Analysis of viral diversity for vaccine target discovery

Abstract

BackgroundViral vaccine target discovery requires understanding the diversity of both the virus and the human immune system. The readily available and rapidly growing pool of viral sequence data in the public domain enable the identification and characterization of immune targets relevant to adaptive immunity. A systematic bioinformatics approach is necessary to facilitate the analysis of such large datasets for selection of potential candidate vaccine targets.ResultsThis work describes a computational methodology to achieve this analysis, with data of dengue, West Nile, hepatitis A, HIV-1, and influenza A viruses as examples. Our methodology has been implemented as an analytical pipeline that brings significant advancement to the field of reverse vaccinology, enabling systematic screening of known sequence data in nature for identification of vaccine targets. This includes key steps (i) comprehensive and extensive collection of sequence data of viral proteomes (the virome), (ii) data cleaning, (iii) large-scale sequence alignments, (iv) peptide entropy analysis, (v) intra- and inter-species variation analysis of conserved sequences, including human homology analysis, and (vi) functional and immunological relevance analysis.ConclusionThese steps are combined into the pipeline ensuring that a more refined process, as compared to a simple evolutionary conservation analysis, will facilitate a better selection of vaccine targets and their prioritization for subsequent experimental validation.Electronic supplementary materialThe online version of this article (10.1186/s12920-017-0301-2) contains supplementary material, which is available to authorized users.

Understanding dengue virus evolution to support epidemic surveillance and counter-measure development

“…Investigation of the protein structure(s) of the dengue genes has allowed for inferences to be made about impacts to protein function such as virion shape dynamics (or breathing), binding site availability, roles in replication and virulence, and variation at defined epitopes (Table 1). Examination of entropy (disorder/variability) plots across the entire DENV proteome (Fig 1) does offer a useful perspective on the functional and structural determinants of viral evolution and diversity.. Tracking changes in variability within a proteome (or genome) due to different selection pressures over time is informative to predicting potential impacts on vaccine design and studies of viral molecular epidemiology (discussed in detail in sections 8 and 11.2) [12,13]. For example, it is notable that several internal genes, such as NS1 and NS2a, are noted to have substantial diversity (Fig 1).…”

Pan-India novel coronavirus SARS-CoV-2 genomics and global diversity analysis in spike protein

“…Structural binding predictions suggests that prevalent mutation in spike RBD region, N439K did not overlap with currently characterized epitopes of neutralizing antibodies recovered from human convalescent patient 47 , 48 , 49 . The importance of tracking such mutations within RBM region is demonstrated by a recent study that identified mutations enabling escape from RBD-directed neutralizing antibodies [ 60 ]. Our data indicate that the none of the currently characterized mutations within RBM region escape the five RBM targeted neutralizing antibodies used in this study.…”

A bioinformatics potpourri

“… Phytoplankton and zooplankton image classification using a non-linear multiple kernel learning approach [ 40 ]. Immuno-informatics Computational methodology pipeline to process, predict and analyze potential T cell epitopes using influenza A, dengue, West Nile hepatitis A and HIV-1 virus sequence data [ 41 ]. NetCTL-bases predictions of HLA-A2, -A3 and -B7 supertype-restricted Zaire ebolavirus T cell epitope canidates [ 42 ].…”