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8 December 2010 Richard H. Scheuermann, Ph.D. Department of Pathology

Bioinformatics Resource Centers Influenza Research Database (IRD) Virus Pathogen Database and Analysis Resource ( ViPR ). 8 December 2010 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center. NIAID Scientific Resources.

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8 December 2010 Richard H. Scheuermann, Ph.D. Department of Pathology

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  1. Bioinformatics Resource CentersInfluenza Research Database (IRD)Virus Pathogen Database and Analysis Resource (ViPR) 8 December 2010 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center

  2. NIAID Scientific Resources http://www.niaid.nih.gov/labsandresources/resources/Pages/default.aspx

  3. DMID Resources List

  4. DMID BRC Resources

  5. Category A Pathogens

  6. Category B Pathogens

  7. Category A Pathogens

  8. DMID BRC Resources

  9. BRC Portal

  10. ViPR www.viprbrc.org

  11. Influenza Research Database (IRD) www.fludb.org

  12. IRD Home Page

  13. Public Health Impact of Influenza • Seasonal flu epidemics occur yearly during the fall/ winter months and result in 3-5 million cases of severe illness worldwide. • More than 200,000 people are hospitalized each year with seasonal flu-related complications in the U.S. • Approximately 36,000 deaths occur due to seasonal flu each year in the U.S. • Populations at highest risk are children under age 2, adults age 65 and older, and groups with other comorbidities. Source: World Health Organization - http://www.who.int/mediacentre/factsheets/fs211/en/index.html

  14. Known flu pandemics occurring during the 20th and 21st centuries 1) 1918 flu pandemic (Spanish flu) - Subtype H1N1 - the most severe pandemic - estimated to have claimed between 2.5% to 5.0% of the world’s population (20 > 100 million deaths) 2) Asian flu (1957 - 1958) - Subtype H2N2 - 1 > 1.5 million deaths 3) Hong Kong flu (1968 - 1969) - Subtype H3N2 - between 750,000 and 1 million deaths 4) 2009 H1N1 - Subtype H1N1 - > 16,000 deaths as of March 2010

  15. Influenza Virus Orthomyxoviridae family Negative-strand RNA Segmented Enveloped 8 RNA segments encode 11 proteins Classified based on serology of HA and NA

  16. IRD Overview www.fludb.org

  17. IRD Data Data - sequence

  18. IRD Data Data - surveillance

  19. Implicit versus explicit semantics Surveillance detail page

  20. Strain detail page

  21. Segment detail page 1

  22. Segment detail page 2

  23. Segment search taxonomy gazeteer

  24. IRD Data Data – 3D protein structure

  25. 3D protein structure search results

  26. 3D Structures & Integration • Visualize protein structure in 3D • Display sequence conservation heat map 
on the structure • Highlight sequence features (epitopes, etc.) • Download highlighted protein structure image

  27. 3D Structure

  28. Analysis and Visualization Tools

  29. My Workbench

  30. IRD Summary • Funded by U.S. National Institute of Allergy and Infectious Diseases (NIAID) • Free and open access with no use restrictions • Developed by a team of research scientists, bioinformaticians and professional software developers • Comprehensive collection of public data • Novel derived data, novel analytical tools, unique functions • Integration – Integration – Integration • www.fludb.org

  31. U.T. Southwestern Richard Scheuermann Burke Squires JyothiNoronha Victoria Hunt ShubhadaGodbole Brett Pickett Mengya Liu MSSM Adolfo Garcia-Sastre Eric Bortz Gina Conenello Peter Palese Vecna Chris Larsen Al Ramsey LANL Catherine Macken Mira Dimitrijevic U.C. Davis Nicole Baumgarth Northrop Grumman Ed Klem Mike Atassi Kevin Biersack Jon Dietrich WenjieHua Wei Jen Sanjeev Kumar Xiaomei Li Zaigang Liu Jason Lucas Michelle Lu Bruce Quesenberry Barbara Rotchford Hongbo Su Bryan Walters JianjunWang Sam Zaremba LiweiZhou Acknowledgements • IRD SWG • Gillian Air, OMRF • Carol Cardona, Univ. Minnesota • Adolfo Garcia-Sastre, Mt Sinai • ElodieGhedin, Univ. Pittsburgh • Martha Nelson, Fogarty • Daniel Perez, Univ. Maryland • Gavin Smith, Duke Singapore • David Spiro, JCVI • Dave Stallknecht, Univ. Georgia • David Topham, Rochester • Richard Webby, St Jude • USDA • David Suarez • Sage Analytica • Robert Taylor • Lone Simonsen • CEIRS Centers

  32. SFVT approach Influenza A_NS1_nuclear-export-signal_137(10) Influenza A_NS1_alpha-helix_171(17) VT-1 I F D R L E T L I L VT-2 I F N R L E T L I L VT-3 I F D R L E T IV L VT-4 L F D Q L E T L VS VT-5 I F D R L E N L T L VT-6 I F N R L E A L I L VT-7 I Y D R L E T L I L VT-8 I F D R L E T L V L VT-9 I F D R L E NIVL VT-10 I F E R L E T L I L VT-11 L F D QM E T L VS • Identify regions of protein/gene with known structural or functional properties – Sequence Features (SF) • an alpha-helical region, the binding site for another protein, an enzyme active site, an immune epitope • Determine the extent of sequence variation for each SF by defining each unique sequence as a Variant Type (VT) • High-level, comprehensive grouping of all virus strains by VT membership for each SF independently

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