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Record W4415814107 · doi:10.1038/s41467-025-65783-z

AI-powered spatial cell phenomics enhances risk stratification in non-small cell lung cancer

2025· article· en· W4415814107 on OpenAlexfundno aff
Simon Schallenberg, Gabriel Dernbach, Sharon Ruane, Philipp Jurmeister, Cornelius Böhm, Kai Standvoss, Marco Frentsch, Mihnea P. Dragomir, Philipp Keyl, Corinna Friedrich, Il‐Kang Na, Sabine Merkelbach‐Bruse, Alexander Quaas, Nikolaj Frost, Kyrill Boschung, Winfried Randerath, Georg Schlachtenberger, Matthias Heldwein, Ulrich Keilholz, Khosro Hekmat, Jens‐Carsten Rückert, Reinhard Büttner, Angela Vasaturo, David Horst, Lukas Ruff, Maximilian Alber, Klaus-Robert Müller, Frederick Klauschen

Bibliographic record

VenueNature Communications · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicSingle-cell and spatial transcriptomics
Canadian institutionsnot available
FundersBerlin Center for Machine LearningBanting and Best Diabetes Centre, University of TorontoBundesministerium für Bildung und ForschungBerlin Institute of HealthInstitute for Information and Communications Technology PromotionDeutschen Konsortium für Translationale KrebsforschungKorea UniversityMinistry of Science and ICT, South Korea
KeywordsLung cancerRisk stratificationTumor microenvironmentCellCancerImmune systemAdenocarcinomaMultiplex

Abstract

fetched live from OpenAlex

Risk stratification remains a critical challenge in non-small cell lung cancer patients for optimal therapy selection. In this study, we develop an artificial intelligence-powered spatial cellomics approach that combines histology, multiplex immunofluorescence imaging and multimodal machine learning to characterize the complex cellular relationships of 43 cell phenotypes in the tumor microenvironment in a real-world retrospective cohort of 1168 non-small cell lung cancer patients from two large German cancer centers. The model identifies cell niches associated with survival and achieves a 14% and 47% improvement in risk stratification in the two main non-small cell lung cancer subtypes, lung adenocarcinoma and squamous cell carcinoma, respectively, combining niche patterns with conventional cancer staging. Our results show that complex immune cell niche patterns identify potentially undertreated high-risk patients qualifying for adjuvant therapy. Our approach highlights the potential of artificial intelligence powered multiplex imaging analyses to better understand the contribution of the tumor microenvironment to cancer progression and to improve risk stratification and treatment selection in non-small cell lung cancer.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.003
Threshold uncertainty score0.006

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.000
Scholarly communication0.0010.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.008
GPT teacher head0.274
Teacher spread0.266 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations9
Published2025
Admission routes1
Has abstractyes

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