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从单细胞测序数据推断B细胞克隆系谱树的同型认知推断

Leah L Weber¹, Derek Reiman², Mrinmoy S Roddur¹

¹Department of Computer Science, University of Illinois at Urbana-Champaign, Urbana, IL 61801, USA.

|August 29, 2024

概括

我们开发了TRIBAL,这是一个新的算法,用于从单细胞RNA测序数据中重建B细胞克隆系的进化. 特里巴尔精确地模拟了体质突变和类交换重组,改善了各种应用的B细胞谱系追踪.

科学领域:

免疫学免疫学免疫学
计算生物学计算生物学
基因组学就是基因组学.

背景情况:

单细胞RNA测序 (scRNA-seq) 提供了关于在适应性免疫反应期间B细胞微演变的见解.
现有的遗传学方法主要集中在体质突变 (SHM),忽视了B细胞进化中的类开关重组 (CSR).
准确的B细胞进化史重建对于了解免疫反应和疾病至关重要.

研究的目的:

介绍TRIBAL (B细胞克隆系的树推断),用于重建B细胞进化史的算法.
从scRNA-seq数据中考虑SHM和CSR的B细胞系的最佳重建.
改进B细胞谱系追踪,用于诸如疫苗反应建模和治疗性抗体识别等应用.

主要方法:

开发TRIBAL算法用于B细胞克隆系的遗传学重建.
使用scRNA-seq数据来捕获SHM和CSR过程.
与现有方法进行比较分析,使用模拟和现实世界数据集.

主要成果:

与模拟中的现有方法相比,TRIBAL产生了更全面,更准确的B细胞系谱树.
通过使用真实世界的数据,TRIBAL成功地在亲和力成熟模型中重新总结了生物趋势.
与最先进的方法相比,重建的进化历史表现出更为节的阶级切换.

结论:

通过整合SHM和CSR,TRIBAL显著增强了B细胞谱系的追踪.
该算法为研究适应性免疫,疫苗反应和疾病进展提供了有价值的工具.
通过阐明B细胞进化,TRIBAL有助于识别潜在的治疗抗体.

关键词:

在B细胞谱系树上.在BCR中,BCR是指BCR.类开关重组组合类开关重组免疫基因组学免疫基因组学一个单细胞的RNA-seqq.身体上的超突变.

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