Evidence map›Paper›PMID 41540123›Full record

ArticleNature methods2026

Integration of imaging-based and sequencing-based spatial omics mapping on the same tissue section via DBiTplus.

Archibald Enninful, Zhaojun Zhang, Dmytro Klymyshyn, Matthew Ingalls, Mingyu Yang, Hailing Zong, Zhiliang Bai, Negin Farzad, Graham Su, Alev Baysoy and 9 more

Abstract read
In one paragraph

Article in Nature methods, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing 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

21 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Review
  12. A Guide for Spatial Omics Technologies: Innovation, Evaluation, and Application.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  13. Review
  14. Article
  15. Review
  16. Toward Computationally Complete Spatial Omics.bioRxiv : the preprint server for biology · 2026
    Article
  17. An update on spatial proteomics.Nature methods · 2026
    Article
  18. Review
  19. Review
  20. Visualizing Epigenetics: A Review of Microscopy Techniques for Investigating DNA Methylation Patterns, Chromatin Structure, and Gene Expression.Microscopy and microanalysis : the official journal of Microscopy Society of America, Microbeam Analysis Society, Microscopical Society of Canada · 2025
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

19 authors.

Archibald Enninful *Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Zhaojun Zhang *Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.
Dmytro KlymyshynAkoya Biosciences, Menlo Park, CA, USA.
Matthew IngallsBruker Spatial Biology, St Louis, MO, USA.ORCID http://orcid.org/0000-0001-6430-9785
Mingyu YangDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-0986-3825
Hailing ZongAkoya Biosciences, Menlo Park, CA, USA.
Zhiliang BaiDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-3977-3057
Negin FarzadDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Graham SuDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Alev BaysoyDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Jungmin NamDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-6717-1328
Yao LuDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Shuozhen BaoDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Siyan DengDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Nancy R ZhangDepartment of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0880-5749
Oliver BraubachBruker Spatial Biology, St Louis, MO, USA.
Mina L XuDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA. mina.xu@yale.edu.ORCID http://orcid.org/0000-0001-9513-245X
Zongming MaDepartment of Statistics and Data Science, Yale University, New Haven, CT, USA. zongming.ma@yale.edu.ORCID http://orcid.org/0000-0003-2401-0177
Rong FanDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA. rong.fan@yale.edu.ORCID http://orcid.org/0000-0001-7805-8059

Funding

Systems investigation of vaccine responses in B cell depleted autoimmune patientsU19AI089992 · NIAID · YALE UNIVERSITY · PI Steven H. Kleinstein · 2010 to 2026
$50.4M
Spatiotemporal Tumor Analytics for Guiding Sequential Targeted-Inhibitor: Immunotherapy Combinations (ST-Analytics)U54CA274509 · NCI · INSTITUTE FOR SYSTEMS BIOLOGY · PI Rong Fan · 2022 to 2026
$15.6M
Tech Core 2U54CA268083 · NCI · JOHNS HOPKINS UNIVERSITY · PI Denis Wirtz, Laura DeLong Wood · 2022 to 2026
$10.2M
Yale TMC for Cellular Senescence in Lymphoid OrgansU54AG076043 · NIA · YALE UNIVERSITY · PI KLUGER, YUVAL · 2021 to 2025
$7.0M
Yale Murine-TMC on Immune Cell Senescence Derived InflammationU54AG079759 · NIA · YALE UNIVERSITY · PI KLUGER, YUVAL · 2022 to 2025
$6.5M
High-throughput in vivo and in vitro functional and multi-omics screens of neuropsychiatric and neurodevelopmental disorder risk genesRM1MH132648 · NIMH · YALE UNIVERSITY · PI Kristen Jennifer Brennand, Rong Fan · 2023 to 2026
$5.6M
Center for Human Lymphoma Spatiotemporal Atlas (HuLymSTA)U01CA294514 · NCI · YALE UNIVERSITY · PI FAN, RONG, HALENE, STEPHANIE · 2024 to 2025
$5.1M
Highly scalable and sensitive spatial transcriptomic and epigenomic sequencing of brain tissues from human and non-human primateRF1MH128876 · NIMH · YALE UNIVERSITY · PI FAN, RONG, SESTAN, NENAD · 2021 to 2021
$2.9M
Ex vivo analysis of human brain tumor cells in a microvascular niche modelR01CA245313 · NCI · YALE UNIVERSITY · PI FAN, RONG, ZHOU, JIANGBING · 2020 to 2024
$2.6M
High-spatial-resolution ECM-inclusive multi-omics sequencing of human PFA and FFPE tissue slidesUH3CA257393 · NCI · YALE UNIVERSITY · PI FAN, RONG · 2022 to 2023
$1.2M
High-spatial-resolution ECM-inclusive multi-omics sequencing of human PFA and FFPE tissue slidesUG3CA257393 · NCI · YALE UNIVERSITY · PI FAN, RONG · 2020 to 2021
$800k
Center for Selective C-H Functionalization, National Science Foundation 2245575National Science Foundation (NSF) 2245575National Science Foundation (NSF) 2345215NCI NIH HHS R01 CA245313NCI NIH HHS U01 CA294514NCI NIH HHS U54 CA268083NCI NIH HHS U54 CA274509NCI NIH HHS UG3 CA257393NCI NIH HHS UH3 CA257393NIAID NIH HHS U19 AI089992NIA NIH HHS U54 AG076043NIA NIH HHS U54 AG079759NIMH NIH HHS RF1 MH128876NIMH NIH HHS RM1 MH132648U.S. Department of Health & Human Services | National Institutes of Health (NIH) RF1MH128876U.S. Department of Health & Human Services | National Institutes of Health (NIH) RM1MH132648U.S. Department of Health & Human Services | National Institutes of Health (NIH) U01CA294514U.S. Department of Health & Human Services | National Institutes of Health (NIH) U54AG076043U.S. Department of Health & Human Services | National Institutes of Health (NIH) U54AG079759U.S. Department of Health & Human Services | National Institutes of Health (NIH) UH3CA257393U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) R01CA245313U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54CA268083U.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI) U54CA274509
6 · The paper itself

Abstract

Spatially mapping the transcriptome and proteome in the same tissue section can profoundly advance our understanding of cellular heterogeneity and function. Here we present Deterministic Barcoding in Tissue sequencing plus (DBiTplus), an integrative multimodal spatial omics approach combining sequencing-based spatial transcriptomics and multiplexed protein imaging on the same section, enabling both single-cell-resolution cell typing and transcriptome-wide interrogation of biological pathways. DBiTplus utilizes spatial barcoding and RNase H-mediated cDNA retrieval, preserving tissue architecture for multiplexed protein imaging. We developed computational pipelines to integrate these modalities, allowing imaging-guided deconvolution to generate single-cell-resolved spatial transcriptome atlases. We demonstrate DBiTplus across diverse samples including frozen mouse embryos, and formalin-fixed paraffin-embedded human lymph nodes and lymphoma tissues, highlighting its compatibility with challenging clinical specimens. DBiTplus uncovered mechanisms of lymphomagenesis, progression and transformation in human lymphomas. Thus, DBiTplus is a unified workflow for spatially resolved single-cell atlasing and unbiased exploration of biological mechanisms in a cell-by-cell manner at transcriptome scale.

Indexed as

Gene Expression ProfilingAnimalsHumansLymphomaMiceMultiomicsProteomeSingle-Cell AnalysisSingle-Cell Gene Expression AnalysisSpatial TranscriptomicsTranscriptomeProteome

Identifiers

PMID41540123
PMCPMC13541625

What Socratic holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 Socratic graph.