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首页> 外文期刊>Genomics >Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori
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Core proteome mediated therapeutic target mining and multi-epitope vaccine design for Helicobacter pylori

机译：核蛋白质介导的治疗目标采矿和幽门螺杆菌幽门螺杆菌的多表位疫苗设计

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Helicobacter pylori is a Gram-negative spiral-shaped bacterium that infects half of the human population worldwide and causes chronic inflammation. In the present study, we used the art of computational biology for therapeutic drug targets identification and a multi-epitope vaccine against multi-strains of H. pylori. For drug target identification, we used different tools and softwares to identify human non-homologous but pathogen essential proteins, with virulent properties and involved in unique metabolic pathways of H. pylori. For this purpose, the core proteome of 84 strains of H. pylori was retrieved from EDGAR 2.3 database. There were 59,808 proteins sequences in these strains. Duplicates and paralogous protein sequence removal was followed by human non-homologous protein miningPathogen essential and virulent proteins were subjected to pathway analysis Subcellular localization of the virulent proteins was predicted and druggability was also checked, leading to 30 druggable targets based on their similarity with the approved drug targets in Drugbank. For immunoinformatics analysis, we selected two outer membrane proteins (HPAKL86_RS06305 and HPSNT_RS00950) and subjected to determined immunogenic B and T-Cell epitopes. The B and T-Cell overlapped epitopes were selected to design 9 different vaccine constructs by using linkers and adjuvants. Least allergenic and most antigenic construct (C-8) was selected as a promiscuous vaccine to elicit host immune response. Cloning and in silico expression of the constructed vaccine (C-8) was done to produce a clone having the desired (gene) vaccine construct. In conclusion, the prioritized therapeutic targets for 84 strains of H.pylori will be useful for future therapy design. Vaccine design may also prove useful in the quest for targeting multi-strains of H. pylori in patients.
机译：幽门螺杆菌是一种革兰氏阴性螺旋形细菌，可感染全世界人口的一半，并导致慢性炎症。在本研究中，我们使用了用于治疗药物靶标鉴定的计算生物学艺术和针对多菌株H.幽门螺杆菌的多表位疫苗。对于药物目标鉴定，我们使用不同的工具和软件来鉴定人类非同源但病原体基本蛋白质，具有毒性特性并参与H. Pylori的独特代谢途径。为此目的，从Edgar 2.3数据库中检索84个H.幽门螺杆菌菌株的核心蛋白质组。这些菌株中有59,808个蛋白质序列。术语和寄生蛋白序列除去，然后进行人的非同源蛋白质挖掘，对致毒性蛋白质的途径分析进行病毒蛋白质的途径分析，并且还检查了可用性毒性，导致30种可用的目标与批准的相似性。药物银行的药物目标。对于免疫信息分析，我们选择了两个外膜蛋白（HPAKL86_RS06305和HPSNT_RS00950）并进行了确定的免疫原性B和T细胞表位。选择B和T细胞重叠的表位通过使用接头和佐剂设计9种不同的疫苗构建体。选择至少过敏和大多数抗原构建体（C-8）作为一种混杂的疫苗，以引发宿主免疫应答。克隆和在构建的疫苗（C-8）的硅表达中进行以制备具有所需（基因）疫苗构建体的克隆。总之，84株H.Pylori的优先治疗靶标可用于未来的治疗设计。疫苗设计也可以证明在患者中靶向幽门螺杆菌的多菌株。

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