Department of Biosystems Science and Engineering, ETH Zürich, 4058 Basel, Switzerland.
Institute of Microbiology.
Bioinformatics. 2017 Dec 15;33(24):3938-3946. doi: 10.1093/bioinformatics/btx533.
The evolution of antibody repertoires represents a hallmark feature of adaptive B-cell immunity. Recent advancements in high-throughput sequencing have dramatically increased the resolution to which we can measure the molecular diversity of antibody repertoires, thereby offering for the first time the possibility to capture the antigen-driven evolution of B cells. However, there does not exist a repertoire simulation framework yet that enables the comparison of commonly utilized phylogenetic methods with regard to their accuracy in inferring antibody evolution.
Here, we developed AbSim, a time-resolved antibody repertoire simulation framework, which we exploited for testing the accuracy of methods for the phylogenetic reconstruction of B-cell lineages and antibody molecular evolution. AbSim enables the (i) simulation of intermediate stages of antibody sequence evolution and (ii) the modeling of immunologically relevant parameters such as duration of repertoire evolution, and the method and frequency of mutations. First, we validated that our repertoire simulation framework recreates replicates topological similarities observed in experimental sequencing data. Second, we leveraged Absim to show that current methods fail to a certain extent to predict the true phylogenetic tree correctly. Finally, we formulated simulation-validated guidelines for antibody evolution, which in the future will enable the development of accurate phylogenetic methods.
https://cran.r-project.org/web/packages/AbSim/index.html.
Supplementary data are available at Bioinformatics online.
抗体库的进化代表了适应性 B 细胞免疫的一个显著特征。高通量测序的最新进展极大地提高了我们测量抗体库分子多样性的分辨率，从而首次有可能捕捉到 B 细胞的抗原驱动进化。然而，目前还没有一个能够模拟抗体库的框架，可以比较常用的系统发生方法在推断抗体进化方面的准确性。
在这里，我们开发了 AbSim，一个时间分辨的抗体库模拟框架，我们利用它来测试用于 B 细胞谱系和抗体分子进化的系统发生重建的方法的准确性。AbSim 能够模拟抗体序列进化的中间阶段，并且可以对免疫相关参数进行建模，例如抗体库进化的持续时间、突变的方法和频率。首先，我们验证了我们的库模拟框架再现了实验测序数据中观察到的重复拓扑相似性。其次，我们利用 Absim 表明，目前的方法在一定程度上无法正确预测真实的系统发生树。最后，我们制定了经过模拟验证的抗体进化指南，这将有助于未来开发准确的系统发生方法。
https://cran.r-project.org/web/packages/AbSim/index.html。
补充数据可在《生物信息学》在线获取。
