{
  "abstract": "Advances in single-cell and -nucleus transcriptomics have enabled generation of increasingly large-scale datasets from hundreds of subjects and millions of cells. These studies promise to give unprecedented insight into the cell type specific biology of human disease. Yet performing differential expression analyses across subjects remains difficult due to challenges in statistical modeling of these complex studies and scaling analyses to large datasets. Our open-source R package dreamlet (DiseaseNeurogenomics.github.io/dreamlet) uses a pseudobulk approach based on precision-weighted linear mixed models to identify genes differentially expressed with traits across subjects for each cell cluster. Designed for data from large cohorts, dreamlet is substantially faster and uses less memory than existing workflows, while supporting complex statistical models and controlling the false positive rate. We demonstrate computational and statistical performance on published datasets, and a novel dataset of 1.4M single nuclei from postmortem brains of 150 Alzheimer's disease cases and 149 controls.",
  "abstract_shown": true,
  "affiliations": [
    "Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. gabriel.hoffman@mssm.edu",
    "Center for Precision Medicine and Translational Therapeutics, Mental Illness Research, Education and Clinical Centers, James J. Peters VA Medical Center, Bronx, New York, NY, USA. gabriel.hoffman@mssm.edu",
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. gabriel.hoffman@mssm.edu",
    "Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. gabriel.hoffman@mssm.edu",
    "Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. gabriel.hoffman@mssm.edu",
    "Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Center for Precision Medicine and Translational Therapeutics, Mental Illness Research, Education and Clinical Centers, James J. Peters VA Medical Center, Bronx, New York, NY, USA",
    "Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA",
    "Center for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu",
    "Center for Precision Medicine and Translational Therapeutics, Mental Illness Research, Education and Clinical Centers, James J. Peters VA Medical Center, Bronx, New York, NY, USA. panagiotis.roussos@mssm.edu",
    "Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu",
    "Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu",
    "Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu",
    "Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. panagiotis.roussos@mssm.edu"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 15,
  "authors": [
    {
      "affs": [
        0,
        1,
        2,
        3,
        4
      ],
      "name": "Gabriel E. Hoffman",
      "orcid": "0000-0002-0957-0224"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Donghoon Lee",
      "orcid": "0000-0003-0453-6059"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Jaroslav M. Bendl",
      "orcid": "0000-0001-9989-2720"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "N. M. Prashant",
      "orcid": "0000-0003-3548-5637"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Aram Hong",
      "orcid": "0009-0000-6083-1998"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Clara Casey",
      "orcid": "0009-0002-9430-3557"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Marcela Alvia",
      "orcid": "0000-0001-9706-1376"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Zhiping Shao",
      "orcid": "0009-0006-4889-6637"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Stathis Argyriou",
      "orcid": "0009-0008-0713-6599"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Karen Therrien",
      "orcid": "0000-0003-3351-7260"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "Sanan Venkatesh",
      "orcid": "0000-0002-3094-2731"
    },
    {
      "affs": [
        5,
        9,
        6,
        7,
        8
      ],
      "name": "Georgios Voloudakis",
      "orcid": "0000-0002-5729-632X"
    },
    {
      "affs": [
        9,
        10,
        7
      ],
      "name": "Vahram H. Haroutunian",
      "orcid": "0000-0001-5860-2512"
    },
    {
      "affs": [
        5,
        6,
        7,
        8
      ],
      "name": "John F. Fullard",
      "orcid": "0000-0001-9874-2907"
    },
    {
      "affs": [
        11,
        12,
        13,
        14,
        15,
        16
      ],
      "name": "Panos Roussos",
      "orcid": "0000-0002-4640-6239"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bt0er68d5n4zy.bib",
  "cited_by": 75,
  "doi": "10.1038/s41467-026-75680-8",
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  "id": "bt0er68d5n4zy",
  "issns": [
    "2041-1723"
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  "landing_url": "https://doi.org/10.1038/s41467-026-75680-8",
  "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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      "openalex",
      "1312|Single-cell and spatial transcriptomics"
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  "pdf_url": "https://www.nature.com/articles/s41467-026-75680-8.pdf",
  "pmcid": "PMC10055252",
  "pmid": "36993704",
  "published": "2026-09-23",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/bt0er68d5n4zy.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:26:46Z",
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      "url": "https://doi.org/10.1038/s41467-026-75680-8"
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  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Efficient differential expression analysis of large-scale single-cell transcriptomics data using Dreamlet",
  "title_text": "Efficient differential expression analysis of large-scale single-cell transcriptomics data using Dreamlet",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:41Z",
  "url": "https://research.draconitic.com/paper/bt0er68d5n4zy",
  "venue": "Nature Communications",
  "versions": []
}