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Virus Pathogen Resource ( ViPR )

Virus Pathogen Resource ( ViPR ). 26 September 2011 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center. ViPR Overview. www.viprbrc.org. Virus Taxonomy Browser. ViPR Usage. ViPR Overview. www.viprbrc.org. Database Search. Virus-specific Details.

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Virus Pathogen Resource ( ViPR )

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

  2. ViPR Overview www.viprbrc.org

  3. Virus Taxonomy Browser

  4. ViPR Usage

  5. ViPR Overview www.viprbrc.org

  6. Database Search

  7. Virus-specific Details

  8. Search Page

  9. Search Results

  10. Strain Information

  11. Clinical Metadata

  12. Genome Data

  13. Gene/Protein Data

  14. Domain/Motif Annotation

  15. ViPR Overview www.viprbrc.org

  16. Analysis Tools

  17. Genome Annotator

  18. ViPR Overview www.viprbrc.org

  19. Workbench

  20. Sequence => Tools

  21. Meta-CATS

  22. Group Assignment

  23. Meta-CATS Result

  24. Workbench Updated

  25. 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. Diverse Genome Structures

  27. Large DNA Virus Genome

  28. Genome Browser for DNA Viruses

  29. Single Strand RNA Virus Genome

  30. Incomplete/InconsistentGene/Protein Annotations

  31. Domain/Motif Annotation

  32. Incomplete Annotation

  33. Incomplete Annotation

  34. Gene/Protein Data

  35. Scaling Manual Curation

  36. Polyproteins

  37. Gene/Protein Data

  38. Complexity of Clinical Metadata

  39. Growing Clinical Metadata

  40. Complex Query Pages

  41. DBP and Host Gene Data

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

  43. 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. 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. 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. 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. 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. 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 • JawwadCheema • Jon Dietrich • ZhipingGu, Ph.D. • Sherry He • WenjieHua • 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. U.T. Southwestern Richard Scheuermann (PI) Burke Squires JyothiNoronha Victoria Hunt ShubhadaGodbole 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 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 Acknowledgments • 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 N01AI40041

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