tetano
Editor, Senior Moderator
J Bioinform Comput Biol. 2014 Aug 11:1450023. [Epub ahead of print]
Influenza A HA's conserved epitopes and broadly neutralizing antibodies: A prediction method.
Ren J1, Ellis J, Li J.
Author information
Abstract
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.
KEYWORDS:
Conservation score; H7N9; average amino acid conservation score; broadly neutralizing antibody; conserved epitope; location-based method; structure alignment
PMID:
25208658
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25208658
Influenza A HA's conserved epitopes and broadly neutralizing antibodies: A prediction method.
Ren J1, Ellis J, Li J.
Author information
Abstract
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.
KEYWORDS:
Conservation score; H7N9; average amino acid conservation score; broadly neutralizing antibody; conserved epitope; location-based method; structure alignment
PMID:
25208658
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25208658