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Observed T 细胞受体空间数据库支持配对链库挖掘、一致性分析和语言建模。

The Observed T Cell Receptor Space database enables paired-chain repertoire mining, coherence analysis, and language modeling.

机构信息

Oxford Protein Informatics Group, Department of Statistics, University of Oxford, 24-29 St Giles', OX1 3LB Oxford, UK.

Oxford Protein Informatics Group, Department of Statistics, University of Oxford, 24-29 St Giles', OX1 3LB Oxford, UK.

出版信息

Cell Rep. 2024 Sep 24;43(9):114704. doi: 10.1016/j.celrep.2024.114704. Epub 2024 Aug 29.

Abstract

T cell activation is governed through T cell receptors (TCRs), heterodimers of two sequence-variable chains (often an α and β chain) that synergistically recognize antigen fragments presented on cell surfaces. Despite this, there only exist repositories dedicated to collecting single-chain, not paired-chain, TCR sequence data. We addressed this gap by creating the Observed TCR Space (OTS) database, a source of consistently processed and annotated, full-length, paired-chain TCR sequences. Currently, OTS contains 5.35 million redundant (1.63 million non-redundant), predominantly human sequences from across 50 studies and at least 75 individuals. Using OTS, we identify pairing biases, public TCRs, and distinct chain coherence patterns relative to antibodies. We also release a paired-chain TCR language model, providing paired embedding representations and a method for residue in-filling conditional on the partner chain. OTS will be updated as a central community resource and is freely downloadable and available as a web application.

摘要

T 细胞的激活受 T 细胞受体(TCRs)调控,TCRs 由两个序列可变链(通常是一个α链和一个β链)组成的异二聚体,协同识别细胞表面呈现的抗原片段。尽管如此,目前仅存在专门用于收集单链而不是配对链 TCR 序列数据的存储库。我们通过创建 Observed TCR Space(OTS)数据库来解决这一差距,OTS 是一个经过一致处理和注释的全长配对 TCR 序列的来源。目前,OTS 包含 535 万条冗余(163 万条非冗余)序列,主要来自 50 项研究和至少 75 个人。使用 OTS,我们确定了配对偏好、公共 TCR 以及与抗体相比的独特链一致性模式。我们还发布了一个配对 TCR 语言模型,提供了配对嵌入表示以及一种基于伙伴链的残基填充条件方法。OTS 将作为一个中央社区资源进行更新,并可免费下载,也可作为网络应用程序使用。

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