarks spanning simulated and real datasets in bi-modal and tri-modal settings, ARISE improves spatial domain identification, cross-modal consistency and preservation of tissue structure relative to existing methods. Furthermore, the learned representation supports biologically meaningful downstream analyses, including marker-based domain annotation, pathway enrichment and cis-regulatory inference, indicating that ARISE yields a robust and interpretable framework for spatial multi-omics integration.
Availability
The source code is available at https://github.com/XiangxiangWang-code/ARISE. The archived version used in this study is available at https://doi.org/10.6084/m9.figshare.32686137.v2.