hAb-Convergent: an antibody rearrangement analysis system for therapeutic antibody engineering based on convergent evolution.

Abstract

In therapeutic antibody engineering, utilizing naturally occurring mutations in the human body as a reference for modification is an emerging trend. The theory of convergent evolution presents a viable solution. Nevertheless, the nonuniformity of the antibody rearrangement analysis system and the difficulty in identifying the heavy-chain D-region are significant challenges to research and application. To address these limitations, we developed hAb (human antibody)-Convergent, a novel tool designed to assist users in quickly identifying candidate mutation hotspots of input antibody sequences in real human immune responses for subsequent antibody engineering. It uses antibody rearrangement features-based (V, D, J genes and CDR-H3 length) rather than traditional sequence-based strategies while ensuring the security of the original sequence. Combining more inclusive D-region identification and analysis methods, it can recognize and analyze the convergence of antibodies across various individuals. Additionally, given the limitations of obtaining antibody nucleotide sequences from academic literature, it provides an optimized approach for direct analysis and rapid comparison using amino acid sequences. hAb-Convergent bridges gaps in antibody engineering by linking natural evolution patterns to in vitro design, with implications for universal vaccine development. The tool can be freely accessed at https://nmdc.cn/zoe/.