Department of Biological Sciences and Institute of Structural and Molecular Biology, Birkbeck College, University of London, Malet Street, London WC1E 7HX, UK.
Bioinformatics. 2010 Jun 1;26(11):1403-8. doi: 10.1093/bioinformatics/btq160. Epub 2010 Apr 13.
Modelling antigenic shift in influenza A H3N2 can help to predict the efficiency of vaccines. The virus is known to exhibit sudden jumps in antigenic distance, and prediction of such novel strains from amino acid sequence differences remains a challenge.
From analysis of 6624 amino acid sequences of wild-type H3, we propose updates to the frequently referenced list of 131 amino acids located at or near the five identified antibody binding regions in haemagglutinin (HA). We introduce a class of predictive models based on the analysis of amino acid changes in these binding regions, and extend the principle to changes in HA1 as a whole by dividing the molecule into regional bands. Our results show that a range of simple models based on banded changes give better predictive performance than models based on the established five canonical regions and can identify a higher proportion of vaccine escape candidates among novel strains than a current state-of-the-art model.
对甲型 H3N2 流感的抗原转变进行建模有助于预测疫苗的效率。已知该病毒会突然出现抗原距离的跳跃,而根据氨基酸序列差异预测此类新型菌株仍然是一个挑战。
通过对 6624 个野生型 H3 的氨基酸序列进行分析,我们对经常被引用的位于血凝素 (HA) 中或附近的 131 个氨基酸的列表进行了更新,这些氨基酸位于五个已确定的抗体结合区域。我们引入了一类基于对这些结合区域中的氨基酸变化分析的预测模型,并通过将分子划分为区域带将该原理扩展到整个 HA1 的变化上。我们的研究结果表明,一系列基于带状变化的简单模型比基于五个经典区域的模型具有更好的预测性能,并且可以比当前最先进的模型在新型菌株中识别出更高比例的疫苗逃逸候选株。