Department of Bioinformatics, Biocenter, Am Hubland, D-97074 Wuerzburg, Germany.
Mol Omics. 2018 Oct 8;14(5):330-340. doi: 10.1039/c8mo00130h.
Borrelia burgdorferi is an extracellular spirochete that causes Lyme disease. Currently, no effective vaccine is available for humans and animals except for dogs. In the present study, an extensive bioinformatics pipeline was established to predict new candidates that can be used for vaccine development including building the protein-protein interaction network based on orthologues of experimentally verified protein-protein interaction networks, elucidation of the proteins involved in the immune response, selection of the topologically-interesting proteins and their prioritization based on their antigenicity. Proteomic network analysis yielded an interactome network with 120 nodes with 97 interactions. Proteins were selected to obtain a subnet containing only the borrelial membrane proteins and immune-related host proteins. This strategy resulted in the selection of 15 borrelial targets, which were subjected to extensive bioinformatics analysis to predict their antigenic properties. Based on the strategy applied in this study the proteins encoded by erpX (ErpX proteins, UniProt ID: H7C7L6), erpL (ErpL protein, UniProt ID: H7C7M3) and erpY (ErpY protein, UniProt ID: Q9S0D9) are suggested as a novel set of vaccine targets to control Lyme disease. Moreover, five different tools were used to validate their antigenicity regarding B-cells. The combination of all these proteins in a vaccine should allow improved protection against Borrelia infection.
伯氏疏螺旋体是一种引起莱姆病的细胞外螺旋体。目前,除了狗以外,人类和动物都没有有效的疫苗。在本研究中,建立了一个广泛的生物信息学管道,以预测新的候选疫苗,包括基于实验验证的蛋白质-蛋白质相互作用网络的同源物构建蛋白质-蛋白质相互作用网络、阐明参与免疫反应的蛋白质、选择拓扑有趣的蛋白质及其基于抗原性的优先级排序。蛋白质组学网络分析得到了一个包含 120 个节点和 97 个相互作用的相互作用网络。选择蛋白质以获得仅包含疏螺旋体膜蛋白和免疫相关宿主蛋白的子网。该策略选择了 15 个疏螺旋体靶标,并对其进行了广泛的生物信息学分析,以预测其抗原特性。基于本研究中应用的策略,建议将编码 erpX(ErpX 蛋白,UniProt ID:H7C7L6)、erpL(ErpL 蛋白,UniProt ID:H7C7M3)和 erpY(ErpY 蛋白,UniProt ID:Q9S0D9)的蛋白作为一组新的疫苗靶点来控制莱姆病。此外,还使用了五种不同的工具来验证它们针对 B 细胞的抗原性。将所有这些蛋白质组合在疫苗中应该可以提高对伯氏疏螺旋体感染的保护作用。