Aouinti Safa, Malouche Dhafer, Giudicelli Véronique, Kossida Sofia, Lefranc Marie-Paule
IMGT, the international ImMunoGeneTics information system, Laboratoire d'ImmunoGénétique Moléculaire LIGM, Institut de Génétique Humaine IGH, UPR CNRS 1142, Montpellier University, Montpellier cedex 5, France.
Higher School of Statistics and Information Analysis, University of Carthage, Tunis, Tunisia.
PLoS One. 2015 Nov 5;10(11):e0142353. doi: 10.1371/journal.pone.0142353. eCollection 2015.
The adaptive immune responses of humans and of other jawed vertebrate species (gnasthostomata) are characterized by the B and T cells and their specific antigen receptors, the immunoglobulins (IG) or antibodies and the T cell receptors (TR) (up to 2.1012 different IG and TR per individual). IMGT, the international ImMunoGeneTics information system (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc (Montpellier University and CNRS) to manage the huge and complex diversity of these antigen receptors. IMGT built on IMGT-ONTOLOGY concepts of identification (keywords), description (labels), classification (gene and allele nomenclature) and numerotation (IMGT unique numbering), is at the origin of immunoinformatics, a science at the interface between immunogenetics and bioinformatics. IMGT/HighV-QUEST, the first web portal, and so far the only one, for the next generation sequencing (NGS) analysis of IG and TR, is the paradigm for immune repertoire standardized outputs and immunoprofiles of the adaptive immune responses. It provides the identification of the variable (V), diversity (D) and joining (J) genes and alleles, analysis of the V-(D)-J junction and complementarity determining region 3 (CDR3) and the characterization of the 'IMGT clonotype (AA)' (AA for amino acid) diversity and expression. IMGT/HighV-QUEST compares outputs of different batches, up to one million nucleotide sequencesfor the statistical module. These high throughput IG and TR repertoire immunoprofiles are of prime importance in vaccination, cancer, infectious diseases, autoimmunity and lymphoproliferative disorders, however their comparative statistical analysis still remains a challenge. We present a standardized statistical procedure to analyze IMGT/HighV-QUEST outputs for the evaluation of the significance of the IMGT clonotype (AA) diversity differences in proportions, per gene of a given group, between NGS IG and TR repertoire immunoprofiles. The procedure is generic and suitable for evaluating significance of the IMGT clonotype (AA) diversity and expression per gene, and for any IG and TR immunoprofiles of any species.
人类和其他有颌脊椎动物（gnasthostomata）的适应性免疫反应以B细胞和T细胞及其特异性抗原受体、免疫球蛋白（IG）或抗体以及T细胞受体（TR）为特征（每个人多达2.1×10¹²种不同的IG和TR）。国际免疫基因信息系统IMGT（http://www.imgt.org）由玛丽 - 保罗·勒弗朗（蒙彼利埃大学和法国国家科学研究中心）于1989年创建，用于管理这些抗原受体的巨大而复杂的多样性。IMGT建立在IMGT本体论的识别（关键词）、描述（标签）、分类（基因和等位基因命名法）和编号（IMGT唯一编号）概念之上，是免疫信息学的起源，免疫信息学是一门处于免疫遗传学和生物信息学交叉领域的科学。IMGT/HighV-QUEST是第一个也是迄今为止唯一用于IG和TR的下一代测序（NGS）分析的门户网站，是适应性免疫反应的免疫库标准化输出和免疫图谱的范例。它提供可变（V）、多样（D）和连接（J）基因及等位基因的识别，V-（D）-J连接和互补决定区3（CDR3）的分析，以及“IMGT克隆型（AA）”（AA代表氨基酸）多样性和表达的表征。IMGT/HighV-QUEST可比较不同批次的输出结果，统计模块最多可处理100万个核苷酸序列。这些高通量的IG和TR免疫库免疫图谱在疫苗接种、癌症、传染病、自身免疫性疾病和淋巴增殖性疾病中至关重要，然而它们的比较统计分析仍然是一个挑战。我们提出了一种标准化的统计程序，用于分析IMGT/HighV-QUEST的输出结果，以评估在NGS的IG和TR免疫库免疫图谱中，给定组中每个基因的IMGT克隆型（AA）多样性比例差异的显著性。该程序具有通用性，适用于评估每个基因的IMGT克隆型（AA）多样性和表达的显著性，以及任何物种的任何IG和TR免疫图谱。
