An integrated approach to epitope analysis II: A system for proteomic-scale prediction of immunological characteristics.
An integrated approach to epitope analysis II: A system for proteomic-scale prediction of immunological characteristics.
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DOI：
10.1186/1745-7580-6-8
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发表时间：
2010-11-02
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影响因子：
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通讯作者：
Homan, E Jane
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文献类型：
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作者：
Bremel, Robert D;Homan, E Jane
背景：提高我们对免疫反应的理解对于制定对抗多种疾病的策略至关重要。我们描述了一种基于氨基酸序列主成分分析的集成表位分析系统，使用多层感知器神经网络对 35 个 MHC-I 和 14 个 MHC-II 等位基因的肽结合亲和力进行 QSAR 回归预测。 结果：所描述的方法允许快速处理单个蛋白质、整个蛋白质组或其子集以及同一生物体的多个菌株。它可以考虑微生物多样性和宿主免疫遗传学的界面。结合亲和力模式与拓扑特征（例如细胞外或膜内位置）相关，并集成到图形显示中，有助于概念性地理解 B 细胞和 T 细胞介导的免疫的相互作用。应用这种方法产生的模式包括显示出与 MHC-I 和 MHC-II 高亲和力结合的肽之间的相关性，以及与预测的 B 细胞表位的相关性。这些被表征为一致表位组（CEG）。同样明显的是跨蛋白质的长程模式，这些模式识别了不同和杂合的 HLA 等位基因的排列群体的高亲和力结合区域，以及与个体 HLA 等位基因的 MHC 反应的细微差异，这对于疾病易感性以及疫苗和临床试验设计可能很重要。比较了应用 QSAR 方法得出的预测表位图谱与来自不同多物种数据集、金黄色葡萄球菌和牛痘病毒的实验得出的表位图谱。结论：具有交互式图形功能的桌面应用程序被证明是一个有用的平台，可用于开发表位图谱预测和可视化工具，其规模范围从单个蛋白质到来自生物体多个菌株的蛋白质组。讨论了观察到的肽表位模式可能的功能含义，包括它们对 B 细胞和 T 细胞合作和交叉呈递的影响。
BACKGROUND: Improving our understanding of the immune response is fundamental to developing strategies to combat a wide range of diseases. We describe an integrated epitope analysis system which is based on principal component analysis of sequences of amino acids, using a multilayer perceptron neural net to conduct QSAR regression predictions for peptide binding affinities to 35 MHC-I and 14 MHC-II alleles.RESULTS: The approach described allows rapid processing of single proteins, entire proteomes or subsets thereof, as well as multiple strains of the same organism. It enables consideration of the interface of diversity of both microorganisms and of host immunogenetics. Patterns of binding affinity are linked to topological features, such as extracellular or intramembrane location, and integrated into a graphical display which facilitates conceptual understanding of the interplay of B-cell and T-cell mediated immunity.Patterns which emerge from application of this approach include the correlations between peptides showing high affinity binding to MHC-I and to MHC-II, and also with predicted B-cell epitopes. These are characterized as coincident epitope groups (CEGs). Also evident are long range patterns across proteins which identify regions of high affinity binding for a permuted population of diverse and heterozygous HLA alleles, as well as subtle differences in reactions with MHCs of individual HLA alleles, which may be important in disease susceptibility, and in vaccine and clinical trial design. Comparisons are shown of predicted epitope mapping derived from application of the QSAR approach with experimentally derived epitope maps from a diverse multi-species dataset, from Staphylococcus aureus, and from vaccinia virus.CONCLUSIONS: A desktop application with interactive graphic capability is shown to be a useful platform for development of prediction and visualization tools for epitope mapping at scales ranging from individual proteins to proteomes from multiple strains of an organism. The possible functional implications of the patterns of peptide epitopes observed are discussed, including their implications for B-cell and T-cell cooperation and cross presentation.