期刊
JOURNAL OF BIOINFORMATICS AND COMPUTATIONAL BIOLOGY
卷 12, 期 5, 页码 -出版社
WORLD SCIENTIFIC PUBL CO PTE LTD
DOI: 10.1142/S0219720014500231
关键词
Conservation score; average amino acid conservation score; conserved epitope; broadly neutralizing antibody; structure alignment; location-based method; H7N9
类别
资金
- UTS Early Career Research Grant
- ARC Discovery Project [DP130102124]
- China Scholarship Council
A conserved epitope is an epitope retained by multiple strains of influenza as the key target of a broadly neutralizing antibody. Identification of conserved epitopes is of strong interest to help design broad-spectrum vaccines against influenza. Conservation score measures the evolutionary conservation of an amino acid position in a protein based on the phylogenetic relationships observed amongst homologous sequences. Here, Average Amino Acid Conservation Score (AAACS) is proposed as a method to identify HA's conserved epitopes. Our analysis shows that there is a clear distinction between conserved epitopes and nonconserved epitopes in terms of AAACS. This method also provides an excellent classification performance on an independent dataset. In contrast, alignment-based comparison methods do not work well for this problem, because conserved epitopes to the same broadly neutralizing antibody are usually not identical or similar. Location-based methods are not successful either, because conserved epitopes are located at both the less-conserved globular head (HA1) and the more-conserved stem (HA2). As a case study, two conserved epitopes on HA are predicted for the influenza A virus H7N9: One should match the broadly neutralizing antibodies CR9114 or FI6v3, while the other is new and requires validation by wet-lab experiments.
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