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用于定义和追踪人类实体器官及造血干细胞移植后同种反应性T细胞克隆的综合分析工具集

Integrated Analysis Toolset for Defining and Tracking Alloreactive T-cell Clones After Human Solid Organ and Hematopoietic Stem Cell Transplantation.

作者信息

Obradovic Aleksandar, Shen Yufeng, Sykes Megan, Fu Jianing

机构信息

Columbia Center for Translational Immunology, Department of Medicine; Columbia University, New York, NY 10032, United States.

Department of Systems Biology; Columbia University, New York, NY 10032, United States.

出版信息

Softw Impacts. 2021 Nov;10. doi: 10.1016/j.simpa.2021.100142. Epub 2021 Sep 23.

DOI:10.1016/j.simpa.2021.100142
PMID:35291378
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8920412/
Abstract

We have developed a suite of tools for integrated analysis of T-Cell-Receptor Sequencing data to define and track alloreactive T-cells in human transplant studies. This has enabled discovery of sequences and patterns of T-cell enrichment and deletion associated with clinical outcomes such as transplant rejection and tolerance. The codebase includes user-friendly default analyses with customizable parameters which greatly accelerate computational workflows and provide robust statistics comparing post-transplant specimens to pre-transplant baseline. It also includes helper functions for robust characterization of T-cell-repertoire diversity, sample-to-sample divergence, resolution of sample-of-origin ambiguity in pooled assays, and functions to output all sequences defined as alloreactive.

摘要

我们开发了一套用于T细胞受体测序数据综合分析的工具,以在人类移植研究中定义和追踪同种异体反应性T细胞。这使得能够发现与移植排斥和耐受等临床结果相关的T细胞富集和缺失的序列及模式。该代码库包括具有可定制参数的用户友好型默认分析,极大地加速了计算工作流程,并提供了将移植后标本与移植前基线进行比较的可靠统计数据。它还包括用于T细胞库多样性的稳健表征、样本间差异、混合检测中起源样本模糊性的解析以及输出所有定义为同种异体反应性序列的辅助函数。

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Immune cell profiling in intestinal transplantation.肠移植中的免疫细胞分析。
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本文引用的文献

1
Lymphohematopoietic graft-versus-host responses promote mixed chimerism in patients receiving intestinal transplantation.淋巴细胞造血移植物抗宿主反应促进接受肠道移植患者的混合嵌合体形成。
J Clin Invest. 2021 Apr 15;131(8). doi: 10.1172/JCI141698.
2
CD8+ T-Cell Repertoire in Human Leukocyte Antigen Class I-Mismatched Alloreactive Immune Response.CD8+ T 细胞库在人类白细胞抗原 I 类错配同种反应性免疫应答中的作用。
Front Immunol. 2021 Jan 20;11:588741. doi: 10.3389/fimmu.2020.588741. eCollection 2020.
3
T cell repertoire analysis suggests a prominent bystander response in human cardiac allograft vasculopathy.T 细胞库分析提示在人类心脏移植血管病中存在显著的旁观者反应。
Am J Transplant. 2021 Apr;21(4):1465-1476. doi: 10.1111/ajt.16333. Epub 2020 Oct 26.
4
Analysis of the Whole CDR3 T Cell Receptor Repertoire after Hematopoietic Stem Cell Transplantation in 2 Clinical Cohorts.两个临床队列中造血干细胞移植后全CDR3 T细胞受体库分析
Biol Blood Marrow Transplant. 2020 Jun;26(6):1050-1070. doi: 10.1016/j.bbmt.2020.01.020. Epub 2020 Feb 18.
5
Deletion of donor-reactive T cell clones after human liver transplant.肝移植后供者反应性 T 细胞克隆的缺失。
Am J Transplant. 2020 Feb;20(2):538-545. doi: 10.1111/ajt.15592. Epub 2019 Oct 3.
6
Next generation sequencing based assessment of the alloreactive T cell receptor repertoire in kidney transplant patients during rejection: a prospective cohort study.基于下一代测序的肾移植受者排斥反应期间同种反应性 T 细胞受体库评估:一项前瞻性队列研究。
BMC Nephrol. 2019 Sep 2;20(1):346. doi: 10.1186/s12882-019-1541-5.
7
Human Intestinal Allografts Contain Functional Hematopoietic Stem and Progenitor Cells that Are Maintained by a Circulating Pool.人类肠道同种异体移植物中含有功能性造血干细胞和祖细胞,这些细胞由循环池维持。
Cell Stem Cell. 2019 Feb 7;24(2):227-239.e8. doi: 10.1016/j.stem.2018.11.007. Epub 2018 Nov 29.
8
Quantifying size and diversity of the human T cell alloresponse.量化人类 T 细胞同种异体反应的大小和多样性。
JCI Insight. 2018 Aug 9;3(15). doi: 10.1172/jci.insight.121256.
9
Bidirectional intragraft alloreactivity drives the repopulation of human intestinal allografts and correlates with clinical outcome.双向移植物内同种异体反应性驱动人肠道同种异体移植物的再填充,并与临床结果相关。
Sci Immunol. 2016 Oct;1(4). doi: 10.1126/sciimmunol.aah3732. Epub 2016 Oct 7.
10
Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients.追踪供体反应性T细胞:耐受肾移植患者中克隆清除的证据。
Sci Transl Med. 2015 Jan 28;7(272):272ra10. doi: 10.1126/scitranslmed.3010760.