TRIBAL: Tree Inference of B cell Clonal Lineages.
TRIBAL: Tree Inference of B cell Clonal Lineages.
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TRIBAL：B 细胞克隆谱系的树推断。
DOI：
10.1101/2023.11.27.568874
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Khan,AlyA
中科院分区：
文献类型：
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作者：
Weber,LeahL;Reiman,Derek;Roddur,MrinmoyS;Qi,Yuanyuan;El-Kebir,Mohammed;Khan,AlyA
B细胞是适应性免疫系统的重要组成部分。单细胞RNA测序（scRNA-seq）允许分析B细胞受体（BCR）序列和基因表达。然而，理解B细胞响应特定刺激的适应性和进化机制仍然是免疫学领域的重大挑战。我们介绍了一种新的方法，TRIBAL，其目的是从scRNA-seq数据推断克隆相关B细胞的进化历史。TRIBAL的主要观点是，将同种型数据纳入B细胞谱系推断问题对于减少仅考虑受体序列时出现的系统发育不确定性是有价值的。因此，TRIBAL推断的B细胞谱系树共同捕获在亲和力成熟期间引入到B细胞受体的体细胞突变和在类别转换重组期间的同种型转变。此外，TRIBALinfers同种型转移概率，这是有价值的深入了解类切换的动态。通过计算机模拟实验，我们证明了TRIBAL推断同种型转换概率的能力，以区分直接与顺序转换的B细胞群体。与竞争方法相比，这导致更准确的B细胞谱系树和相应的祖先序列和类别转换重建。使用真实世界的scRNA-seq数据集，我们证明了TRIBAL在模型亲和力成熟系统中重现了预期的生物学趋势。此外，由TRIBAL推断的B细胞谱系树对于BCR序列与通过竞争方法推断的那些同样合理，但是对于测序的B细胞的同种型产生较低的熵分区。因此，我们的方法有可能进一步促进我们对疫苗反应，疾病进展和治疗性抗体鉴定的理解。
B cells are a critical component of the adaptive immune system. Single cell RNA-sequencing (scRNA-seq) has allowed for both profiling of B cell receptor (BCR) sequences and gene expression. However, understanding the adaptive and evolutionary mechanisms of B cells in response to specific stimuli remains a significant challenge in the field of immunology. We introduce a new method, TRIBAL, which aims to infer the evolutionary history of clonally related B cells from scRNA-seq data. The key insight ofTRIBALis that inclusion of isotype data into the B cell lineage inference problem is valuable for reducing phylogenetic uncertainty that arises when only considering the receptor sequences. Consequently, theTRIBALinferred B cell lineage trees jointly capture the somatic mutations introduced to the B cell receptor during affinity maturation and isotype transitions during class switch recombination. In addition,TRIBALinfers isotype transition probabilities that are valuable for gaining insight into the dynamics of class switching. Viain silicoexperiments, we demonstrate thatTRIBALinfers isotype transition probabilities with the ability to distinguish between direct versus sequential switching in a B cell population. This results in more accurate B cell lineage trees and corresponding ancestral sequence and class switch reconstruction compared to competing methods. Using real-world scRNA-seq datasets, we show thatTRIBALrecapitulates expected biological trends in a model affinity maturation system. Furthermore, the B cell lineage trees inferred byTRIBALwere equally plausible for the BCR sequences as those inferred by competing methods but yielded lower entropic partitions for the isotypes of the sequenced B cell. Thus, our method holds the potential to further advance our understanding of vaccine responses, disease progression, and the identification of therapeutic antibodies.