Negi Surendra S, Braun Werner
Bioinformatics. 2017 Apr 1;33(7):1014-1020. doi: 10.1093/bioinformatics/btw767.
The phenomenon of cross-reactivity between allergenic proteins plays an important role to understand how the immune system recognizes different antigen proteins. Allergen proteins are known to cross-react if their sequence comparison shows a high sequence identity which also implies that the proteins have a similar 3D fold. In such cases, linear sequence alignment methods are frequently used to predict cross-reactivity between allergenic proteins. However, the prediction of cross-reactivity between distantly related allergens continues to be a challenging task. To overcome this problem, we developed a new structure-based computational method, Cross-React, to predict cross-reactivity between allergenic proteins available in the Structural Database of Allergens (SDAP). Our method is based on the hypothesis that we can find surface patches on 3D structures of potential allergens with amino acid compositions similar to an epitope in a known allergen. We applied the Cross-React method to a diverse set of seven allergens, and successfully identified several cross-reactive allergens with high to moderate sequence identity which have also been experimentally shown to cross-react. Based on these findings, we suggest that Cross-React can be used as a predictive tool to assess protein allergenicity and cross-reactivity.
: Cross-React is available at: http://curie.utmb.edu/Cross-React.html.
变应原蛋白之间的交叉反应现象对于理解免疫系统如何识别不同的抗原蛋白起着重要作用。如果变应原蛋白的序列比较显示出高序列同一性，就已知它们会发生交叉反应，这也意味着这些蛋白具有相似的三维折叠结构。在这种情况下，线性序列比对方法经常被用于预测变应原蛋白之间的交叉反应。然而，预测远缘变应原之间的交叉反应仍然是一项具有挑战性的任务。为了克服这个问题，我们开发了一种新的基于结构的计算方法Cross-React，用于预测变应原结构数据库（SDAP）中可用的变应原蛋白之间的交叉反应。我们的方法基于这样一种假设，即我们可以在潜在变应原的三维结构上找到氨基酸组成与已知变应原中的表位相似的表面区域。我们将Cross-React方法应用于一组多样的七种变应原，并成功鉴定出几种具有高到中等序列同一性的交叉反应性变应原，这些变应原也已通过实验证明会发生交叉反应。基于这些发现，我们建议Cross-React可以用作评估蛋白质变应原性和交叉反应性的预测工具。
Cross-React可在以下网址获取：http://curie.utmb.edu/Cross-React.html。
