{
  "abstract": "Nearby cells within tissues communicate through ligand-receptor signaling interactions. Emerging spatial transcriptomic technologies provide a tremendous opportunity to systematically detect ligand-receptor signaling, but no method operates at cellular resolution in the spatial context. We developed CytoSignal to infer the locations and dynamics of cell-cell communication at cellular resolution from spatial transcriptomic data. CytoSignal is based on the simple insight that signaling is a protein-protein interaction that occurs at a specific tissue location when ligand and receptor are expressed in close spatial proximity. Our cellular-resolution, spatially-resolved signaling scores allow several novel types of analyses: we identify spatial gradients in signaling strength; separately quantify the locations of contact-dependent and diffusible interactions; and detect signaling-associated differentially expressed genes. Additionally, we can predict the temporal dynamics of a signaling interaction at each spatial location. CytoSignal is compatible with nearly every kind of spatial transcriptomic technology including FISH-based protocols and spot-based protocols without deconvolution. We experimentally validate our results in situ by proximity ligation assay, confirming that CytoSignal scores closely match the tissue locations of ligand-receptor protein-protein interactions. Our work addresses the field’s current need for a robust and scalable tool to detect cell-cell signaling interactions and their dynamics at cellular resolution from spatial transcriptomic data.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA",
    "University of Texas Health Science Center at Houston School of Dentistry, Houston, TX, USA",
    "Department of Electrical Engineering and Computer Science, University of Michigan, Ann Arbor, MI, USA",
    "Department of Electrical and Computer Engineering, University of Michigan, Ann Arbor, MI, USA",
    "Department of Medicine, Emory University, Atlanta, GA, USA",
    "Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA. welchjd@umich.edu",
    "Department of Computer Science and Engineering, University of Michigan, Ann Arbor, MI, USA. welchjd@umich.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jialin Liu",
      "orcid": "0000-0002-9984-7695"
    },
    {
      "affs": [
        1
      ],
      "name": "Hiroaki Manabe"
    },
    {
      "affs": [
        0
      ],
      "name": "Weizhou Qian",
      "orcid": "0000-0003-3884-7920"
    },
    {
      "affs": [
        1,
        0
      ],
      "name": "Shion Orikasa",
      "orcid": "0000-0002-4226-7358"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Javid Ghaemmaghami"
    },
    {
      "affs": [
        0
      ],
      "name": "Yichen Wang",
      "orcid": "0000-0003-4347-5199"
    },
    {
      "affs": [
        3,
        0
      ],
      "name": "Yichen Gu",
      "orcid": "0000-0001-6585-9236"
    },
    {
      "affs": [
        0
      ],
      "name": "Angel Ka Yan Chu"
    },
    {
      "affs": [
        0,
        1
      ],
      "name": "Gaurav T. Gadhvi",
      "orcid": "0000-0002-4379-2824"
    },
    {
      "affs": [
        0,
        2
      ],
      "name": "Yuxuan Song",
      "orcid": "0000-0002-5883-1208"
    },
    {
      "affs": [
        4
      ],
      "name": "Patrick McClinden"
    },
    {
      "affs": [
        4
      ],
      "name": "Vibha N. Lama"
    },
    {
      "affs": [
        1
      ],
      "name": "Noriaki Ono",
      "orcid": "0000-0002-3771-8230"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Joshua D. Welch",
      "orcid": "0000-0002-5869-2391"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8znwgpz4gj9nx.bib",
  "cited_by": 20,
  "doi": "10.1038/s41588-026-02624-9",
  "fulltext_url": null,
  "id": "8znwgpz4gj9nx",
  "issns": [
    "1061-4036",
    "1546-1718"
  ],
  "landing_url": "https://doi.org/10.1038/s41588-026-02624-9",
  "language": "en",
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W4392748138",
  "pdf_url": null,
  "pmcid": "PMC13263138",
  "pmid": "42271087",
  "published": "2026-06-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/8znwgpz4gj9nx.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
      "native_id": "W4392748138",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41588-026-02624-9"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "CytoSignal detects locations and dynamics of ligand–receptor signaling at cellular resolution from spatial transcriptomic data",
  "title_text": "CytoSignal detects locations and dynamics of ligand–receptor signaling at cellular resolution from spatial transcriptomic data",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/8znwgpz4gj9nx",
  "venue": "Nature Genetics",
  "versions": []
}