Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity.
Production of individualized V gene databases reveals high levels of immunoglobulin genetic diversity.
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个体化 V 基因数据库的产生揭示了高水平的免疫球蛋白遗传多样性。
DOI：
10.1038/ncomms13642
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发表时间：
2016-12-20
影响因子：
16.6
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中科院分区：
文献类型：
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要增进我们对 B 细胞生物学的理解，需要全面了解免疫球蛋白遗传学。仅针对人类和小鼠的经过验证的免疫球蛋白变量 (V) 基因数据库已接近完成。我们提出了一种新颖的计算方法 IgDiscover，它可以从表达的库中识别种系 V 基因，特异性为 100%。 IgDiscover 使用簇识别过程来生成候选序列，这些序列经过过滤后，将生成个体化的种系 V 基因数据库。 IgDiscover 在多个物种中进行了测试，通过基因组克隆和跨文库比较进行了验证，即使在可用的基因组序列有限的情况下，也可以生成全面的基因数据库。 IgDiscover 对印度和中国恒河猴等位基因含量的分析表明该物种具有高水平的免疫球蛋白基因多样性。此外，我们描述了一种新的人类 IGHV3-21 等位基因，并确认了 Balb/c 和 C57BL6 小鼠品系之间的显着基因差异，证明了 IgDiscover 作为种系 V 基因发现工具的强大功能。 当前抗体库 V 基因数据库存在局限性。这里 Corcoran 等人。开发一种名为 IgDiscover 的计算方法，可以从表达的抗体库中识别种系 V 基因序列，具有高特异性和完整性。
Comprehensive knowledge of immunoglobulin genetics is required to advance our understanding of B cell biology. Validated immunoglobulin variable (V) gene databases are close to completion only for human and mouse. We present a novel computational approach, IgDiscover, that identifies germline V genes from expressed repertoires to a specificity of 100%. IgDiscover uses a cluster identification process to produce candidate sequences that, once filtered, results in individualized germline V gene databases. IgDiscover was tested in multiple species, validated by genomic cloning and cross library comparisons and produces comprehensive gene databases even where limited genomic sequence is available. IgDiscover analysis of the allelic content of the Indian and Chinese-origin rhesus macaques reveals high levels of immunoglobulin gene diversity in this species. Further, we describe a novel human IGHV3-21 allele and confirm significant gene differences between Balb/c and C57BL6 mouse strains, demonstrating the power of IgDiscover as a germline V gene discovery tool. Current databases of V genes for antibody repertoire have limitations. Here Corcoran et al. develop a computational approach named IgDiscover that can identify germline V gene sequences from expressed antibody repertoires to high specificity and completeness.