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PreprintCC BY-NC-NDbioRxiv

MCseg: AI agent-guided workflow search for no-code cell segmentation and transcript attribution in spatial transcriptomics

  1. 1Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei 106, Taiwan

Abstract

Cell-level analysis of high-resolution spatial transcriptomics depends on accurate segmentation and transcript assignment, yet current workflows often trade transcript capture for boundary purity and can require substantial image-analysis expertise. We developed MCseg, a downloadable no-code platform whose fixed segmentation engine was derived by an AI-agent-guided search in which an AI agent iteratively proposed and evaluated combinations of image-processing and segmentation operations against Xenium-derived cell boundaries. In a lung adenocarcinoma development set, fixed-parameter MCseg increased mean panoptic quality from 0.432 to 0.472 relative to an Optuna-tuned two-diameter Cellpose baseline, while a reference-guided calibration analysis reached 0.554. In an independent expert-annotated colorectal cancer region, MCseg showed higher lineage recall and micro-F1 than the StarDist-based ENACT workflow among cells covered by both methods. Across 15 colorectal cancer regions, MCseg increased neighborhood expression discordance and reduced lineage-exclusive co-expression relative to Space Ranger at similar UMI density. The fixed workflow also transferred to fresh-frozen breast cancer without tissue-specific architecture search, illustrating an agent-guided route to reproducible, locally deployable cell-level spatial transcriptomic analysis.

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BibTeX
@misc{chan2026mcseg,
  title = {{MCseg: AI agent-guided workflow search for no-code cell segmentation and transcript attribution in spatial transcriptomics}},
  author = {C.-R. Chan and N.-W. Chang and C.-Y. Wang and H.-Y. Tan and S.-J. Lin},
  howpublished = {bioRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.20.752837},
  url = {https://www.biorxiv.org/content/10.64898/2026.09.20.752837v1},
  note = {CC BY-NC-ND},
}
RIS
TY  - UNPB
TI  - MCseg: AI agent-guided workflow search for no-code cell segmentation and transcript attribution in spatial transcriptomics
AU  - C.-R. Chan
AU  - N.-W. Chang
AU  - C.-Y. Wang
AU  - H.-Y. Tan
AU  - S.-J. Lin
PY  - 2026
DA  - 2026/09/20
PB  - bioRxiv
DO  - 10.64898/2026.09.20.752837
UR  - https://www.biorxiv.org/content/10.64898/2026.09.20.752837v1
AB  - Cell-level analysis of high-resolution spatial transcriptomics depends on accurate segmentation and transcript assignment, yet current workflows often trade transcript capture for boundary purity and can require substantial image-analysis expertise. We developed MCseg, a downloadable no-code platform whose fixed segmentation engine was derived by an AI-agent-guided search in which an AI agent iteratively proposed and evaluated combinations of image-processing and segmentation operations against Xenium-derived cell boundaries. In a lung adenocarcinoma development set, fixed-parameter MCseg increased mean panoptic quality from 0.432 to 0.472 relative to an Optuna-tuned two-diameter Cellpose baseline, while a reference-guided calibration analysis reached 0.554. In an independent expert-annotated colorectal cancer region, MCseg showed higher lineage recall and micro-F1 than the StarDist-based ENACT workflow among cells covered by both methods. Across 15 colorectal cancer regions, MCseg increased neighborhood expression discordance and reduced lineage-exclusive co-expression relative to Space Ranger at similar UMI density. The fixed workflow also transferred to fresh-frozen breast cancer without tissue-specific architecture search, illustrating an agent-guided route to reproducible, locally deployable cell-level spatial transcriptomic analysis.
ER  -