{
  "abstract": "Gene regulatory networks modulate the expression of the genome in response to signals and environmental conditions. Reconstructions of such networks can reveal the control principles cells use to maintain homeostasis and execute cell-state transitions. Here, we introduce a computational framework, dimension-scalable single-cell perturbation integration network (D-SPIN), that infers mechanistically interpretable and generative models of gene regulatory networks from single-cell mRNA-seq datasets collected across thousands of perturbation conditions. The models explain how perturbations modulate cell-state proportions by reconfiguring underlying regulatory interactions. Using large Perturb-seq and drug response datasets, D-SPIN models reveal key regulators of cell fate decisions and the coordination of distant cellular pathways in response to gene knockdowns and drug treatments, elucidate how combinations of immunomodulatory drugs induce combinatorial cell states through additive recruitment of gene expression programs, and simulate shifts in immune cell population structures across unobserved drug dosage combinations. D-SPIN provides a computational framework for revealing principles of cellular information processing and physiological control.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Center for Studies in Physics and Biology, The Rockefeller University, New York, NY, USA. Electronic address: jiangjl@rockefeller.edu",
    "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Beckman Single-Cell Profiling and Engineering Center, California Institute of Technology, Pasadena, CA, USA",
    "Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Department of Pathology, School of Medicine, Stanford University, Palo Alto, CA, USA; Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA",
    "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA",
    "Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA",
    "Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA",
    "Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA, USA; Center for Advanced Technology, University of California, San Francisco, San Francisco, CA, USA",
    "Department of Physics, Simon Fraser University, Burnaby, BC, Canada",
    "Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA; Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA; Chan Zuckerberg Biohub, San Francisco, San Francisco, CA, USA; Center for Cellular Construction, University of California, San Francisco, San Francisco, CA, USA",
    "Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Beckman Single-Cell Profiling and Engineering Center, California Institute of Technology, Pasadena, CA, USA. Electronic address: mthomson@caltech.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Jialong Jiang"
    },
    {
      "affs": [
        1
      ],
      "name": "Sisi Chen"
    },
    {
      "affs": [
        1
      ],
      "name": "Tiffany Tsou",
      "orcid": "0000-0002-5651-2879"
    },
    {
      "affs": [
        2
      ],
      "name": "Christopher S. McGinnis",
      "orcid": "0000-0001-6923-9341"
    },
    {
      "affs": [
        3
      ],
      "name": "Tahmineh Khazaei",
      "orcid": "0000-0002-4743-2383"
    },
    {
      "affs": [
        4
      ],
      "name": "Qin Zhu",
      "orcid": "0000-0001-5539-6071"
    },
    {
      "affs": [
        1
      ],
      "name": "Jong Hyeok Park",
      "orcid": "0000-0002-6629-3147"
    },
    {
      "affs": [
        3
      ],
      "name": "Inna-Marie Strazhnik"
    },
    {
      "affs": [
        3
      ],
      "name": "Jost Vielmetter",
      "orcid": "0000-0002-4314-7163"
    },
    {
      "affs": [
        3
      ],
      "name": "Yingying Gong"
    },
    {
      "affs": [
        5
      ],
      "name": "John Hanna"
    },
    {
      "affs": [
        6
      ],
      "name": "Eric D. Chow",
      "orcid": "0000-0001-8079-918X"
    },
    {
      "affs": [
        7
      ],
      "name": "David A. Sivak",
      "orcid": "0000-0003-4815-4722"
    },
    {
      "affs": [
        8
      ],
      "name": "Zev J. Gartner",
      "orcid": "0000-0001-7803-1219"
    },
    {
      "affs": [
        9
      ],
      "name": "Matt W. Thomson",
      "orcid": "0000-0003-1021-1234"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/0g6sjq5geexrp.bib",
  "cited_by": 31,
  "doi": "10.1016/j.cell.2026.04.028",
  "fulltext_url": null,
  "id": "0g6sjq5geexrp",
  "issns": [
    "0092-8674",
    "1097-4172"
  ],
  "landing_url": "https://doi.org/10.1016/j.cell.2026.04.028",
  "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|Gene Regulatory Network Analysis"
    ]
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  "openalex": "W7160895022",
  "pdf_url": null,
  "pmcid": "PMC13387596",
  "pmid": "42127893",
  "published": "2026-05-12",
  "publisher": "Cell Press",
  "ris": "https://research.draconitic.com/paper/0g6sjq5geexrp.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:48Z",
      "native_id": "W7160895022",
      "source": "openalex",
      "url": "https://doi.org/10.1016/j.cell.2026.04.028"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Gene Regulatory Network Analysis",
      "subfield": "molecular-biology"
    }
  ],
  "title": "D-SPIN constructs regulatory network models from scRNA-seq that reveal organizing principles of perturbation response",
  "title_text": "D-SPIN constructs regulatory network models from scRNA-seq that reveal organizing principles of perturbation response",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/0g6sjq5geexrp",
  "venue": "Cell",
  "versions": []
}