{
  "abstract": "Mapping enhancers and their target genes in specific cell types is crucial for understanding gene regulation and human disease genetics. However, accurately predicting enhancer-gene regulatory interactions from single-cell datasets has been challenging. Here we introduce a family of classification models, scE2G, to predict enhancer-gene regulation. These models use features from single-cell assay for transposase-accessible chromatin with sequencing (ATAC-seq) or multiomic RNA and ATAC-seq data, and are trained on a CRISPR perturbation dataset including >10,000 evaluated element-gene pairs. We benchmark scE2G models against CRISPR perturbations, fine-mapped expression quantitative trait loci and genome-wide association study variant-gene associations and demonstrate state-of-the-art performance at prediction tasks across several cell types and categories of perturbations. We apply scE2G to build maps of enhancer-gene regulatory interactions in heterogeneous tissues and interpret noncoding variants associated with complex traits, nominating regulatory interactions linking INPP4B and IL15 to lymphocyte count. The scE2G models will enable accurate mapping of enhancer-gene regulatory interactions across thousands of human cell types.",
  "abstract_shown": true,
  "affiliations": [
    "Basic Sciences and Engineering Initiative, Betty Irene Moore Children's Heart Center, Lucile Packard Children's Hospital, Stanford, CA, USA",
    "Department of Bioengineering, Stanford University, Stanford, CA, USA",
    "Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA",
    "The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA",
    "Stanford University",
    "Department of Biology, Section for Computational and RNA Biology, University of Copenhagen, Copenhagen, Denmark",
    "University of Copenhagen",
    "Broad Institute",
    "Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA, USA",
    "Stanford University School of Medicine",
    "Department of Pathology, Stanford University, Stanford, CA, USA",
    "Parker Institute for Cancer Immunotherapy, San Francisco, CA, USA",
    "University of San Diego",
    "Genome Biology Unit, European Molecular Biology Laboratory (EMBL), Heidelberg, Germany",
    "Stanford Genome Technology Center, Stanford University School of Medicine, Palo Alto, CA, USA",
    "Department of Computer Science, Stanford University, Stanford, CA, USA",
    "Halıcıoğlu Data Science Institute and Department of Computer Science and Engineering, University of California San Diego, San Diego, CA, USA",
    "Basic Sciences and Engineering Initiative, Betty Irene Moore Children's Heart Center, Lucile Packard Children's Hospital, Stanford, CA, USA. engreitz@stanford.edu",
    "Department of Genetics, Stanford University School of Medicine, Stanford, CA, USA. engreitz@stanford.edu",
    "Gene Regulation Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA. engreitz@stanford.edu",
    "Stanford Cardiovascular Institute, Stanford University School of Medicine, Stanford, CA, USA. engreitz@stanford.edu",
    "The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA. engreitz@stanford.edu",
    "Department of Biology, Section for Computational and RNA Biology, University of Copenhagen, Copenhagen, Denmark. robin@bio.ku.dk",
    "The Novo Nordisk Foundation Center for Genomic Mechanisms of Disease, Broad Institute of MIT and Harvard, Cambridge, MA, USA. robin@bio.ku.dk"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 23,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Maya U. Sheth",
      "orcid": "0000-0003-1466-8899"
    },
    {
      "affs": [
        5,
        3,
        6
      ],
      "name": "Wei‐Lin Qiu",
      "orcid": "0000-0002-6649-0378"
    },
    {
      "affs": [
        0,
        2,
        4
      ],
      "name": "X. Rosa Ma",
      "orcid": "0000-0001-8297-4279"
    },
    {
      "affs": [
        0,
        2,
        3,
        4
      ],
      "name": "Andreas R. Gschwind",
      "orcid": "0000-0002-0769-6907"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Evelyn Jagoda"
    },
    {
      "affs": [
        0,
        2,
        4
      ],
      "name": "Anthony S. Tan"
    },
    {
      "affs": [
        0,
        2,
        6
      ],
      "name": "James Galante",
      "orcid": "0000-0002-9289-3090"
    },
    {
      "affs": [
        3,
        7
      ],
      "name": "Judhajeet Ray",
      "orcid": "0000-0003-1524-2603"
    },
    {
      "affs": [
        0,
        2,
        3,
        4
      ],
      "name": "Dulguun Amgalan",
      "orcid": "0000-0001-6398-3372"
    },
    {
      "affs": [
        5,
        3,
        4
      ],
      "name": "Hjörleifur Einarsson",
      "orcid": "0000-0002-0565-9053"
    },
    {
      "affs": [
        8,
        3,
        4
      ],
      "name": "Bram L. Gorissen",
      "orcid": "0000-0001-5992-0432"
    },
    {
      "affs": [
        2,
        9
      ],
      "name": "Danilo Dubocanin",
      "orcid": "0000-0003-0330-5814"
    },
    {
      "affs": [
        10,
        11,
        7
      ],
      "name": "Christopher S. McGinnis",
      "orcid": "0000-0001-6923-9341"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Jacob Huang",
      "orcid": "0009-0005-8757-6540"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Glen Munson"
    },
    {
      "affs": [
        0,
        2,
        12
      ],
      "name": "Kayla Brand",
      "orcid": "0000-0002-8879-628X"
    },
    {
      "affs": [
        10,
        11,
        4
      ],
      "name": "Ansuman T. Satpathy",
      "orcid": "0000-0002-5167-537X"
    },
    {
      "affs": [
        3,
        6
      ],
      "name": "Thouis R. Jones",
      "orcid": "0000-0001-6584-9660"
    },
    {
      "affs": [
        2,
        13,
        14
      ],
      "name": "Lars Michael Steinmetz",
      "orcid": "0000-0002-3962-2865"
    },
    {
      "affs": [
        15,
        2
      ],
      "name": "Anshul Bharat Kundaje",
      "orcid": "0000-0003-3084-2287"
    },
    {
      "affs": [
        16
      ],
      "name": "Berk Ustun",
      "orcid": "0000-0001-5188-3155"
    },
    {
      "affs": [
        17,
        18,
        19,
        20,
        21
      ],
      "name": "J Engreitz",
      "orcid": "0000-0002-5754-1719"
    },
    {
      "affs": [
        22,
        23
      ],
      "name": "Robin Andersson",
      "orcid": "0000-0003-1516-879X"
    }
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  "bibtex": "https://research.draconitic.com/paper/fnda3wa1t8kd8.bib",
  "cited_by": 36,
  "doi": "10.1038/s41588-026-02695-8",
  "fulltext_url": null,
  "id": "fnda3wa1t8kd8",
  "issns": [
    "1061-4036",
    "1546-1718"
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  "landing_url": "https://doi.org/10.1038/s41588-026-02695-8",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
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  "pdf_url": "https://www.nature.com/articles/s41588-026-02695-8.pdf",
  "pmcid": "PMC11601566",
  "pmid": "39605382",
  "published": "2026-08-01",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/fnda3wa1t8kd8.ris",
  "sources": [
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      "url": "https://doi.org/10.1038/s41588-026-02695-8"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Genomics and Chromatin Dynamics",
      "subfield": "molecular-biology"
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  ],
  "title": "Mapping enhancer–gene regulatory interactions from single-cell data",
  "title_text": "Mapping enhancer–gene regulatory interactions from single-cell data",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T13:21:05Z",
  "url": "https://research.draconitic.com/paper/fnda3wa1t8kd8",
  "venue": "Nature Genetics",
  "versions": []
}