scTIME: single-cell-informed interpretable modeling of immunotherapy-associated immune states in non-small cell lung cancer.
- 1YongJia People's Hospital, Wenzhou, China.
- 2Shanxi Acupuncture Hospital, Taiyuan, China.
- 3Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Abstract
Immune checkpoint inhibitor response in non-small cell lung cancer (NSCLC) reflects coordinated tumor and immune states that are not fully captured by single biomarkers. We developed scTIME, an interpretable model that translates single-cell immune programs into bulk transcriptomic scores, and integrated public single-cell, T-cell receptor, transcriptomic, survival, and proteogenomic cohorts. Response modeling used two cohorts with different endpoints (40 patients) and compared six algorithms. ElasticNet was selected as a sparse reporting model, achieving a pooled five-fold out-of-fold ROC-AUC of 0.810; nested model selection yielded 0.772. Matched held-out stratification identified response-enriched scTIME groups in a direct descriptive comparison with CD274, while the fitted score emphasized cytotoxic CD8, natural killer, SPP1 macrophage, interferon-response, and antigen-presentation programs. Single-cell analyses and external projections linked these programs to CXCL10-CXCR3 recruitment, exclusion-associated states, and T-cell receptor ecology across molecular contexts. Exploratory survival and cross-omics analyses extended the framework beyond the response cohorts but were interpreted as projection rather than independent validation. Together, the results show how cell-resolved immune biology can support transparent, multi-omic biomarker development without reducing response to a single pathway. scTIME remains exploratory because model choice was post hoc, cohorts were small and clinically heterogeneous, and endpoint-matched external validation was unavailable.
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BibTeX
@article{chen2026sctime,
title = {{scTIME: single-cell-informed interpretable modeling of immunotherapy-associated immune states in non-small cell lung cancer.}},
author = {Guozhi Chen and Chenqiu You and Hong Gao and Chengjie Xu},
journal = {Frontiers in artificial intelligence},
year = {2026},
month = oct,
doi = {10.3389/frai.2026.1918104},
url = {https://europepmc.org/article/MED/42903172},
note = {CC BY},
}
RIS
TY - JOUR
TI - scTIME: single-cell-informed interpretable modeling of immunotherapy-associated immune states in non-small cell lung cancer.
AU - Guozhi Chen
AU - Chenqiu You
AU - Hong Gao
AU - Chengjie Xu
PY - 2026
DA - 2026/10/06
JO - Frontiers in artificial intelligence
DO - 10.3389/frai.2026.1918104
UR - https://europepmc.org/article/MED/42903172
AB - Immune checkpoint inhibitor response in non-small cell lung cancer (NSCLC) reflects coordinated tumor and immune states that are not fully captured by single biomarkers. We developed scTIME, an interpretable model that translates single-cell immune programs into bulk transcriptomic scores, and integrated public single-cell, T-cell receptor, transcriptomic, survival, and proteogenomic cohorts. Response modeling used two cohorts with different endpoints (40 patients) and compared six algorithms. ElasticNet was selected as a sparse reporting model, achieving a pooled five-fold out-of-fold ROC-AUC of 0.810; nested model selection yielded 0.772. Matched held-out stratification identified response-enriched scTIME groups in a direct descriptive comparison with CD274, while the fitted score emphasized cytotoxic CD8, natural killer, SPP1 macrophage, interferon-response, and antigen-presentation programs. Single-cell analyses and external projections linked these programs to CXCL10-CXCR3 recruitment, exclusion-associated states, and T-cell receptor ecology across molecular contexts. Exploratory survival and cross-omics analyses extended the framework beyond the response cohorts but were interpreted as projection rather than independent validation. Together, the results show how cell-resolved immune biology can support transparent, multi-omic biomarker development without reducing response to a single pathway. scTIME remains exploratory because model choice was post hoc, cohorts were small and clinically heterogeneous, and endpoint-matched external validation was unavailable.
SN - 2624-8212
ER -