The Virus Pathogen Database and Analysis Resource (ViPR, www.ViPRbrc.org) is an integrated repository of data and analysis tools for multiple virus families, supported by the National Institute of Allergy and Infectious Diseases (NIAID) Bioinformatics Resource Centers (BRC) program. ViPR contains information for human pathogenic viruses belonging to the Arenaviridae, Bunyaviridae, Caliciviridae, Coronaviridae, Flaviviridae, Filoviridae, Hepeviridae, Herpesviridae, Paramyxoviridae, Picornaviridae, Poxviridae, Reoviridae, Rhabdoviridae and Togaviridae families, with plans to support additional virus families in the future. ViPR captures various types of information, including sequence records, gene and protein annotations, 3D protein structures, immune epitope locations, clinical and surveillance metadata and novel data derived from comparative genomics analysis. Analytical and visualization tools for metadata-driven statistical sequence analysis, multiple sequence alignment, phylogenetic tree construction, BLAST comparison and sequence variation determination are also provided. Data filtering and analysis workflows can be combined and the results saved in personal ‘Workbenches’ for future use. ViPR tools and data are available without charge as a service to the virology research community to help facilitate the development of diagnostics, prophylactics and therapeutics for priority pathogens and other viruses.

Please cite this paper as: Squires et al. (2012) Influenza research database: an integrated bioinformatics resource for influenza research and surveillance. Influenza and Other Respiratory Viruses 6(6), 404–416.BackgroundThe recent emergence of the 2009 pandemic influenza A/H1N1 virus has highlighted the value of free and open access to influenza virus genome sequence data integrated with information about other important virus characteristics.DesignThe Influenza Research Database (IRD, http://www.fludb.org) is a free, open, publicly-accessible resource funded by the U.S. National Institute of Allergy and Infectious Diseases through the Bioinformatics Resource Centers program. IRD provides a comprehensive, integrated database and analysis resource for influenza sequence, surveillance, and research data, including user-friendly interfaces for data retrieval, visualization and comparative genomics analysis, together with personal log in-protected ‘workbench’ spaces for saving data sets and analysis results. IRD integrates genomic, proteomic, immune epitope, and surveillance data from a variety of sources, including public databases, computational algorithms, external research groups, and the scientific literature.ResultsTo demonstrate the utility of the data and analysis tools available in IRD, two scientific use cases are presented. A comparison of hemagglutinin sequence conservation and epitope coverage information revealed highly conserved protein regions that can be recognized by the human adaptive immune system as possible targets for inducing cross-protective immunity. Phylogenetic and geospatial analysis of sequences from wild bird surveillance samples revealed a possible evolutionary connection between influenza virus from Delaware Bay shorebirds and Alberta ducks.ConclusionsThe IRD provides a wealth of integrated data and information about influenza virus to support research of the genetic determinants dictating virus pathogenicity, host range restriction and transmission, and to facilitate development of vaccines, diagnostics, and therapeutics.

The Influenza Research Database (IRD) is a U.S. National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Bioinformatics Resource Center dedicated to providing bioinformatics support for influenza virus research. IRD facilitates the research and development of vaccines, diagnostics and therapeutics against influenza virus by providing a comprehensive collection of influenza-related data integrated from various sources, a growing suite of analysis and visualization tools for data mining and hypothesis generation, personal workbench spaces for data storage and sharing, and active user community support. Here, we describe the recent improvements in IRD including the use of cloud and high performance computing resources, analysis and visualization of user-provided sequence data with associated metadata, predictions of novel variant proteins, annotations of phenotype-associated sequence markers and their predicted phenotypic effects, hemagglutinin (HA) clade classifications, an automated tool for HA subtype numbering conversion, linkouts to disease event data and the addition of host factor and antiviral drug components. All data and tools are freely available without restriction from the IRD website at https://www.fludb.org.

A protein activity has been identified in extracts of coated vesicles that enables purified clathrin triskelions to reassemble in vitro into coat structures of uniform size. Coats formed in the presence of this preparation, regardless of the buffer system employed, are uniform in size with a mean diameter of 78 nm (+5 nm SD) and a sedimentation coefficient (S2o, w) of ---250S. Analysis of the reassembled coats on dodecyl sulfate acrylamide gels reveals that they have specifically incorporated three polypeptides from the preparation: those of Mr 52,000, 100,000, and 110,000. The 52,000-, 100,000-, and 110,000-mol-wt polypeptides are incorporated in molar ratios of 0.85, 1.11, and 0.26, respectively, per three clathrin monomers (equivalent to one triskelion). We therefore designate these as assembly polypeptides (AP). In contrast, coats formed from clathrin alone, under permissive buffer conditions, are larger (400S), more heterogeneous in size (101 nm _ 15 nm SD), and are composed only of clathrin and its associated light chains. These biochemical and biophysical characteristics distinguish AP-reassembled coats from coats formed by triskelions alone.AP-reassembled coats can be isolated, dissociated, then reassembled in the absence of any other factors. This recycling indicates that all the information needed for reassembly is present in the coat-incorporated polypeptides themselves. Reassembly is stoichiometric and saturable with respect to both clathrin and AP concentration, in the presence of AP, significant coat reassembly occurs at clathrin concentrations as low as 0.06 mg/ml. AP-mediated reassembly proceeds at 4 °, 22 °, and 37°C. Coat formation also proceeds efficiently at intracellular pH values (7.2-7.5) in the presence of AP. In its absence, reassembly does not occur at all above pH 6.7. In summary, AP promotes clathrin reassembly into coat structures of uniform size and distinctive composition under physiologically relevant salt, temperature, and pH conditions. In addition, the close similarity in size between AP-reassembled coats in vitro and coated membranes in the Golgi region in vivo raises the possibility that AP in the cell may be associated with this subpopulation of coat structures.

These findings have implications in the development of specific second-generation cancer immunotherapy protocols.