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T 细胞受体库特异性的定量注释。

Quantitative annotations of T-Cell repertoire specificity.

机构信息

Department of Computer Science, City University of Hong Kong, 83 Tat Tree Ave, Kowloon Tong, Hong Kong, China.

Department of Biomedical Engineering, City University of Hong Kong, 83 Tat Tree Ave, Kowloon Tong, Hong Kong, China.

出版信息

Brief Bioinform. 2023 May 19;24(3). doi: 10.1093/bib/bbad175.

Abstract

The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modeled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. We created deep-learning-based, epitope-aware vector embeddings to infer individual TCR specificity. Then we aggregated clonotype frequencies of TCRs to obtain a quantitative profile of repertoire specificity at epitope, antigen and organism levels. Applying TCRanno to 4195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, supporting the possibility of abortive infections. TCRanno discovered age-accumulated fraction of severe acute respiratory syndrome coronavirus 2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of coronavirus disease 2019. TCRanno also identified the encounter of Hepatitis B antigens as a potential trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest.

摘要

T 细胞受体 (TCR) 库的特异性决定了个性化的免疫能力。现有的方法已经对 TCR 特异性的定性方面进行了建模,而定量方面仍未得到解决。我们开发了一个名为 TCRanno 的软件包,用于量化 TCR 库的特异性。我们创建了基于深度学习的、表位感知的向量嵌入,以推断个体 TCR 的特异性。然后,我们聚合了 TCR 的克隆型频率,以获得在表位、抗原和生物体水平上的 TCR 库特异性的定量特征。将 TCRanno 应用于 4195 个 TCR 库,揭示了感染、自身免疫和癌症时 TCR 库特异性的定量变化。具体来说,TCRanno 在血清阴性的健康个体中发现了巨细胞病毒特异性的 TCR,支持了潜伏感染的可能性。TCRanno 在大流行前的样本中发现了与严重急性呼吸综合征冠状病毒 2 特异性 TCR 相关的年龄累积分数,这可能解释了 2019 年冠状病毒病的侵袭性症状和与年龄相关的严重程度。TCRanno 还发现乙型肝炎抗原的接触可能是系统性红斑狼疮的潜在触发因素。TCRanno 的注释能够区分健康和癌症(包括黑色素瘤、肺癌和乳腺癌)的 TCR 库。TCRanno 还通过分离具有特定特异性的 T 细胞,展示了在单细胞 TCRseq+基因表达数据分析中的有用性。

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