下一代测序和蛋白质质谱分析全面分析人类细胞和血清抗体库。
Next-generation sequencing and protein mass spectrometry for the comprehensive analysis of human cellular and serum antibody repertoires.
机构信息
Department of Chemical Engineering, University of Texas at Austin, Austin, TX 78712-1062, USA; Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712-1062, USA.
Center for Systems & Synthetic Biology, University of Texas at Austin, Austin, TX 78712-1062, USA; Department of Biomedical Engineering, University of Texas at Austin, Austin, TX 78712-1062, USA.
出版信息
Curr Opin Chem Biol. 2015 Feb;24:112-20. doi: 10.1016/j.cbpa.2014.11.007. Epub 2014 Nov 25.
Recent developments of high-throughput technologies are enabling the molecular-level analysis and bioinformatic mining of antibody-mediated (humoral) immunity in humans at an unprecedented level. These approaches explore either the sequence space of B-cell receptor repertoires using next-generation deep sequencing (BCR-seq), or the amino acid identities of antibody in blood using protein mass spectrometry (Ig-seq), or both. Generalizable principles about the molecular composition of the protective humoral immune response are being defined, and as such, the field could supersede traditional methods for the development of diagnostics, vaccines, and antibody therapeutics. Three key challenges remain and have driven recent advances: (1) incorporation of innovative techniques for paired BCR-seq to ascertain the complete antibody variable-domain VH:VL clonotype, (2) integration of proteomic Ig-seq with BCR-seq to reveal how the serum antibody repertoire compares with the antibody repertoire encoded by circulating B cells, and (3) a demand to link antibody sequence data to functional meaning (binding and protection).
高通量技术的最新发展使得人们能够以前所未有的水平在分子水平上分析和挖掘人类抗体介导的（体液）免疫的生物信息。这些方法要么使用下一代深度测序（BCR-seq）探索 B 细胞受体库的序列空间，要么使用蛋白质质谱（Ig-seq）探索血液中抗体的氨基酸同一性，或者两者兼而有之。关于保护性体液免疫反应的分子组成的普遍原则正在被定义，因此，该领域可能会取代传统的诊断、疫苗和抗体治疗药物的开发方法。仍有三个关键挑战，并且推动了最近的进展：（1）结合创新的配对 BCR-seq 技术，以确定完整的抗体可变区 VH:VL 克隆型，（2）将蛋白质组学 Ig-seq 与 BCR-seq 整合，以揭示血清抗体库与循环 B 细胞编码的抗体库的比较，以及（3）需要将抗体序列数据与功能意义（结合和保护）联系起来。
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