{
  "abstract": "Spatial omics technologies have revolutionized the study of tissue architecture and cellular heterogeneity by integrating molecular profiles with spatial localization. In spatially resolved transcriptomics, delineating higher-order anatomical structures is critical for understanding how cellular organization affects tissue and organ function. Since 2020, more than 50 spatially aware clustering (SAC) methods have been developed for this purpose. However, the reliability of current benchmarks is undermined by their narrow focus on Visium and brain tissue datasets, as well as incorrect interpretation of manual annotation as ground truth. Here, we present SACCELERATOR, a community-driven, extensible framework that standardizes data formatting, method integration, and metric evaluation, and is designed to rapidly incorporate new methods and datasets. SACCELERATOR currently includes 22 SAC methods applied to 15 datasets spanning 9 technologies and diverse tissue types. Our analysis revealed substantial limitations in the generalizability and reproducibility of SAC methods across tissues and platforms. We also demonstrate that anatomical labels commonly used as ground truths are often biased, potentially error-prone, and, in some cases, unsuitable for benchmarking efforts. Rather than scoring and comparing methods, we propose a consensus-guided workflow that aggregates clustering results to generate consensus representations. Descriptive spatial metrics highlight areas of high entropy where method disagreement is highest, enabling targeted feedback for tissue experts. Applied to brain and cancer datasets, this approach uncovered biologically meaningful patterns overlooked by individual methods and manual annotations. Our results underscore the need for iterative, expert-in-the-loop analysis and reveal that traditional evaluation metrics do not always capture the subjective qualities of results. By improving tissue annotation and addressing key benchmarking limitations, SACCELERATOR provides a robust foundation for advancing spatial omics research.",
  "abstract_shown": true,
  "affiliations": [
    "Biomedical Data Science Center, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland",
    "Biomedical Data Science Center, Centre Hospitalier Universitaire Vaudois, Rue du Bugnon 2, 0 Lausanne, Switzerland",
    "Delft Bioinformatics Lab, Delft University of Technology, Delft, the Netherlands",
    "Department of Human Genetics, Leiden University Medical Center, Leiden, the Netherlands",
    "Delft Bioinformatics Lab, Delft University of Technology, Van Mourik Broekmanweg 6, 2628 XE Delft, Netherlands",
    "Department of Human Genetics, Leiden University Medical Center, Einthovenweg 0, 333 ZC Leiden, Netherlands",
    "Department of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, Zurich, Switzerland",
    "Department of Molecular Life Sciences and SIB Swiss Institute of Bioinformatics, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland",
    "Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Center of Digital, Berlin, Germany",
    "Berlin Institute of Health at Charité – Universitätsmedizin Berlin, Center of Digital Health, Charitéplatz 1, 10117 Berlin, Germany",
    "Department of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH Aachen, Aachen, Germany",
    "Department of Nephrology, Rheumatology, and Clinical Immunology, University Hospital RWTH Aachen, Pauwelsstraße 30, Aachen, Germany",
    "Allen Institute for Brain Science, Seattle, WA, USA",
    "Allen Institute for Brain Science, 615 Westlake Ave N, Seattle, WA, USA 98109",
    "DTU Health Tech, Technical University of Denmark, Ørsteds Plads, Kongens Lyngby, Denmark",
    "LEO Foundation Skin Immunology Research Center, Department of Immunology and Microbiology, University of Copenhagen, Copenhagen, Denmark",
    "German Cancer Research Center (DKFZ), Division of Computational Genomics and Systems Genetics, Heidelberg, Germany",
    "The German Human Genome-Phenome Archive, Heidelberg, Germany",
    "German Cancer Research Center (DKFZ), Division of Computational Genomics and Systems Genetics, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany",
    "Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, Medical University of Graz, Graz, Austria",
    "Diagnostic and Research Institute of Pathology, Medical University of Graz, Graz, Austria",
    "Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, MI, USA",
    "Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA, USA",
    "CIMA Universidad de Navarra, Pamplona, Spain",
    "Department of Biomedical Informatics, College of Medicine, Ohio State University, Columbus, OH, USA",
    "Allen Institute for Neural Dynamics, Seattle, WA, USA",
    "Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore",
    "Nature Genetics, Berlin, Germany",
    "Institute of Applied Biosciences, Centre for Research and Technology Hellas, Thessaloniki, Greece",
    "Biozentrum, University of Basel, Basel, Switzerland",
    "SIB Swiss Institute of Bioinformatics, Quartier Sorge Batiment Amphipole, Lausanne, Switzerland",
    "Helmholtz Zentrum München, Institute of Computational Biology, Neuherberg, Germany",
    "CSEM, Allschwil, Switzerland",
    "ETHZ, BMIC - Biomedical Image Computing lab, Zurich, Switzerland",
    "OMAPiX GmbH Raiffeisenstraße 3, Langenfeld, Germany",
    "Technical University of Munich, School of Medicine, Institute of Virology, Munich, Germany",
    "University of Michigan, Undergraduate Research Opportunity Program, Ann Arbor, MI, USA",
    "Department of Informatics and Chemistry, Faculty of Chemical Technology, University of Chemistry and Technology, Prague, Czech Republic",
    "Laboratory of Genomics and Bioinformatics, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic",
    "Department of Biology and Biological Engineering, Chalmers University of Technology, Gothenburg, Sweden"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 55,
  "authors": [
    {
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        0,
        1
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      "name": "Jieran Sun",
      "orcid": "0000-0002-7996-3840"
    },
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        2,
        3,
        4,
        5
      ],
      "name": "Kirti Biharie",
      "orcid": "0000-0002-8274-8439"
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        6,
        7
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      "name": "Peiying Cai",
      "orcid": "0009-0001-9229-2244"
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        9
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      "name": "Niklas Müller‐Bötticher",
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      "name": "Paul Kießling",
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      "name": "Meghan A. Turner",
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      "name": "Søren Helweg Dam",
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        18
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      "name": "Florian Heyl",
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      "name": "Sarusan Kathirchelvan"
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      "name": "Martin Emons",
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      "name": "Samuel Gunz",
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        9
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      "name": "Sven Olaf Twardziok",
      "orcid": "0000-0002-0326-5704"
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        19
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      "name": "Amin El Heliebi",
      "orcid": "0000-0002-7679-6856"
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      ],
      "name": "Martin Zacharias",
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        4
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      "name": "SpaceHack 2.0 participants"
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        9
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      "name": "Søren Helweg Dam",
      "orcid": "0000-0003-0755-0016"
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    {
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        1
      ],
      "name": "Fadhl Alakwaa",
      "orcid": "0000-0001-5349-7960"
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    {
      "affs": [
        22,
        11
      ],
      "name": "Shahul Alam",
      "orcid": "0000-0002-4821-7079"
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    {
      "affs": [
        23,
        13
      ],
      "name": "Maria Calleja"
    },
    {
      "affs": [
        24,
        4,
        5
      ],
      "name": "Yuzhou Chang"
    },
    {
      "affs": [
        25,
        7
      ],
      "name": "Thomas Chartrand",
      "orcid": "0000-0002-7093-8681"
    },
    {
      "affs": [
        26,
        9
      ],
      "name": "Nigel Chou",
      "orcid": "0000-0002-6280-7729"
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    {
      "affs": [
        0
      ],
      "name": "Estella Y. Dong"
    },
    {
      "affs": [
        27
      ],
      "name": "Michael Fletcher"
    },
    {
      "affs": [
        8,
        28
      ],
      "name": "George Gavriilidis"
    },
    {
      "affs": [
        29,
        30
      ],
      "name": "Alexander Kanitz",
      "orcid": "0000-0002-3468-0652"
    },
    {
      "affs": [
        16,
        17
      ],
      "name": "Sameesh Kher"
    },
    {
      "affs": [
        31
      ],
      "name": "Louis Benedikt Kuemmerle"
    },
    {
      "affs": [
        32,
        33
      ],
      "name": "Francesca A. Luongo"
    },
    {
      "affs": [
        2
      ],
      "name": "Qirong Mao",
      "orcid": "0000-0002-0616-4431"
    },
    {
      "affs": [
        14,
        15
      ],
      "name": "Giorgia Moranzoni",
      "orcid": "0000-0001-8065-6277"
    },
    {
      "affs": [
        34
      ],
      "name": "Mar M. Moreno"
    },
    {
      "affs": [
        35
      ],
      "name": "Anastasiia Okhtienko",
      "orcid": "0009-0003-5886-811X"
    },
    {
      "affs": [
        36
      ],
      "name": "Lena Perry"
    },
    {
      "affs": [
        37,
        38
      ],
      "name": "Lucie Pfeiferová",
      "orcid": "0000-0003-1089-0329"
    },
    {
      "affs": [
        10
      ],
      "name": "Daryna Pikulska",
      "orcid": "0009-0005-1638-0268"
    },
    {
      "affs": [
        26
      ],
      "name": "Shyam Prabhakar",
      "orcid": "0000-0002-6409-0661"
    },
    {
      "affs": [
        39
      ],
      "name": "Rasool Saghaleyni",
      "orcid": "0000-0003-0956-039X"
    },
    {
      "name": "Zaira Seferbekova",
      "orcid": "0000-0002-3131-3697"
    },
    {
      "affs": [
        26
      ],
      "name": "Vipul Singhal",
      "orcid": "0000-0003-1670-1824"
    },
    {
      "name": "Divya Sitani",
      "orcid": "0000-0001-5138-6108"
    },
    {
      "name": "Charlotte Soneson",
      "orcid": "0000-0003-3833-2169"
    },
    {
      "affs": [
        8
      ],
      "name": "Sebastian Tiesmeyer",
      "orcid": "0000-0002-0492-1523"
    },
    {
      "affs": [
        30
      ],
      "name": "Marco Varrone",
      "orcid": "0000-0002-0538-3464"
    },
    {
      "name": "Siao-Han Wong"
    },
    {
      "affs": [
        30
      ],
      "name": "Liya Zaygerman",
      "orcid": "0009-0005-4947-6223"
    },
    {
      "name": "Teresa Zulueta-Coarasa",
      "orcid": "0000-0002-0456-6912"
    },
    {
      "affs": [
        8
      ],
      "name": "Roland Eils",
      "orcid": "0000-0002-0034-4036"
    },
    {
      "affs": [
        2
      ],
      "name": "Marcel J. T. Reinders",
      "orcid": "0000-0002-1148-1562"
    },
    {
      "affs": [
        0
      ],
      "name": "Raphaël Gottardo",
      "orcid": "0000-0002-3867-0232"
    },
    {
      "affs": [
        10
      ],
      "name": "Christoph Kuppe",
      "orcid": "0000-0003-4597-9833"
    },
    {
      "name": "Brian Long",
      "orcid": "0000-0002-7793-5969"
    },
    {
      "name": "Ahmed Essam Mahfouz",
      "orcid": "0000-0001-8601-2149"
    },
    {
      "name": "Mark D. Robinson",
      "orcid": "0000-0002-3048-5518"
    },
    {
      "name": "Naveed Ishaque",
      "orcid": "0000-0002-8426-901X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/b6vnt33g9g2kz.bib",
  "cited_by": 9,
  "doi": "10.1038/s41592-026-03194-8",
  "fulltext_url": null,
  "id": "b6vnt33g9g2kz",
  "issns": [
    "1548-7091",
    "1548-7105"
  ],
  "landing_url": "https://doi.org/10.1038/s41592-026-03194-8",
  "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": [
    [
      "openalex",
      "1312|Single-cell and spatial transcriptomics"
    ]
  ],
  "openalex": "W4411721301",
  "pdf_url": "https://www.nature.com/articles/s41592-026-03194-8.pdf",
  "pmcid": "PMC12262716",
  "pmid": "40667282",
  "published": "2026-08-24",
  "publisher": "Nature Portfolio",
  "ris": "https://research.draconitic.com/paper/b6vnt33g9g2kz.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T13:20:30Z",
      "native_id": "W4411721301",
      "source": "openalex",
      "url": "https://doi.org/10.1038/s41592-026-03194-8"
    }
  ],
  "subjects": [
    {
      "field": "biochemistry",
      "origin": "openalex:1312|Single-cell and spatial transcriptomics",
      "subfield": "molecular-biology"
    }
  ],
  "title": "Beyond benchmarking: an expert-guided consensus approach to spatially aware clustering",
  "title_text": "Beyond benchmarking: an expert-guided consensus approach to spatially aware clustering",
  "type": "peer-reviewed",
  "updated_at": "2026-11-08T13:20:43Z",
  "url": "https://research.draconitic.com/paper/b6vnt33g9g2kz",
  "venue": "Nature Methods",
  "versions": []
}