Bioinformatics Multidisciplinary Environment, Universidade Federal do Rio Grande Do Norte-UFRN, Natal, Brazil.
Department of Biochemistry, Universidade Federal do Rio Grande do Norte-UFRN, Natal, Brazil.
Front Immunol. 2020 May 5;11:816. doi: 10.3389/fimmu.2020.00816. eCollection 2020.
In reverse vaccinology approaches, complete proteomes of bacteria are submitted to multiple computational prediction steps in order to filter proteins that are possible vaccine candidates. Most available tools perform such analysis only in a single strain, or a very limited number of strains. But the vast amount of genomic data had shown that most bacteria contain pangenomes, i.e., their genomic information contains core, conserved genes, and random accessory genes specific to each strain. Therefore, in reverse vaccinology methods it is of the utmost importance to define core proteins and core epitopes. EpitoCore is a decision-tree pipeline developed to fulfill that need. It provides surfaceome prediction of proteins from related strains, defines core proteins within those, calculate their immunogenicity, predicts epitopes for a given set of MHC alleles defined by the user, and then reports if epitopes are located extracellularly and if they are conserved among the core homologs. Pipeline performance is illustrated by mining peptide vaccine candidates in strains. From a total proteome of ~4,800 proteins per strain, EpitoCore predicted 103 highly immunogenic core homologs located at cell surface, many of those related to virulence and drug resistance. Conserved epitopes identified among these homologs allows the users to define sets of peptides with potential to immunize the largest coverage of tested HLA alleles using peptide-based vaccines. Therefore, EpitoCore is able to provide automated identification of conserved epitopes in bacterial pangenomic datasets.
在反向疫苗学方法中,细菌的完整蛋白质组经过多个计算预测步骤的筛选,以过滤出可能的疫苗候选物。大多数可用的工具仅在单个菌株或非常有限数量的菌株中执行此类分析。但是,大量的基因组数据表明,大多数细菌都含有泛基因组,即它们的基因组信息包含核心、保守基因以及每个菌株特有的随机辅助基因。因此,在反向疫苗学方法中,定义核心蛋白和核心表位至关重要。EpitoCore 是一个决策树管道,用于满足这一需求。它提供了来自相关菌株的蛋白质表面组预测,定义了其中的核心蛋白,计算它们的免疫原性,为用户定义的一组给定的 MHC 等位基因预测表位,然后报告表位是否位于细胞外以及它们在核心同源物中是否保守。通过挖掘 株的肽疫苗候选物来说明管道性能。从每个菌株约 4800 种蛋白质的全蛋白质组中,EpitoCore 预测了 103 种高度免疫原性的核心同源物,这些同源物中的许多与毒力和耐药性有关。在这些同源物中鉴定出的保守表位允许用户定义具有潜在免疫测试 HLA 等位基因最大覆盖率的肽集合,使用基于肽的疫苗进行免疫。因此,EpitoCore 能够在细菌泛基因组数据集中自动识别保守表位。