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TIRTL-seq:深度,定量和负担得起的配对TCR曲目序列排序

Mikhail V Pogorelyy¹, Allison M Kirk², Samir Adhikari²

¹St. Jude Children's Research Hospital, Memphis, TN, USA. mikhail.pogorelyy@stjude.org.

|November 25, 2025

概括

我们开发了吞吐量密集的快速TCR库测序 (TIRTL-seq) 以实现经济高效的对T细胞受体测序. 这种方法可以进行大规模研究,准确配对TCR链,并估计从单细胞到数百万个细胞的克隆频率.

科学领域:

免疫学免疫学免疫学
基因组学就是基因组学.
生物信息学是一种生物信息学.

背景情况:

T细胞受体 (TCR) 的α和β链序列决定了T细胞的特异性.
批量TCR测序具有成本效益,但缺乏链条配对数据.
单细胞TCR测序提供配对数据,但成本昂贵,吞吐量低.

研究的目的:

引入吞吐量密集的快速TCR库序列化 (TIRTL-seq),这是一种用于配对TCR目录序列化的新方法.
为了实现具有成本效益的,队列规模配对的TCR测序.
将批量和单细胞TCR测序的优势结合起来.

主要方法:

TIRTL-seq利用384个井板中的数百个TCR库的并行生成.
这种方法的成本不到每盘200美元.
它整合了对联TCR目录测序的实验和计算方法.

主要成果:

TIRTL-seq与大量的TCR-seq和10x Genomics Chromium技术进行了基准测试.
该研究确定了严重急性呼吸系统综合征冠状病毒2和爱斯坦-巴尔病毒特定的克隆扩张.
在纵向样本中观察到不同的克隆扩张动态.

结论:

TIRTL-seq提供了一种可从单细胞扩展到数百万T细胞的通用协议.
该方法提供了精确的克隆频率估计和准确的TCR链配对.
TIRTL-seq克服了现有的TCR测序方法的局限性,使得全面的曲目分析成为可能.

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