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PreprintCC BY-NDbioRxiv

Agentic AI enables cell segmentation-free cell-type inference and cell-type-guided cell segmentation in spatial transcriptomics

1 more authors
  1. 1Pusan National University

Abstract

Cell-type identification in spatial transcriptomics often relies on cell segmentation, which can introduce inaccuracies in cell boundaries and transcript assignment. Segmentation-free or cell-free methods have been developed to completely avoid cell segmentation, but inaccurate cell typing hinder accurate downstream analysis. Here, we introduce SSAF-T, a segmentation-free agentic framework that identifies cell types directly from spatial gene expression without predefined reference datasets. For the reference-free cell typing, SSAF-T incorporates CeLLMan, which employs expert-level agents for each organ to annotate cell types using a literature-grounded knowledge graph. We benchmark SSAF-T on both array-based and imaging-based spatial transcriptomics datasets in terms of accuracy, reproducibility, and scalability. We further show that SSAF-T provides an accurate cell segmentation based on the segmentation-free mapping, which ensure compatibility to existing downstream analysis ecosystem, and eventually enable quantitative analysis at single-cell level.

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BibTeX
@misc{jeong2026agentic,
  title = {{Agentic AI enables cell segmentation-free cell-type inference and cell-type-guided cell segmentation in spatial transcriptomics}},
  author = {Y. Jeong and H. Lee and D. Lee and H.-M. Kim and S.-H. Kim and S. Park and J. Bae and E. S. Cho and Y.-L. Choi and O. Kwon and J.-I. Kim and H. Lee and J. Park},
  howpublished = {bioRxiv},
  year = {2026},
  month = nov,
  doi = {10.64898/2026.11.05.764509},
  url = {https://www.biorxiv.org/content/10.64898/2026.11.05.764509v1},
  note = {CC BY-ND},
}
RIS
TY  - UNPB
TI  - Agentic AI enables cell segmentation-free cell-type inference and cell-type-guided cell segmentation in spatial transcriptomics
AU  - Y. Jeong
AU  - H. Lee
AU  - D. Lee
AU  - H.-M. Kim
AU  - S.-H. Kim
AU  - S. Park
AU  - J. Bae
AU  - E. S. Cho
AU  - Y.-L. Choi
AU  - O. Kwon
AU  - J.-I. Kim
AU  - H. Lee
AU  - J. Park
PY  - 2026
DA  - 2026/11/05
PB  - bioRxiv
DO  - 10.64898/2026.11.05.764509
UR  - https://www.biorxiv.org/content/10.64898/2026.11.05.764509v1
AB  - Cell-type identification in spatial transcriptomics often relies on cell segmentation, which can introduce inaccuracies in cell boundaries and transcript assignment. Segmentation-free or cell-free methods have been developed to completely avoid cell segmentation, but inaccurate cell typing hinder accurate downstream analysis. Here, we introduce SSAF-T, a segmentation-free agentic framework that identifies cell types directly from spatial gene expression without predefined reference datasets. For the reference-free cell typing, SSAF-T incorporates CeLLMan, which employs expert-level agents for each organ to annotate cell types using a literature-grounded knowledge graph. We benchmark SSAF-T on both array-based and imaging-based spatial transcriptomics datasets in terms of accuracy, reproducibility, and scalability. We further show that SSAF-T provides an accurate cell segmentation based on the segmentation-free mapping, which ensure compatibility to existing downstream analysis ecosystem, and eventually enable quantitative analysis at single-cell level.
ER  -