Ong Edison, Wong Mei U, He Yongqun
Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, United States.
Unit for Laboratory Animal Medicine, Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI, United States.
Front Immunol. 2017 Oct 26;8:1382. doi: 10.3389/fimmu.2017.01382. eCollection 2017.
With many protective vaccine antigens reported in the literature and verified experimentally, how to use the knowledge mined from these antigens to support rational vaccine design and study underlying design mechanism remains unclear. In order to address the problem, a systematic bioinformatics analysis was performed on 291 Gram-positive and Gram-negative bacterial protective antigens with experimental evidence manually curated in the Protegen database. The bioinformatics analyses evaluated included subcellular localization, adhesin probability, peptide signaling, transmembrane α-helix and β-barrel, conserved domain, Clusters of Orthologous Groups, and Gene Ontology functional annotations. Here we showed the critical role of adhesins, along with subcellular localization, peptide signaling, in predicting secreted extracellular or surface-exposed protective antigens, with mechanistic explanations supported by functional analysis. We also found a significant negative correlation of transmembrane α-helix to antigen protectiveness in Gram-positive and Gram-negative pathogens, while a positive correlation of transmembrane β-barrel was observed in Gram-negative pathogens. The commonly less-focused cytoplasmic and cytoplasmic membrane proteins could be potentially predicted with the help of other selection criteria such as adhesin probability and functional analysis. The significant findings in this study can support rational vaccine design and enhance our understanding of vaccine design mechanisms.
文献中报道了许多保护性疫苗抗原并经过实验验证，然而如何利用从这些抗原中挖掘的知识来支持合理的疫苗设计并研究潜在的设计机制仍不明确。为了解决这一问题，我们对Protegen数据库中手动整理的291种具有实验证据的革兰氏阳性和革兰氏阴性细菌保护性抗原进行了系统的生物信息学分析。所评估的生物信息学分析包括亚细胞定位、粘附素概率、肽信号传导、跨膜α螺旋和β桶、保守结构域、直系同源簇以及基因本体功能注释。在此我们展示了粘附素以及亚细胞定位、肽信号传导在预测分泌型细胞外或表面暴露的保护性抗原中的关键作用，并通过功能分析给出了机理解释。我们还发现，在革兰氏阳性和革兰氏阴性病原体中，跨膜α螺旋与抗原保护性呈显著负相关，而在革兰氏阴性病原体中观察到跨膜β桶与抗原保护性呈正相关。借助粘附素概率和功能分析等其他选择标准，可能会对通常较少关注的细胞质和细胞质膜蛋白进行预测。本研究中的重要发现能够支持合理的疫苗设计，并增进我们对疫苗设计机制的理解。
