Cross-species molecular stratification enables T cell receptor diagnosis of Parkinson's disease.
6 affiliations
- 1Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China.
- 2Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. [email protected].
- 3School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China. [email protected].
- 4School of Medicine, Nanjing University of Chinese Medicine, Nanjing, China.
- 5Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
- 6Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, School of Basic Medical Sciences, Nanjing Medical University, Nanjing, China. [email protected].
Abstract
Background
Developing peripheral blood-based diagnostic models for idiopathic Parkinson's disease (iPD), particularly those leveraging the T-cell receptor (TCR) repertoire, has long been considered infeasible because patient-derived TCRs appear to lack convergent sequence motifs. We reasoned that this apparent absence of shared TCR features likely reflects both insufficient sample sizes and unaccounted immune heterogeneity within the iPD population.Methods
We reconstructed TCR repertoires from the two largest iPD cohorts currently available, anchoring them with three mechanistically distinct mouse models to stratify patients into model-anchored informed subtypes. Within these data-driven subtypes, we trained subtype-specific, multimodal multi-instance classifiers.Results
We demonstrated that iPD patients can be successfully stratified into model-anchored informed subtypes. Furthermore, the trained subtype-specific, multimodal multi-instance classifiers achieved an Area Under Curve (AUC) exceeding 0.8 for both subtypes.Conclusions
Our findings underscore the critical role of disease stratification in enabling TCR repertoire-based modeling in neurodegenerative diseases.
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BibTeX
@article{chen2026crossspecies,
title = {{Cross-species molecular stratification enables T cell receptor diagnosis of Parkinson's disease.}},
author = {Jiayu Chen and Xian Xia and Yuruo Zhang and Xiaoge Tong and Yue Liang and Xiangding Fan and Qinghao Meng and Yihong Wei and Gang Hu},
journal = {Genome medicine},
year = {2026},
month = sep,
doi = {10.1186/s13073-026-01776-x},
url = {https://europepmc.org/article/MED/42907884},
note = {CC BY},
}
RIS
TY - JOUR
TI - Cross-species molecular stratification enables T cell receptor diagnosis of Parkinson's disease.
AU - Jiayu Chen
AU - Xian Xia
AU - Yuruo Zhang
AU - Xiaoge Tong
AU - Yue Liang
AU - Xiangding Fan
AU - Qinghao Meng
AU - Yihong Wei
AU - Gang Hu
PY - 2026
DA - 2026/09/01
JO - Genome medicine
DO - 10.1186/s13073-026-01776-x
UR - https://europepmc.org/article/MED/42907884
AB - Background Developing peripheral blood-based diagnostic models for idiopathic Parkinson's disease (iPD), particularly those leveraging the T-cell receptor (TCR) repertoire, has long been considered infeasible because patient-derived TCRs appear to lack convergent sequence motifs. We reasoned that this apparent absence of shared TCR features likely reflects both insufficient sample sizes and unaccounted immune heterogeneity within the iPD population.Methods We reconstructed TCR repertoires from the two largest iPD cohorts currently available, anchoring them with three mechanistically distinct mouse models to stratify patients into model-anchored informed subtypes. Within these data-driven subtypes, we trained subtype-specific, multimodal multi-instance classifiers.Results We demonstrated that iPD patients can be successfully stratified into model-anchored informed subtypes. Furthermore, the trained subtype-specific, multimodal multi-instance classifiers achieved an Area Under Curve (AUC) exceeding 0.8 for both subtypes.Conclusions Our findings underscore the critical role of disease stratification in enabling TCR repertoire-based modeling in neurodegenerative diseases.
SN - 1756-994X
ER -