🔬 IN-DEPTH
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The advent of spatial transcriptomics and spatial proteomics have enabled profound insights into tissue organization and provided systems-level understanding of diseases. However, both technologies remain largely independent, and emerging same slide spatial multi-omics approaches are generally limited in plex spatial resolution, and analysis approaches. We introduce IN-situ DEtailed Phenotyping To High-resolution transcriptomics (IN-DEPTH), a streamlined and resource-effective approach compatible with various spatial platforms. This iterative approach first entails single-cell spatial proteomics and rapid analysis to guide subsequent spatial transcriptomics capture on the same slide without loss in RNA signal. We also introduce k-bandlimited Spectral Graph Cross-Correlation (SGCC) to facilitate additional insights through integrative spatial multi-omics analysis. Application of IN-DEPTH and SGCC on lymphoid tissues demonstrated precise single-cell phenotyping and cell-type specific transcriptome capture, and accurately resolved the local and global transcriptome changes associated with the cellular organization of germinal centers. We then implemented IN-DEPTH and SGCC to dissect the tumor microenvironment (TME) of Epstein-Barr Virus (EBV)-positive and EBV-negative diffuse large B-cell lymphoma (DLBCL). Our results identified a key tumor-macrophage-CD4 T-cell immunomodulatory axis differently regulated between EBV-positive and EBV-negative DLBCL, and its central role in coordinating immune dysfunction and suppression. IN-DEPTH enables scalable, resource-efficient, and comprehensive spatial multi-omics dissection of tissues to advance clinically relevant discoveries.
Reference
If you use IN-DEPTH in your research, please cite:
📎 BibTeX (click to expand)
@article{yiu2026indepth,
title={Same-Slide Spatial Multi-Omics Integration with IN-DEPTH Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment},
author={Yiu, Stephanie Pei Tung and Chang, Yuzhou and Yeo, Yao Yu and Qiu, Huaying and Wu, Wenrui and Michel, Hendrik A and Jin, Xiaojie and Huang, Rongting and Kure, Shoko and Parmelee, Lindsay and Luo, Shuli and Cramer, Precious and Lee, Jia Le and Wang, Yang and Zhao, Zhangxin and Yeung, Jason and El Ahmar, Nourhan and Simsek, Berkay and Mohanna, Razan and Van Orden, McKayla and Lu, Wesley S and Livak, Kenneth J and Li, Shuqiang and Gao, Ce and Burgess, Melinda and Keane, Colm and Shahryari, Jahanbanoo and Kingsley, Leandra G and Al-Humadi, Reem N and Nasr, Sahar and Nkosi, Dingani and Sadigh, Sam and Rock, Philip and Frauenfeld, Leonie and Kaufmann, Louisa and Zhu, Bokai and Basak, Ankit and Dhanikonda, Nagendra and Chan, Chi Ngai and Krull, Jordan and Cho, Ye Won and Chen, Chia-Yu and Brown, Jonathan and Wang, Hongbo and Zhao, Bo and Lee, Jia-Ying Joey and Loo, Lit-Hsin and Kim, David M and Boussiotis, Vassiliki A and Zhang, Baochun and Wei, Kevin and Shalek, Alex K and Howitt, Brooke E and Signoretti, Sabina and Sch{\"u}rch, Christian M and Hodi, F Stephen and Burack, W Richard and Rodig, Scott J and Ma, Qin and Jiang, Sizun},
journal={Cancer Discovery},
year={2026},
doi={10.1158/2159-8290.CD-25-0775},
pmid={41874448},
publisher={American Association for Cancer Research}
}
Yiu SP†, Chang Y†, Yeo YY†, Qiu H†, Wu W†, Michel HA, Jin X, Huang R, Kure S, Parmelee L, Luo S, Cramer P, Lee JL, Wang Y, Zhao Z, Yeung J, El Ahmar N, Simsek B, Mohanna R, Van Orden M, Lu WS, Livak KJ, Li S, Gao C, Burgess M, Keane C, Shahryari J, Kingsley LG, Al-Humadi RN, Nasr S, Nkosi D, Sadigh S, Rock P, Frauenfeld L, Kaufmann L, Zhu B, Basak A, Dhanikonda N, Chan CN, Krull J, Cho YW, Chen CY, Brown J, Wang H, Zhao B, Lee JYJ, Loo LH, Kim DM, Boussiotis VA, Zhang B, Wei K, Shalek AK, Howitt BE, Signoretti S, Schürch CM, Hodi FS, Burack WR, Rodig SJ, Ma Q#, Jiang S#⁺. Same-Slide Spatial Multi-Omics Integration with IN-DEPTH Reveals Tumor Virus-Linked Spatial Reorganization of the Tumor Microenvironment. Cancer Discovery. 2026. doi: 10.1158/2159-8290.CD-25-0775. PMID: 41874448.
† These authors contributed equally.
# Senior authors.
Corresponding Author:
Sizun Jiang | 3 Blackfan Circle, CLS 1034, Boston, MA 02115, USA
Email: sjiang3@bidmc.harvard.edu
Keywords
| Spatial multi-omics | Spatial proteomics | Spatial transcriptomics | Graph signal processing | Computational biology | Tumor microenvironment | EBV | DLBCL | Systems immunology |