1. www.viprbrc.org Virus Pathogen Resource (ViPR) 26 September 2011 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center

2. www.viprbrc.org ViPR Overview www.viprbrc.org

3. Virus Taxonomy Browser

4. www.viprbrc.org ViPR Usage

5. www.viprbrc.org ViPR Overview www.viprbrc.org

6. Database Search

7. www.viprbrc.org Virus-specific Details

8. www.viprbrc.org Search Page

9. www.viprbrc.org Search Results

10. www.viprbrc.org Strain Information

11. www.viprbrc.org Clinical Metadata

12. www.viprbrc.org Genome Data

13. www.viprbrc.org Gene/Protein Data

14. www.viprbrc.org Domain/Motif Annotation

15. www.viprbrc.org ViPR Overview www.viprbrc.org

16. Analysis Tools

17. www.viprbrc.org Genome Annotator

18. www.viprbrc.org ViPR Overview www.viprbrc.org

19. Workbench

20. www.viprbrc.org Sequence => Tools

21. www.viprbrc.org Meta-CATS

22. www.viprbrc.org Group Assignment

23. www.viprbrc.org Meta-CATS Result

24. www.viprbrc.org Workbench Updated

25. www.viprbrc.org ViPR Challenges Diverse research communities Diverse genome structures Variable quality of gene/protein annotations Deviation from the one gene – one functional protein paradigm (polyproteins) Growing complexity and inconsistency of metadata Driving Biological Projects taking us in a new direction that focuses on host genes

26. www.viprbrc.org DIVERSE GENOME STRUCTURES

27. www.viprbrc.org Large DNA Virus Genome

28. www.viprbrc.org Genome Browser for DNA Viruses

29. www.viprbrc.org Single Strand RNA Virus Genome

30. www.viprbrc.org INCOMPLETE/INCONSISTENT GENE/PROTEIN ANNOTATIONS

31. www.viprbrc.org Domain/Motif Annotation

32. www.viprbrc.org Incomplete Annotation

33. www.viprbrc.org Incomplete Annotation

34. www.viprbrc.org Gene/Protein Data

35. www.viprbrc.org Scaling Manual Curation

36. www.viprbrc.org POLYPROTEINS

37. www.viprbrc.org Gene/Protein Data

38. www.viprbrc.org COMPLEXITY OF CLINICAL METADATA

39. www.viprbrc.org Growing Clinical Metadata

40. www.viprbrc.org Complex Query Pages

41. www.viprbrc.org DBP AND HOST GENE DATA

42. www.viprbrc.org ViPR Driving Biological Projects Abraham Brass, Mass. General Hospital – Creation of a Dengue virus-host interaction database using functional genomics and bioinformatics Lynn Enquist / Moriah Szpara, Princeton University – Deep Sequencing and Neuronal Microarrays for Functional Genomic Analysis of Herpes Simplex Virus

43. www.viprbrc.org Brass (DENV) DBP – Lab Component Carry out whole-genome screens with multiple siRNA libraries Validate DENV host factor “hits” w/ RT-PCR Perform viral lifecycle and primary cell experiments on candidate genes

44. www.viprbrc.org Brass (DENV) DBP – ViPR Component Providing Data storage – Save “high-scoring” hits from the siRNA screens Associate virus life cycle data with the respective hits Developing Analytical Capability – Assist in assessing validity of lower confidence hits from screens – Over-representation of hits in biological pathways/networks Enhancing Resource Usability – Developing visualization strategy to interpret siRNA data (Interesting Gene Lists)

45. www.viprbrc.org Enquist/Szpara (HSV-1) DBP – Lab Component Obtain and assemble NGS data – Oral and encephalitic HSV-1 isolates Use gene expression microarrays to observe differences in human neuronal cells during a time course of infection Temporally dissect results by blocking infection at several phases – Entry, viral gene expression, and genome replication Test phenotype of loci predicted to contribute to neurovirulence – Swapping candidate gene(s)

46. www.viprbrc.org Enquist/Szpara (HSV-1) DBP – ViPR Component Providing Data storage – Import whole genome (consensus) sequences from GenBank – Import microarray results from GEO Associate virus life cycle data with respective genes Enhancing Resource Usability – Microarray data Make results searchable and cross reference with other related studies – Incorporate genome browser into resource Integrate genotype-phenotype data – Developing visualization strategy Interpret microarray results (Interesting Gene Lists)

47. www.viprbrc.org ViPR 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.viprbrc.org

48. ViPR Challenges Diverse research communities Diverse genome structures Variable quality of gene/protein annotations Deviation from the one gene – one functional protein paradigm (polyproteins) Growing complexity and inconsistency of metadata Driving Biological Projects taking us in a new direction that focuses on host genes

49. www.viprbrc.org ViPR Acknowledgements Univ. 0f Texas Southwestern – Richard Scheuermann PhD (PI) – Brett Pickett, PhD – Eva Sadat, PhD – Yun Zhang, MS Vecna Technologies – Chris Larsen, Ph.D. – Al Ramsey, Ph.D. Northrop Grumman – Mike Atassi, Program Manager – Ed Klem, Ph.D., Project Manager – Patty Berger – Jawwad Cheema – Jon Dietrich – Zhiping Gu, Ph.D. – Sherry He – Wenjie Hua – Wei Jen – Sanjeev Kumar – Xiaomei Li, Ph.D. – Jason Lucas – Bruce Quesenberry – Barbara Rotchford – Prabhu Shankar – Hongbo Su, Ph.D. – Bryan Walters – Sam Zaremba, Ph.D. – Liwei Zhou, Ph.D. NIAID / NIH – Andrei Gabrielian, Ph.D., Bioinformatics Program Officer Co-PI’s – Michael Gale, Ph.D. (University of Washington) – Jingming Ma, Ph.D. (University of Rochester Medical Center) Scientific Working Group – Richard Kuhn ( Purdue University) – Raul Andino ( University of California, San Francisco) – Slobodan Paessler ( University of Texas Medical Branch at Galveston) – X.J. Meng ( Virginia Polytechnic Institute and State University) – Colin Parrish ( Cornell University) – Elliot Lefkowitz ( University of Alabama, Birmingham) – Carla Kuiken ( Los Alamos National Laboratory) – David Knipe ( Harvard University) – Matthew Henn ( Broad Institute) – Richard Whitley ( University of Alabama, Birmingham) – John Young ( Salk Institute for Biological Studies) N01AI2008038

50. www.viprbrc.org 50 U.T. Southwestern – Richard Scheuermann (PI) – Burke Squires – Jyothi Noronha – Victoria Hunt – Shubhada Godbole – Brett Pickett – Yun Zhang 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 – Wenjie Hua – Wei Jen – Sanjeev Kumar – Xiaomei Li – Zaigang Liu – Jason Lucas – Michelle Lu – Bruce Quesenberry – Barbara Rotchford – Hongbo Su – Bryan Walters – Jianjun Wang – Sam Zaremba – Liwei Zhou IRD SWG – Gillian Air, OMRF – Carol Cardona, Univ. Minnesota – Adolfo Garcia-Sastre, Mt Sinai – Elodie Ghedin, 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 Acknowledgments N01AI40041