论文标题

使用B细胞受体谱系结构预测亲和力

Using B cell receptor lineage structures to predict affinity

论文作者

Ralph, Duncan K., Matsen IV, Frederick A.

论文摘要

我们经常面对大量抗体,并希望选择对其同源抗原具有最高亲和力的抗体。例如,在为新病原体开发一线治疗时,我们可能会寻找已康复的患者中的这种抗体。存在实现这一目标的有效实验方法,例如细胞分类和诱饵。但是它们耗时且昂贵。 B细胞受体(BCR)曲目的下一代测序提供了序列的附加来源,如果我们有一种可靠的方法来选择最佳抗体编码的方法。在本文中,我们介绍了一种使用相关序列家族的进化信息的方法,该序列共享一个天真的祖先,以预测每种产生的抗体对其抗原的亲和力。当与抗原身份的信息结合使用时,该方法应提供有效的新抗体来源。我们还引入了一种相关任务的方法:考虑到感兴趣的抗体及其推断的祖先谱系,树上的分支可能会藏有关键的亲和力增强突变?这些方法是作为持续开发Partis BCR推理软件包的一部分实现的,可从https://github.com/psathyrella/partis获得。

We are frequently faced with a large collection of antibodies, and want to select those with highest affinity for their cognate antigen. When developing a first-line therapeutic for a novel pathogen, for instance, we might look for such antibodies in patients that have recovered. There exist effective experimental methods of accomplishing this, such as cell sorting and baiting; however they are time consuming and expensive. Next generation sequencing of B cell receptor (BCR) repertoires offers an additional source of sequences that could be tapped if we had a reliable method of selecting those coding for the best antibodies. In this paper we introduce a method that uses evolutionary information from the family of related sequences that share a naive ancestor to predict the affinity of each resulting antibody for its antigen. When combined with information on the identity of the antigen, this method should provide a source of effective new antibodies. We also introduce a method for a related task: given an antibody of interest and its inferred ancestral lineage, which branches in the tree are likely to harbor key affinity-increasing mutations? These methods are implemented as part of continuing development of the partis BCR inference package, available at https://github.com/psathyrella/partis.

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