Influenza Research Database (IRD): A Web-based Resource for Influenza Virus Data and Analysis

Victoria Hunt1*, R. Burke Squires1, Jyothi Noronha1, Brett Pickett1, Ed Klem3, Jon Dietrich3, Chris Larsen4 and Richard H. Scheuermann1,2 1Department of Pathology and 2Division of Biomedical Informatics, University of Texas Southwestern Medical Center, Dallas, Texas, United States 3Northrop Grumman Information Technology, Rockville, Maryland, United States; 4Vecna Technologies Inc., College Park, Maryland, United States

Introduction: The Influenza Research Database (IRD) Bioinformatics Resource Center (BRC) (www.fludb.org) is a free, publicly available resource that provides access to comprehensive, integrated data about influenza virus genome sequences, virus phenotypic characteristics and results from surveillance activities that serves as a platform for the discovery and development of influenza virus vaccines, diagnostics and therapeutics. IRD provides researchers access to user-friendly interfaces for data retrieval, data analysis, and visualization tools. Here we will present an overview of the IRD resource, detailing the integration of genomic data, proteomic data, immune epitopes, surveillance data, and other information that is useful in understanding virulence and host-pathogen interactions. Additionally, analysis tools for accomplishing such tasks as aligning multiple sequences, identifying sequence similarities and variations, determining phylogenetic relationships, visualization of protein structures and other features will also be described. Supported by U.S. National Institutes of Health N01AI40041.

IRD Homepage: The IRD homepage directs users to search pages, analysis and visualization tools, and their personal workbench for user-friendly navigation.

Search for Data in IRD: Find and retrieve various data types. Here a search is constructed for all Influenza A sequences from segment 4 of the H1N1 subtypes in the USA (2009 only) from all hosts.

Results: Summary results are returned in a tabular format that displays a list of records along with information about strain name, subtype, host species, year, etc.

Workbench: Researchers are able to store and organize information from previous searches and analyses into working sets by using their personal Workbench. The workbench enables working sets to be combined and/or shared with user-designated collaborators.

Analysis: After running a BLAST analysis using an A/California/04/2009 (H1N1) query sequence, a multiple sequence alignment (MUSCLE algorithm) was conducted for comparison against 2008 H1N1 subtypes in the USA from different host species. Alignments of the working set list were viewed in both an html format and in JalView. This assembled working set was also used to generate a phylogenetic tree using the HYK model.

3D Structure Visualization: Search and retrieve 3D protein structures for the influenza virus that have experimentally-determined epitopes obtained from the Immune Epitope Database (IEDB). Above is a display of hemagglutinin complexed with a neutralizing antibody. The experimentally-determined B-cell epitope with peptide sequence KRGPGSG is highlighted in yellow. Also highlighted is the conservation score where blue represents conserved regions and red represents non-conserved regions.

Other IRD Tools and Features: •  Sequence similarity search (BLAST) •  Geospatial representation of surveillance data

•  Experiment data •  Experimentally-determined and IRD predicted epitope data •  Phenotype searches •  Browse the database for structural and functional sequence features in influenza proteins using the Sequence Feature Variant Type search •  Identify point mutations •  Sequence annotation •  Data submission into IRD and tool to facilitate submission of new sequences to GenBank, and more….

Details Page: Upon selection of the A/California/04/2009, detailed information about this strain has been integrated onto one page for review.