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Spatial integration of multi-omics single-cell data with SIMO

Author

Listed:
  • Penghui Yang

    (Zhejiang University
    Zhejiang University)

  • Kaiyu Jin

    (Zhejiang University)

  • Yue Yao

    (Zhejiang University)

  • Lijun Jin

    (Zhejiang University
    Zhejiang University)

  • Xin Shao

    (Zhejiang University
    Zhejiang University)

  • Chengyu Li

    (Zhejiang University
    Zhejiang University)

  • Xiaoyan Lu

    (Zhejiang University
    Zhejiang University)

  • Xiaohui Fan

    (Zhejiang University
    Zhejiang University
    Ningbo Municipal Hospital of TCM
    Shaoxing University)

Abstract

Technical limitations in spatial and single-cell omics sequencing pose challenges for capturing and describing multimodal information at the spatial scale. To address this, we develop SIMO, a computational method designed for the Spatial Integration of Multi-Omics datasets through probabilistic alignment. Unlike previous tools, SIMO not only integrates spatial transcriptomics with single-cell RNA-seq but expands beyond, enabling integration across multiple single-cell modalities, such as chromatin accessibility and DNA methylation, which have not been co-profiled spatially before. We benchmark SIMO on simulated datasets, demonstrating its high accuracy and robustness. Further application on biological datasets reveals SIMO’s ability to detect topological patterns of cells and their regulatory modes across multiple omics layers. Through comprehensive analysis of real-world data, SIMO uncovers multimodal spatial heterogeneity, offering deeper insights into the spatial organization and regulation of biological molecules. These findings position SIMO as a powerful tool for advancing spatial biology by revealing previously inaccessible multimodal insights.

Suggested Citation

  • Penghui Yang & Kaiyu Jin & Yue Yao & Lijun Jin & Xin Shao & Chengyu Li & Xiaoyan Lu & Xiaohui Fan, 2025. "Spatial integration of multi-omics single-cell data with SIMO," Nature Communications, Nature, vol. 16(1), pages 1-15, December.
  • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-56523-4
    DOI: 10.1038/s41467-025-56523-4
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    References listed on IDEAS

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    1. Christoph Kuppe & Ricardo O. Ramirez Flores & Zhijian Li & Sikander Hayat & Rebecca T. Levinson & Xian Liao & Monica T. Hannani & Jovan Tanevski & Florian Wünnemann & James S. Nagai & Maurice Halder &, 2022. "Spatial multi-omic map of human myocardial infarction," Nature, Nature, vol. 608(7924), pages 766-777, August.
    2. Christian F. Guerrero-Juarez & Priya H. Dedhia & Suoqin Jin & Rolando Ruiz-Vega & Dennis Ma & Yuchen Liu & Kosuke Yamaga & Olga Shestova & Denise L. Gay & Zaixin Yang & Kai Kessenbrock & Qing Nie & Wa, 2019. "Single-cell analysis reveals fibroblast heterogeneity and myeloid-derived adipocyte progenitors in murine skin wounds," Nature Communications, Nature, vol. 10(1), pages 1-17, December.
    3. Jeffrey M. Perkel, 2021. "Single-cell analysis enters the multiomics age," Nature, Nature, vol. 595(7868), pages 614-616, July.
    4. Zhuzhu Zhang & Jingtian Zhou & Pengcheng Tan & Yan Pang & Angeline C. Rivkin & Megan A. Kirchgessner & Elora Williams & Cheng-Ta Lee & Hanqing Liu & Alexis D. Franklin & Paula Assakura Miyazaki & Anna, 2021. "Epigenomic diversity of cortical projection neurons in the mouse brain," Nature, Nature, vol. 598(7879), pages 167-173, October.
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