title: Influenza A HA's conserved epitopes and broadly neutralizing antibodies: a prediction method.
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.
authors.affiliation: Advanced Analytics Institute, Faculty of Engineering and Information Technology, University of Technology Sydney, P. O. Box 123, Broadway, NSW 2007, Australia.
authors.forename: Jing
authors.initials: J
authors.lastname: Ren
authors.forename: John
authors.initials: J
authors.lastname: Ellis
authors.forename: Jinyan
authors.initials: J
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics*; D019295:Computational Biology; D017124:Conserved Sequence; D030562:Databases, Protein; D000939:Epitopes / Q000737:chemistry / Q000235:genetics*; D019143:Evolution, Molecular; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000235:genetics / Q000276:immunology; D009980:Influenza A virus / Q000235:genetics* / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology; D008958:Models, Molecular; D015233:Models, Statistical
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000956:Antigens, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus
keywords: Conservation score; H7N9; average amino acid conservation score; broadly neutralizing antibody; conserved epitope; location-based method; structure alignment