Computational Biology Program, Fred Hutchinson Cancer Research Center, Seattle, WA, United States.
Front Immunol. 2018 Oct 31;9:2451. doi: 10.3389/fimmu.2018.02451. eCollection 2018.
B cell receptor sequences evolve during affinity maturation according to a Darwinian process of mutation and selection. Phylogenetic tools are used extensively to reconstruct ancestral sequences and phylogenetic trees from affinity-matured sequences. In addition to using general-purpose phylogenetic methods, researchers have developed new tools to accommodate the special features of B cell sequence evolution. However, the performance of classical phylogenetic techniques in the presence of B cell-specific features is not well understood, nor how much the newer generation of B cell specific tools represent an improvement over classical methods. In this paper we benchmark the performance of classical phylogenetic and new B cell-specific tools when applied to B cell receptor sequences simulated from a forward-time model of B cell receptor affinity maturation toward a mature receptor. We show that the currently used tools vary substantially in terms of tree structure and ancestral sequence inference accuracy. Furthermore, we show that there are still large performance gains to be achieved by modeling the special mutation process of B cell receptors. These conclusions are further strengthened with real data using the rules of isotype switching to count possible violations within each inferred phylogeny.
B 细胞受体序列在亲和力成熟过程中根据突变和选择的达尔文过程进化。系统发育工具被广泛用于从亲和力成熟序列重建祖先序列和系统发育树。除了使用通用的系统发育方法外，研究人员还开发了新的工具来适应 B 细胞序列进化的特殊特征。然而，经典系统发育技术在存在 B 细胞特异性特征时的性能尚不清楚，也不清楚新一代的 B 细胞特异性工具相对于经典方法有多大的改进。在本文中，我们对经典系统发育和新的 B 细胞特异性工具在应用于从 B 细胞受体亲和力成熟的正向时间模型模拟的 B 细胞受体序列时的性能进行了基准测试，这些序列朝着成熟受体进化。我们表明，目前使用的工具在树结构和祖先序列推断准确性方面存在很大差异。此外，我们还表明，通过对 B 细胞受体的特殊突变过程进行建模，仍然可以获得很大的性能提升。使用同种型转换规则对每个推断的系统发育树内的可能违反情况进行计数，使用真实数据进一步加强了这些结论。
