Evidence map›Paper›PMID 40624052›Full record

ArticleNature communications2025

Automated cell annotation and classification on histopathology for spatial biomarker discovery.

Zhe Li, Seyed Hossein Mirjahanmardi, Rasoul Sali, Feyisope Eweje, Matthew Gopaulchan, Leon Kloker, Xiaoming Zhang, Guoxin Li, Yuming Jiang, Ruijiang Li

Abstract read
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed.

  1. Article
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  4. Review
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  10. Laser capture microdissection.Nature reviews. Methods primers · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Zhe Li *Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-0105-6351
Seyed Hossein Mirjahanmardi *Department of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Rasoul SaliDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Feyisope EwejeDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Matthew GopaulchanDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA.
Leon KlokerInstitute for Computational & Mathematical Engineering, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-8665-3840
Xiaoming ZhangDepartment of Pathology, Stanford University School of Medicine, Stanford, CA, USA.
Guoxin LiDepartment of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, China.ORCID http://orcid.org/0000-0003-2773-7048
Yuming JiangDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. yumjiang@wakehealth.edu.ORCID http://orcid.org/0000-0001-6184-3931
Ruijiang LiDepartment of Radiation Oncology, Stanford University School of Medicine, Stanford, CA, USA. rli2@stanford.edu.ORCID http://orcid.org/0000-0002-0232-5998

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Histopathology with hematoxylin and eosin (H&E) staining is routinely employed for clinical diagnoses. Single-cell analysis of histopathology provides a powerful tool for understanding the intricate cellular interactions underlying disease progression and therapeutic response. However, existing efforts are hampered by inefficient and error-prone human annotations. Here, we present an experimental and computational approach for automated cell annotation and classification on H&E-stained images. Instead of human annotations, we use multiplexed immunofluorescence (mIF) to define cell types based on cell lineage protein markers. By co-registering H&E images with mIF of the same tissue section at the single-cell level, we create a dataset of 1,127,252 cells with high-quality annotations on tissue microarray cores. A deep learning model combining self-supervised learning with domain adaptation is trained to classify four cell types on H&E images with an overall accuracy of 86%-89%, and the cell classification model is applicable to whole slide images. Further, we show that spatial interactions among specific immune cells in the tumor microenvironment are linked to patient survival and response to immune checkpoint inhibitors. Our work provides a scalable approach for single-cell analysis of standard histopathology and may enable discovery of novel spatial biomarkers for precision oncology.

Indexed as

Biomarkers, TumorNeoplasmsSingle-Cell AnalysisBiomarkersDeep LearningFluorescent Antibody TechniqueHumansTissue Array AnalysisTumor MicroenvironmentBiomarkersBiomarkers, Tumor

Identifiers

PMID40624052
PMCPMC12234899

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.