Qing Wang, Yuzhou Feng, Yanfei Wang, Bo Li, Jianguo Wen, Xiaobo Zhou, Qianqian Song
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引用次数: 0
Abstract
Antibodies play a pivotal role in immune defense and serve as key therapeutic agents. The process of affinity maturation, wherein antibodies evolve through somatic mutations to achieve heightened specificity and affinity to target antigens, is crucial for effective immune response. Despite their significance, assessing antibody-antigen binding affinity remains challenging due to limitations in conventional wet lab techniques. To address this, we introduce AntiFormer, a graph-based large language model designed to predict antibody binding affinity. AntiFormer incorporates sequence information into a graph-based framework, allowing for precise prediction of binding affinity. Through extensive evaluations, AntiFormer demonstrates superior performance compared with existing methods, offering accurate predictions with reduced computational time. Application of AntiFormer to severe acute respiratory syndrome coronavirus 2 patient samples reveals antibodies with strong neutralizing capabilities, providing insights for therapeutic development and vaccination strategies. Furthermore, analysis of individual samples following influenza vaccination elucidates differences in antibody response between young and older adults. AntiFormer identifies specific clonotypes with enhanced binding affinity post-vaccination, particularly in young individuals, suggesting age-related variations in immune response dynamics. Moreover, our findings underscore the importance of large clonotype category in driving affinity maturation and immune modulation. Overall, AntiFormer is a promising approach to accelerate antibody-based diagnostics and therapeutics, bridging the gap between traditional methods and complex antibody maturation processes.
期刊介绍:
Briefings in Bioinformatics is an international journal serving as a platform for researchers and educators in the life sciences. It also appeals to mathematicians, statisticians, and computer scientists applying their expertise to biological challenges. The journal focuses on reviews tailored for users of databases and analytical tools in contemporary genetics, molecular and systems biology. It stands out by offering practical assistance and guidance to non-specialists in computerized methodologies. Covering a wide range from introductory concepts to specific protocols and analyses, the papers address bacterial, plant, fungal, animal, and human data.
The journal's detailed subject areas include genetic studies of phenotypes and genotypes, mapping, DNA sequencing, expression profiling, gene expression studies, microarrays, alignment methods, protein profiles and HMMs, lipids, metabolic and signaling pathways, structure determination and function prediction, phylogenetic studies, and education and training.