Using antibody next generation sequencing to aid antibody engineering

“抗体是由有颌脊椎动物的免疫系统产生的蛋白质，它识别并消除生物体中的致病分子。它们的结合可塑性是由于它们的巨大多样性而产生的。估计的总独特人抗体库多样性在1011的范围内。下一代测序技术（NGS）的出现使我们有可能对这种多样性进行快照。在这里，我们描述了我们使用UCB Pharma提供的大型NGS数据集的工作，该数据集包含来自约500个个体的13.5m重链和轻链。通过研究这个数据集，我们的目标是建立一组描述符，使我们能够正式询问物种内和跨物种免疫库的属性。此外，UCB Pharma拥有涵盖多个物种的全面NGS数据集，包括人类、小鼠、美洲驼和兔。深入了解种间抗体个体发生将突出共性和差异。这样的洞察力可以导致什么是“人”抗体的定义，并更好地理解抗体成熟的机制。对抗体库的彻底分析可以揭示免疫系统的成熟，为改进疫苗设计和药物发现铺平道路。将免疫对象的NGS数据集映射到抗体结构空间将询问抗体个体发育过程的级联并有助于创建抗体成熟模型。BBSRC优先事项：健康生物科学，数据驱动生物学，工业生物技术的新治疗方法，生物科学的系统方法“BfH，WCUB，ENWW

"Antibodies are proteins produced by immune systems of jawed vertebrates that recognize and eliminate pathogenic molecules from the organism. Their binding malleability arises as a result of their great diversity. The estimated total unique human antibody repertoire diversity lies in the range of 1011. The advent of Next Generation Sequencing (NGS) has made it possible to produce snapshots of this diversity. Here we describe our work with a large NGS dataset provided by UCB Pharma comprising 13.5m heavy and light chains from ~500 individuals. By studying this dataset we aim to establish a set of descriptors that will allow us to formally interrogate the properties of within and across species immune repertoires. Furthermore, UCB Pharma have comprehensive NGS datasets across a number of species, including human, mouse, llama and rabbit. Deeper understanding of inter-species antibody ontogeny would highlight commonalities and differences. Such insight can lead to a definition of what construes a 'human' antibody and better understanding of the mechanics of antibody maturation. Thorough analysis of antibody repertoires can shed light on immune system maturation paving the way for improved vaccine design and drug discovery. Mapping of NGS datasets of immunized subjects to the antibody structure space will interrogate cascades of the antibody ontogeny process and aid to create an antibody maturation model.BBSRC priorities: Bioscience for Health, Data driven biology, New therapeutic approaches to industrial biotechnology, Systems approaches to the bioscienc"BfH, WCUB, ENWW