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Peer-Reviewed Publication
Nat Methods2026January 15, 2026Journal Article

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

Archibald Enninful1, Zhaojun Zhang2, Dmytro Klymyshyn3, Matthew Ingalls4, Mingyu Yang1, Hailing Zong3, Zhiliang Bai1, Negin Farzad1, Graham Su1, Alev Baysoy1, Jungmin Nam1, Yao Lu1, Shuozhen Bao1, Siyan Deng1, Nancy R Zhang2, Oliver Braubach4, Mina L Xu5, Zongming Ma6, Rong Fan7,8,9,10,11
1Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
2Department of Statistics and Data Science, The Wharton School, University of Pennsylvania, Philadelphia, PA, USA.
3Akoya Biosciences, Menlo Park, CA, USA.
4Bruker Spatial Biology, St Louis, MO, USA.
5Department of Pathology, Yale School of Medicine, New Haven, CT, USA. mina.xu@yale.edu.
6Department of Statistics and Data Science, Yale University, New Haven, CT, USA. zongming.ma@yale.edu.
7Department of Biomedical Engineering, Yale University, New Haven, CT, USA. rong.fan@yale.edu.
8Department of Pathology, Yale School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.
9Yale Stem Cell Center and Yale Cancer Center, Yale School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.
10Human and Translational Immunology Program, Yale School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.
11Yale Center for Research on Aging (Y-Age), Yale School of Medicine, New Haven, CT, USA. rong.fan@yale.edu.

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 bot…

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