Seq-Scope-eXpanded: spatial omics beyond optical resolution

seq-scope-expanded:-spatial-omics-beyond-optical-resolution
Seq-Scope-eXpanded: spatial omics beyond optical resolution

Data availability

The Seq-Scope-X datasets generated from this study were deposited to GEO under accession code GSE316811 and to the Deep Blue Data repository61 as raw sequences and spatially annotated digital gene expression (sDGE) matrix. Publicly available datasets used in this study include GEO accession codes GSE230402 (Bulk), GSE165141 (ST), GSE192741 (Visium), GSE169706 (Seq-ScopeMISEQ), and GSE207843 (xDBiT), as well as data available at Deep Blue Data (Seq-ScopeNOVASEQ: https://doi.org/10.7302/tw62-4f97), LISTA database (Stereo-Seq: https://db.cngb.org/stomics/lista/download/), Broad Single Cell Portal (Slide-Seq: https://singlecell.broadinstitute.org/single_cell/study/SCP354/slide-seq-study), and MERFISH Mouse Liver Map31. The source image files corresponding to all microscopy figures are available in Figshare62. The datasets used for benchmarking and distortion analyses are provided as Source Data. Source data are provided in this paper.

Code availability

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Acknowledgements

The authors thank the U-M Advanced Genomics Core (AGC) for their cooperation and help in performing Seq-Scope and sequencing analysis. We thank Lee, Han and Kang lab members for their help in experiments and analysis. The work was supported by the Taubman Institute (to H.M.K. and J.H.L.), NIH (F31AG094300 to A.A., T32AG000114 to A.A., C.S.C. and Y.S.K., UH3CA268091 and R01DK133448 to J.H.L., R01AG079163 to M.K. and J.H.L., R35GM147420 to H.-S.H., and R01HG011031 to Y.S. and H.M.K.), Chan Zuckerberg Initiative (to H.M.K.), and Glenn Foundation (to J.H.L.) grants.

Author information

Authors and Affiliations

  1. Department of Molecular & Integrative Physiology, University of Michigan, Ann Arbor, USA

    Angelo Anacleto, Anna Park, Chun-Seok Cho, Yongha Hwang, Yongsung Kim, Jer-En Hsu, Qingyang Zhao, Xiaoya Zhao, Daniel Kim, Mitchell Schrank, Myungjin Kim & Jun Hee Lee

  2. Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, USA

    Weiqiu Cheng, Yichen Si & Hyun Min Kang

  3. Department of Chemistry, University of Illinois at Urbana-Champaign, Urbana, USA

    Qianlu Feng, Alex William Schrader, Seokjin Yeo & Hee-Sun Han

  4. Neuroscience Program, University of Illinois at Urbana-Champaign, Urbana, USA

    Qianlu Feng & Hee-Sun Han

  5. Space Planning and Analysis, University of Michigan Medical School, Ann Arbor, USA

    Yongha Hwang

  6. Department of Bioengineering, University of Illinois at Urbana-Champaign, Urbana, USA

    Seokjin Yeo & Hee-Sun Han

  7. Division of Dermatology, Department of Medicine, University of California, Los Angeles, USA

    Rosane Teles & Robert L. Modlin

  8. Department of Dermatology, University of Michigan, Ann Arbor, USA

    Olesya Plazyo & Johann E. Gudjonsson

  9. Department of Pathology and Mary H. Weiser Food Allergy Center, University of Michigan, Ann Arbor, USA

    Chang H. Kim

Authors

  1. Angelo Anacleto
  2. Weiqiu Cheng
  3. Qianlu Feng
  4. Anna Park
  5. Chun-Seok Cho
  6. Yongha Hwang
  7. Yongsung Kim
  8. Yichen Si
  9. Jer-En Hsu
  10. Qingyang Zhao
  11. Xiaoya Zhao
  12. Daniel Kim
  13. Mitchell Schrank
  14. Alex William Schrader
  15. Seokjin Yeo
  16. Rosane Teles
  17. Robert L. Modlin
  18. Olesya Plazyo
  19. Johann E. Gudjonsson
  20. Myungjin Kim
  21. Chang H. Kim
  22. Hee-Sun Han
  23. Hyun Min Kang
  24. Jun Hee Lee

Contributions

A.A. conceived and designed the study, performed experiments, and developed the Seq-Scope-X methodology with guidance and mentoring from H.-S.H., H.M.K., and J.H.L. A.A., W.C., Y.H., Y.S., A.W.S., and S.Y. performed computational and statistical analyses. Q.F., A.P., C.S.C., Y.K., J.E.H., Q.Z., X.Z., D.K., and M.S. assisted with experiments. M.K. and C.H.K. contributed to data interpretation. R.T., R.L.M., O.P., J.E.G., and M.K. provided tissue samples. A.A., H.-S.H., H.M.K., and J.H.L. drafted the manuscript. All authors reviewed, edited, and approved the final manuscript.

Corresponding authors

Correspondence to Hee-Sun Han, Hyun Min Kang or Jun Hee Lee.

Ethics declarations

Competing interests

J.H.L. is an inventor on U.S. Patent No. 12,319,955, filed by The Regents of the University of Michigan, which covers the Seq-Scope method for localized detection of nucleic acids in tissue samples as described in this manuscript. Y.H. is currently an employee of Samsung Semiconductor. All other authors declare no competing interests.

Peer review

Peer review information

Nature Communications thanks Zhangsheng Yu, who co-reviewed with Zhouhui Qi and Xin Yuan, Christoph Ziegenhain, and the other anonymous reviewer(s) for their contribution to the peer review of this work. A peer review file is available.

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Anacleto, A., Cheng, W., Feng, Q. et al. Seq-Scope-eXpanded: spatial omics beyond optical resolution. Nat Commun (2026). https://doi.org/10.1038/s41467-026-69346-8

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  • DOI: https://doi.org/10.1038/s41467-026-69346-8