Richard H. Scheuermann, Ph.D. Department of Pathology, UT Southwestern March 30, 2011

1. Virus Bioinformatics Resource Centers – ViPR & IRD Richard H. Scheuermann, Ph.D. Department of Pathology, UT Southwestern March 30, 2011

2. Take home messages • NIAID Bioinformatics Resource Centers • Virus Pathogen Resource (ViPR; www.viprbrc.org ) • Influenza Research Database (IRD; www.fludb.org ) • Free and open access virus database and analysis resources • Comprehensive data collection • Sequence, structure, function, phenotype, surveillance, clinical, immune response • Integrated • Surveillance metadata with sequence • Sequence features and sequence conservation with protein structures • Development and adoption of data standards • Data sharing infrastructure and policies • Novel approach to identification of genetic determinants of important virus characteristics • Influenza NS1 nuclear export signal and host range

3. NIAID Research Resources

4. DMID Resources

5. DMID Resources List

6. BRCs

7. Category A Pathogens

8. Category B Pathogens

9. Category C Pathogens

10. Pathogen Portal pathogenportal.net

11. ViPR Resource

12. Home page www.viprbrc.org

13. 13 virus families

14. Taxonomy browser

15. Taxonomy browser expanded

16. Genome statistics

17. Search, analyze and save

18. Search

19. Analysis

20. Workbench

21. Data Integration

22. IRD www.fludb.org

24. Data Standards

25. CEIRS Network

27. Other Data Standards • Non-human mammalian surveillance • Virus isolate characteristics • Immuno-assays • Virus passage • Virus nomenclature • Clinical data

28. Surveillance

38. Data Sharing

39. Policies • Sequences – 30 days • Initial Surveillance Record – 90 days • Completed Virus Isolated Record – 1 year

40. Submission Infrastructure

43. Do variations in NS1 sequence featureS influence influenza virus host range?

44. 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) • alpha-helical region, host protein binding site, enzyme active site, 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 • Genotype-phenotype association statistical analysis (virulence, pathogenesis, host range, immune evasion, drug resistance) • While phylogenetics reflect evolutionary history of the virus, it is the focused regions in the viral genes/proteins that effect protein expression, structure and/or protein function that are responsible for important virus characteristics

45. Influenza A Sequence Features as of January 2011

46. ViPRSFVTs • Starting with 3 species • DENV = 192 SF’s • HCV = 335 SF’s • Pox = 14 genes, 295 total SF’s • HSV coming soon w/ DBP • Beginning automatic definition for other virus families • Most SF’s pulled from • UniProtKB protein annotations • IEDB immune epitopes (future)

47. NS1 Sequence Features

48. VT for SF8 (nuclear export signal)

49. VT-1 strains

50. VT for SF8 (nuclear export signal)