Evidence map›Paper›PMID 40954300›Full record

ArticleNature methods2025

Scaling up spatial transcriptomics for large-sized tissues: uncovering cellular-level tissue architecture beyond conventional platforms with iSCALE.

Amelia Schroeder, Melanie L Loth, Chunyu Luo, Sicong Yao, Hanying Yan, Daiwei Zhang, Sarbottam Piya, Edward Plowey, Wenxing Hu, Jean R Clemenceau and 13 more

Abstract read
In one paragraph

Article in Nature methods, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed.

  1. Mesolens imaging in microbiology.Essays in biochemistry · 2026
    Review
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  14. Multimodal AI in precision medicine: linking omics, imaging and clinical decisions.American journal of clinical and experimental immunology · 2026
    Article
  15. Review
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  18. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

23 authors.

Amelia SchroederStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Melanie L LothStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Chunyu LuoStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0004-7047-0857
Sicong YaoStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Hanying YanStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9227-1742
Daiwei ZhangStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Sarbottam PiyaResearch Department, Biogen, Inc., Cambridge, MA, USA.
Edward PloweyResearch Department, Biogen, Inc., Cambridge, MA, USA.
Wenxing HuResearch Department, Biogen, Inc., Cambridge, MA, USA.
Jean R ClemenceauDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-6222-6457
Inyeop JangDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.
Minji KimDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0009-0009-6787-0354
Isabel BarnfatherDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0009-0007-3071-963X
Su Jing ChanResearch Department, Biogen, Inc., Cambridge, MA, USA.
Taylor L ReynoldsResearch Department, Biogen, Inc., Cambridge, MA, USA.
Thomas CarlileResearch Department, Biogen, Inc., Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-7699-9354
Patrick CullenResearch Department, Biogen, Inc., Cambridge, MA, USA.
Ji-Youn SungDepartment of Pathology, College of Medicine, Kyung Hee University Hospital, Kyung Hee University, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0002-6607-2117
Hui-Hsin TsaiResearch Department, Biogen, Inc., Cambridge, MA, USA.
Jeong Hwan ParkDepartment of Pathology, Seoul Metropolitan Government-Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Seoul, Republic of Korea.ORCID http://orcid.org/0000-0003-4522-9928
Tae Hyun HwangDepartment of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA. taehyun.hwang@vumc.org.ORCID http://orcid.org/0000-0002-6668-7269
Baohong ZhangResearch Department, Biogen, Inc., Cambridge, MA, USA. baohongz@gmail.com.ORCID http://orcid.org/0000-0003-4735-4212
Mingyao LiStatistical Center for Single-Cell and Spatial Genomics, Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. mingyao@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0001-8180-0621

Funding

Clinical and Translational Science AwardUL1TR001873 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI REILLY, MUREDACH P · 2016 to 2025
$99.0M
Center for Gastric Pre-Cancer Atlas of Multidimensional Evolution in 3D (GAME3D)U01CA294518 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Paul F Mansfield, Linghua Wang · 2024 to 2026
$5.4M
Determining the role of germline CDH1 variants in gastric cancer outcome disparities in Hispanic/Latino patientsR37CA265967 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Sam C. Wang · 2022 to 2026
$3.6M
Integrative analysis of spatial transcriptomics with histology images and single cellsR01HG013185 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Mingyao Li · 2023 to 2026
$2.2M
Integration of spatial transcriptomics, genetics, and histomorphology for causal inference in atherosclerotic cardiovascular diseaseR01HL171595 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Muredach P Reilly · 2024 to 2026
$2.0M
Using artificial intelligence to discover spatial, genomic, and pathologic biomarkers to guide and augment immune checkpoint inhibitor therapy for gastric cancerR01CA276690 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI Tae Hyun Hwang, Sam C. Wang · 2024 to 2026
$2.0M
Sox9 signaling in lung adenocarcinomaR01CA190578 · NCI · RBHS -CANCER INSTITUTE OF NEW JERSEY · PI PINE, SHARON R. · 2014 to 2018
$1.7M
Developing informatics tools to predict virtual spatial transcriptomics data with single-cell resolution in large-scale studiesR01LM014592 · NLM · UNIVERSITY OF PENNSYLVANIA · PI Mingyao Li · 2024 to 2026
$1.1M
NCATS NIH HHS UL1 TR001873NCI NIH HHS R01 CA190578NCI NIH HHS R01 CA276690NCI NIH HHS R37 CA265967NCI NIH HHS U01 CA294518NHGRI NIH HHS R01 HG013185NHLBI NIH HHS R01 HL171595NLM NIH HHS R01 LM014592U.S. Department of Defense (United States Department of Defense) CA190578U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA276690U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R37CA265967U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U01CA294518U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI) R01HL171595U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG013185U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine (NLM) R01LM014592
6 · The paper itself

Abstract

Recent advances in spatial transcriptomics (ST) technologies have transformed our ability to profile gene expression while preserving crucial spatial context within tissues. However, existing ST platforms are constrained by high costs, long turnaround times, low resolution, limited gene coverage and inherently small tissue capture areas, which hinder their broad applications. Here we present iSCALE, a method that reconstructs large-scale, super-resolution gene expression landscapes and automatically annotates cellular-level tissue architecture in samples exceeding capture areas of current ST platforms. The performance of iSCALE was assessed by comprehensive evaluations involving benchmarking experiments, immunohistochemistry staining and manual annotations by pathologists. When applied to multiple sclerosis human brain samples, iSCALE uncovered lesion-associated cellular characteristics undetectable by conventional ST experiments. Our results demonstrate the utility of iSCALE in analyzing large tissues by enabling unbiased annotation, resolving cell type composition, mapping cellular microenvironments and revealing spatial features beyond the reach of standard ST analysis or routine histopathological assessment.

Indexed as

Gene Expression ProfilingTranscriptomeBrainHumansMultiple Sclerosis

Identifiers

PMID40954300
PMCPMC12443328

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.