New methods and software tools for high throughput CDR3 spectratyping. Application to T lymphocyte repertoire modifications during experimental malaria

New methods and software tools for high throughput CDR3 spectratyping. Application to T lymphocyte repertoire modifications during experimental malaria
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DOI:
10.1016/s0022-1759(03)00225-4
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发表时间:
2003-07-01
影响因子:
2.2
通讯作者:
Six, A
Six, A
中科院分区:
医学4区
文献类型:
--
作者:
Collette, A;Cazenave, PA;Six, A

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T 或 B 细胞的免疫组库经常通过互补决定区 3 (CDR3) 谱型进行研究。然而。用这种方法获得的数据通常会受到有偏见的眼睛分析。我们最近开发了 ISEApeaks 软件包,用于检索和处理来自自动测序仪的峰数据,从中获得 CDR3 谱类型数据。我们描述了基于两个新的特定模块和多元统计的 CDR3 谱类型分析的一般策略。第一个模块解决了峰值平滑的关键问题。第二个是用于分析 CDR3 谱类型的工具箱。其中包括扰动计算、循环峰值查找、扩展评估和数据挖掘。为了说明我们的方法,我们评估了伯氏疟原虫 ANKA (PbA) 感染引起的复杂 TCRB 库修饰。这种全面且详尽的库分析方法引起了 T 淋巴细胞库和 B 淋巴细胞库研究的普遍兴趣,目前已用于各种病理学和临床试验的人类队列中。 (C) 2003 Elsevier B.V. 保留所有权利。
Immune repertoires of T or B cells are very often studied by Complementary Determining Region 3 (CDR3) spectratyping. However. data obtained with this method is usually subject to a biased eye analysis. We developed recently the ISEApeaks software package to retrieve and handle peak data from automated sequencers, from which CDR3 spectratype data is obtained. We describe a general strategy for CDR3 spectratype analysis based on two new specific modules and multivariate statistics. The first module addresses the crucial problem of peak smoothing. The second is a toolbox for the analysis of CDR3 spectratypes. which includes perturbation computation, recurrent peak finding, expansion assessment and datamining. To illustrate our approach, we assessed the complex TCRB repertoire modifications induced by Plasmodium berghei ANKA (PbA) infection. This global and exhaustive repertoire analysis approach is of general interest for T- and B-lymphocyte repertoire studies and is currently used in human cohorts in various pathologies and during clinical trials. (C) 2003 Elsevier B.V. All rights reserved.