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使用ePytope-TCR对T细胞受体-表位预测器进行基准测试。

Benchmarking of T cell receptor-epitope predictors with ePytope-TCR.

作者信息

Drost Felix, Chernysheva Anna, Albahah Mahmoud, Kocher Katharina, Schober Kilian, Schubert Benjamin

机构信息

Computational Health Center, Helmholtz Munich, 85764 Neuherberg, Germany; School of Life Sciences Weihenstephan, Technical University of Munich, 85354 Freising, Germany.

Computational Health Center, Helmholtz Munich, 85764 Neuherberg, Germany.

出版信息

Cell Genom. 2025 Jun 27:100946. doi: 10.1016/j.xgen.2025.100946.


DOI:10.1016/j.xgen.2025.100946
PMID:40628266
Abstract

Understanding the recognition of disease-derived epitopes through T cell receptors (TCRs) has the potential to serve as a stepping stone for the development of efficient immunotherapies and vaccines. While a plethora of sequence-based prediction methods for TCR-epitope binding exists, their pre-trained models have not been comparatively evaluated. To alleviate this shortcoming, we integrated 21 TCR-epitope prediction models into the immune-prediction framework ePytope, offering interoperable interfaces with standard TCR repertoire data formats. We showcase the applicability of ePytope-TCR by evaluating the performance of these publicly available prediction models on two challenging datasets. While novel predictors successfully predicted binding to frequently observed epitopes, all methods failed for less frequently observed epitopes. Further, we detected a strong bias in the prediction scores between different epitope classes. We envision this benchmark to guide researchers in their choice of a predictor and to accelerate the method development by defining standardized evaluation settings.

摘要

了解通过T细胞受体(TCR)识别疾病衍生表位有潜力成为开发高效免疫疗法和疫苗的垫脚石。虽然存在大量基于序列的TCR-表位结合预测方法,但它们的预训练模型尚未得到比较评估。为了弥补这一不足,我们将21个TCR-表位预测模型集成到免疫预测框架ePytope中,提供与标准TCR库数据格式的可互操作接口。我们通过在两个具有挑战性的数据集上评估这些公开可用预测模型的性能,展示了ePytope-TCR的适用性。虽然新型预测器成功预测了与常见表位的结合,但所有方法在较少见表位上均失败。此外,我们检测到不同表位类别之间的预测分数存在强烈偏差。我们期望这个基准能够指导研究人员选择预测器,并通过定义标准化评估设置来加速方法开发。

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Benchmarking of T cell receptor-epitope predictors with ePytope-TCR.

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引用本文的文献

[1]
Predicting TCR-epitope recognition: How good are we?

Cell Genom. 2025-8-13

[2]
Comprehensive epitope mutational scan database enables accurate T cell receptor cross-reactivity prediction.

bioRxiv. 2025-2-21

本文引用的文献

[1]
Predicting T cell receptor functionality against mutant epitopes.

Cell Genom. 2024-9-11

[2]
TULIP: A transformer-based unsupervised language model for interacting peptides and T cell receptors that generalizes to unseen epitopes.

Proc Natl Acad Sci U S A. 2024-6-11

[3]
Deep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells.

Nat Commun. 2024-4-13

[4]
Adaptive immune responses are larger and functionally preserved in a hypervaccinated individual.

Lancet Infect Dis. 2024-5

[5]
Enhancing TCR specificity predictions by combined pan- and peptide-specific training, loss-scaling, and sequence similarity integration.

Elife. 2024-3-4

[6]
BERTrand-peptide:TCR binding prediction using Bidirectional Encoder Representations from Transformers augmented with random TCR pairing.

Bioinformatics. 2023-8-1

[7]
iTCep: a deep learning framework for identification of T cell epitopes by harnessing fusion features.

Front Genet. 2023-5-9

[8]
Recruitment of epitope-specific T cell clones with a low-avidity threshold supports efficacy against mutational escape upon re-infection.

Immunity. 2023-6-13

[9]
Performance comparison of TCR-pMHC prediction tools reveals a strong data dependency.

Front Immunol. 2023

[10]
epiTCR: a highly sensitive predictor for TCR-peptide binding.

Bioinformatics. 2023-5-4

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