Novel Allele Detection Tool Benchmark and Application With Antibody Repertoire Sequencing Dataset

Xiujia Yang, Yan Zhu, Sen Chen, Huikun Zeng, Junjie Guan, Qilong Wang, Chunhong Lan, Deqiang Sun, Xueqing Yu, Zhenhai Zhang
2021 Frontiers in Immunology  
Detailed knowledge of the diverse immunoglobulin germline genes is critical for the study of humoral immunity. Hundreds of alleles have been discovered by analyzing antibody repertoire sequencing (Rep-seq or Ig-seq) data via multiple novel allele detection tools (NADTs). However, the performance of these NADTs through antibody sequences with intrinsic somatic hypermutations (SHMs) is unclear. Here, we developed a tool to simulate repertoires by integrating the full spectrum features of an
more » ... dy repertoire such as germline gene usage, junctional modification, position-specific SHM and clonal expansion based on 2152 high-quality datasets. We then systematically evaluated these NADTs using both simulated and genuine Ig-seq datasets. Finally, we applied these NADTs to 687 Ig-seq datasets and identified 43 novel allele candidates (NACs) using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the NACs detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.
doi:10.3389/fimmu.2021.739179 pmid:34764956 pmcid:PMC8576399 fatcat:2eahjibowrf7bimxld7p7nfzce