The variable domains of antibodies and T-cell receptors (TCR) contain these proteins’ major binding regions. Alignment of these variable sequences to a numbering scheme allows equivalent residue positions to be annotated and for different molecules to be compared. Performing numbering is fundamental for immunoinformatics analysis and rational engineering of therapeutic molecules ([Shirai, 2014](javascript:;)). 抗体和 T 细胞受体 (TCR) 的可变域包含这些蛋白质的主要结合区域。这些可变序列与编号方案的比对允许注释等效的残基位置并比较不同的分子。进行编号是免疫信息学分析和治疗分子合理工程的基础(Shirai,2014)。
Several numbering schemes have been proposed, each is favoured by scientists in different immunological disciplines. The Kabat scheme ([Kabat et al., 1991](javascript:;)) was developed based on the location of regions of high sequence variation between sequences of the same domain type. It numbers antibody heavy (VH) and light (Vλ and Vκ) variable domains differently. Chothia’s scheme ([Al-Lazikani, 1997](javascript:;)) is the same as Kabat’s but corrects where an insertion is annotated around the first VH complementarity determining region (CDR) so that it corresponds to a structural loop. Similarly, the Enhanced Chothia scheme ([Abhinandan and Martin, 2008](javascript:;)) makes further structural corrections of indel positions. 已经提出了几种编号方案,每种方案都受到不同免疫学学科的科学家的青睐。 Kabat 方案(Kabat 等人,1991)是根据相同结构域类型的序列之间的高序列变异区域的位置而开发的。它对抗体重 (VH) 和轻 (Vλ 和 Vκ) 可变域进行不同编号。 Chothia 的方案(Al-Lazikani,1997)与 Kabat 的方案相同,但纠正了第一个 VH 互补决定区 (CDR) 周围注释的插入位置,使其对应于结构环。类似地,增强型 Chothia 方案(Abhinandan 和 Martin,2008)对 indel 位置进行了进一步的结构修正。
In contrast to these Kabat-like schemes, IMGT ([Lefranc, 2003](javascript:;)) and AHo ([Honegger and Plückthun, 2001](javascript:;)) both define unique schemes for antibody and T cell receptor (TCR) (Vα and Vβ) variable domains. Thus, equivalent residue positions can easily be compared between domain types. IMGT and AHo differ in the number of positions they annotate (128 and 149 respectively) and where they consider indels to occur. 与这些类似 Kabat 的方案相比,IMGT (Lefranc, 2003) 和 AHo (Honegger 和 Plückthun, 2001) 都定义了抗体和 T 细胞受体 (TCR)(Vα 和 Vβ)可变域的独特方案。因此,可以轻松比较结构域类型之间的等效残基位置。 IMGT 和 AHo 的不同之处在于它们注释的位置数量(分别为 128 和 149)以及它们认为发生插入缺失的位置。
Separate online interfaces exist that can apply each numbering scheme: Kabat, Chothia and Enhanced Chothia through Abnum ([Abhinandan and Martin, 2008](javascript:;)); IMGT through DomainGapAlign ([Ehrenmann, 2010](javascript:;)); and AHo through PyIgClassify ([Adolf-Bryfogle et al., 2015](javascript:;)). No program currently exists that can apply all schemes or for which an executable is available under open license. 存在可以应用每种编号方案的单独在线界面:Kabat、Chothia 和通过 Abnum 增强的 Chothia(Abhinandan 和 Martin,2008); IMGT 通过 DomainGapAlign(Ehrenmann,2010);和 AHo 通过 PyIgClassify(Adolf-Bryfogle 等人,2015)。当前不存在可以应用所有方案或在开放许可下可用的可执行文件的程序。
We have developed ANARCI, a program that can annotate sequences with all five of the numbering schemes described above. We provide both a web-interface and the software under open license so that these fundamental annotations can be easily available for further immunoinformatics analyses. 我们开发了 ANARCI,这是一个可以使用上述所有五种编号方案来注释序列的程序。提供网络界面和开放许可下的软件,以便这些基本注释可以轻松用于进一步的免疫信息学分析。
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