Evidence map›Paper›PMID 40119005›Full record

ReviewNature protocols2025

Spatially resolved genome-wide joint profiling of epigenome and transcriptome with spatial-ATAC-RNA-seq and spatial-CUT&Tag-RNA-seq.

Haikuo Li, Shuozhen Bao, Negin Farzad, Xiaoyu Qin, Anthony A Fung, Di Zhang, Zhiliang Bai, Bo Tao, Rong Fan

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature protocols, 2025. 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. Insights Into Spatial Transcriptomics: Exploring Recent Technical Developments and Their Diverse Applications.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026
    Review
  3. Review
  4. Review
  5. Review
  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Review
  12. Review
  13. Review
  14. Review
  15. Review
  16. Computational Analyses and Challenges of Single-cell ATAC-seq.Genomics, proteomics & bioinformatics · 2025
    Review
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Haikuo LiDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0003-3697-5662
Shuozhen BaoDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0002-9301-9952
Negin FarzadDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0009-0002-5391-9363
Xiaoyu QinDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Anthony A FungDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0003-1631-7451
Di ZhangDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.
Zhiliang BaiDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA.ORCID 0000-0002-3977-3057
Bo TaoDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Rong FanDepartment of Biomedical Engineering, Yale University, New Haven, CT, USA. rong.fan@yale.edu.ORCID 0000-0001-7805-8059

Funding

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 Andrew Josef Ewald · 2022 to 2026
$10.2M
Yale TMC for Cellular Senescence in Lymphoid OrgansU54AG076043 · NIA · YALE UNIVERSITY · PI FAN, RONG, HALENE, STEPHANIE · 2021 to 2025
$7.0M
Yale Murine-TMC on Immune Cell Senescence Derived InflammationU54AG079759 · NIA · YALE UNIVERSITY · PI MONTGOMERY, RUTH R · 2022 to 2025
$6.5M
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
NCI NIH HHS U01 CA294514NCI NIH HHS U54 CA274509NCI NIH HHS UG3 CA257393NCI NIH HHS UH3 CA257393NIA NIH HHS U54 AG076043NIMH NIH HHS RF1 MH128876U.S. Department of Health & Human Services | National Institutes of Health (NIH) R01CA245313U.S. Department of Health & Human Services | National Institutes of Health (NIH) RF1MH128876U.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) U54CA268083U.S. Department of Health & Human Services | National Institutes of Health (NIH) U54CA274509U.S. Department of Health & Human Services | National Institutes of Health (NIH) UG3CA257393U.S. Department of Health & Human Services | National Institutes of Health (NIH) UH3CA257393
6 · The paper itself

Abstract

The epigenome of a cell is tightly correlated with gene transcription, which controls cell identity and diverse biological activities. Recent advances in spatial technologies have improved our understanding of tissue heterogeneity by analyzing transcriptomics or epigenomics with spatial information preserved, but have been mainly restricted to one molecular layer at a time. Here we present procedures for two spatially resolved sequencing methods, spatial-ATAC-RNA-seq and spatial-CUT&Tag-RNA-seq, that co-profile transcriptome and epigenome genome wide. In both methods, transcriptomic readouts are generated through tissue fixation, permeabilization and in situ reverse transcription. In spatial-ATAC-RNA-seq, Tn5 transposase is used to probe accessible chromatin, and in spatial-CUT&Tag-RNA-seq, the tissue is incubated with primary antibodies that target histone modifications, followed by Protein A-fused Tn5-induced tagmentation. Both methods leverage a microfluidic device that delivers two sets of oligonucleotide barcodes to generate a two-dimensional mosaic of tissue pixels at near single-cell resolution. A spatial-ATAC-RNA-seq or spatial-CUT&Tag-RNA-seq library can be generated in 3-5 d, allowing researchers to simultaneously investigate the transcriptomic landscape and epigenomic landscape of an intact tissue section. This protocol is an extension of our previous spatially resolved epigenome sequencing protocol and provides opportunities in multimodal profiling.

Indexed as

EpigenomeEpigenomicsGene Expression ProfilingRNA-SeqSequence Analysis, RNATranscriptomeAnimalsChromatin Immunoprecipitation SequencingHumansMice

Identifiers

What OpenQuestion 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 OpenQuestion graph.