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

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 antibody 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.

Knowledge-based antibody repertoire simulation, a novel allele detection tool evaluation and application

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 antibody 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 alleles using defined criteria. Twenty-five alleles were validated through findings of other sources. In addition to the novel alleles detected, our simulation tool, the results of our comparison, and the streamline of this process may benefit further humoral immunity studies via Ig-seq.

Prevalence of allelic and genotypic variants of the rs1143627 polymorphism in the IL1β gene among patients with typhoid

Objective. To evaluatethe role of allelic and genotypic variants of gene IL1β polymorphism rs1143627 in susceptibility to typhoid fever (TF). Materials and methods. 41 patients with TF and 84 chronic carriers of S. typhi were endrolled in the study. Control group included 91 healthy individuals, All of the individuals under study were Uzbeks. DNA samples were isolated from peripheric blood with the kit Ribo-sorb (AmpliSens®, Russia). Genotyping of polymorphism rs1143627 of gene IL1β was carried out by the standard PCR using kits “SNP-Express” (LLC NPF “LITECH”, Russia) according to the instruction of manufacturer. Results. The domination of allele 31T was found in the main group (patients and carriers). Its frequency was significantly lower in comparison with the control group (51.2% and 67.0%, respectively; χ2 = 10.8; p = 0.001). Minor allele -31С cytokine IL1β, on the contrary was detected more frequently in patients with TF (48.8%), than in the control group (33.0%) in χ2 = 10.8 and p = 0.001. Calculated relative chance of this allele detection in the main group in comparison with control group was OR = 1.9 in 95% CI 1.304-2.88. Conclusion. Genotypic variant C/C of polymorphism rs1143627 of the gene IL1β made a certain contribution into forming of generic structure of susceptibility to S. typhi. Risk of susceptibility of macro organism to pathogen in the presence of this genotype is higher more than 2.5 times (χ2 = 4.3; p = 0.04; CI 95% 1.037–7.359). Key words: Typhoid fever, bacteria carrier, bacteria S. typhi, polymorphism rs1143627 of the gene IL1β