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.
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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.
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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
