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TCRpred:纳入T细胞受体库以预测临床结果。

TCRpred: incorporating T-cell receptor repertoire for clinical outcome prediction.

作者信息

Liu Meiling, Liu Yang, Hsu Li, He Qianchuan

机构信息

Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, United States.

Department of Mathematics and Statistics, Wright State University, Dayton, OH, United States.

出版信息

Front Genet. 2024 Mar 13;15:1345559. doi: 10.3389/fgene.2024.1345559. eCollection 2024.

DOI:10.3389/fgene.2024.1345559
PMID:38544800
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10965803/
Abstract

T-cell receptor (TCR) plays critical roles in recognizing antigen peptides and mediating adaptive immune response against disease. High-throughput technologies have enabled the sequencing of TCR repertoire at the single nucleotide level, allowing researchers to characterize TCR sequences with high resolutions. The TCR sequences provide important information about patients' adaptive immune system, and have the potential to improve clinical outcome prediction. However, it is challenging to incorporate the TCR repertoire data for prediction, because the data is unstructured, highly complex, and TCR sequences vary widely in their compositions and abundances across different individuals. We introduce TCRpred, an analytic tool for incorporating TCR repertoire for clinical outcome prediction. The TCRpred is able to utilize features that can be extracted from the TCR amino acid sequences, as well as features that are hidden in the TCR amino acid sequences and are hard to extract. Simulation studies show that the proposed approach has a good performance in predicting clinical outcome and tends to be more powerful than potential alternative approaches. We apply the TCRpred to real cancer datasets and demonstrate its practical utility in clinical outcome prediction.

摘要

T细胞受体(TCR)在识别抗原肽和介导针对疾病的适应性免疫反应中发挥着关键作用。高通量技术已能够在单核苷酸水平上对TCR库进行测序,使研究人员能够以高分辨率表征TCR序列。TCR序列提供了有关患者适应性免疫系统的重要信息,并有可能改善临床结果预测。然而,将TCR库数据纳入预测具有挑战性,因为数据是非结构化的、高度复杂的,并且TCR序列在不同个体之间的组成和丰度差异很大。我们引入了TCRpred,这是一种用于将TCR库纳入临床结果预测的分析工具。TCRpred能够利用可从TCR氨基酸序列中提取的特征,以及隐藏在TCR氨基酸序列中且难以提取的特征。模拟研究表明,所提出的方法在预测临床结果方面具有良好的性能,并且往往比潜在的替代方法更强大。我们将TCRpred应用于真实的癌症数据集,并证明了其在临床结果预测中的实际效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/cfc3e423b2db/fgene-15-1345559-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/e4112adf43ee/fgene-15-1345559-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/bcf49c87abb2/fgene-15-1345559-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/cfc3e423b2db/fgene-15-1345559-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/e4112adf43ee/fgene-15-1345559-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/bcf49c87abb2/fgene-15-1345559-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/eb6c/10965803/cfc3e423b2db/fgene-15-1345559-g003.jpg

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1
TCRpred: incorporating T-cell receptor repertoire for clinical outcome prediction.TCRpred:纳入T细胞受体库以预测临床结果。
Front Genet. 2024 Mar 13;15:1345559. doi: 10.3389/fgene.2024.1345559. eCollection 2024.
2
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本文引用的文献

1
Can we predict T cell specificity with digital biology and machine learning?我们能否通过数字生物学和机器学习来预测 T 细胞特异性?
Nat Rev Immunol. 2023 Aug;23(8):511-521. doi: 10.1038/s41577-023-00835-3. Epub 2023 Feb 8.
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From thymus to tissues and tumors: A review of T-cell biology.从胸腺到组织和肿瘤:T 细胞生物学综述。
J Allergy Clin Immunol. 2023 Jan;151(1):81-97. doi: 10.1016/j.jaci.2022.10.011. Epub 2022 Oct 19.
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TCR-L: an analysis tool for evaluating the association between the T-cell receptor repertoire and clinical phenotypes.
TCR-L:一种用于评估 T 细胞受体库与临床表型之间关联的分析工具。
BMC Bioinformatics. 2022 Apr 28;23(1):152. doi: 10.1186/s12859-022-04690-2.
4
Cancer Therapy With TCR-Engineered T Cells: Current Strategies, Challenges, and Prospects.T 细胞受体工程化 T 细胞治疗癌症:当前策略、挑战与展望。
Front Immunol. 2022 Mar 3;13:835762. doi: 10.3389/fimmu.2022.835762. eCollection 2022.
5
T cell receptor (TCR) signaling in health and disease.T 细胞受体 (TCR) 在健康和疾病中的信号转导。
Signal Transduct Target Ther. 2021 Dec 13;6(1):412. doi: 10.1038/s41392-021-00823-w.
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Multiomics Analysis Reveals Distinct Immunogenomic Features of Lung Cancer with Ground-Glass Opacity.多组学分析揭示了具有磨玻璃密度的肺癌的独特免疫基因组特征。
Am J Respir Crit Care Med. 2021 Nov 15;204(10):1180-1192. doi: 10.1164/rccm.202101-0119OC.
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Dynamic changes in the T cell receptor repertoire during treatment with radiotherapy combined with an immune checkpoint inhibitor.放疗联合免疫检查点抑制剂治疗过程中 T 细胞受体库的动态变化。
Mol Oncol. 2021 Nov;15(11):2958-2968. doi: 10.1002/1878-0261.13082. Epub 2021 Sep 1.
8
The T cell receptor repertoire of tumor infiltrating T cells is predictive and prognostic for cancer survival.肿瘤浸润 T 细胞的 T 细胞受体谱可预测和预测癌症的生存情况。
Nat Commun. 2021 Jul 2;12(1):4098. doi: 10.1038/s41467-021-24343-x.
9
Tertiary lymphoid structure score: a promising approach to refine the TNM staging in resected non-small cell lung cancer.三级淋巴结构评分:一种有前途的方法,可细化切除的非小细胞肺癌的 TNM 分期。
Br J Cancer. 2021 May;124(10):1680-1689. doi: 10.1038/s41416-021-01307-y. Epub 2021 Mar 15.
10
DeepTCR is a deep learning framework for revealing sequence concepts within T-cell repertoires.DeepTCR 是一个深度学习框架,用于揭示 T 细胞受体库中的序列概念。
Nat Commun. 2021 Mar 11;12(1):1605. doi: 10.1038/s41467-021-21879-w.