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

ViPR Overview

Virus Taxonomy Browser

ViPR Usage

ViPR Overview

Database Search

Virus-specific Details

Search Page

Search Results

Strain Information

Clinical Metadata

Genome Data

Gene/Protein Data

Domain/Motif Annotation

ViPR Overview

Analysis Tools

Genome Annotator

ViPR Overview

Workbench

Sequence => Tools

Meta-CATS

Group Assignment

Meta-CATS Result

Workbench Updated

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

DIVERSE GENOME STRUCTURES

Large DNA Virus Genome

Genome Browser for DNA Viruses

Single Strand RNA Virus Genome

INCOMPLETE/INCONSISTENT GENE/PROTEIN ANNOTATIONS

Domain/Motif Annotation

Incomplete Annotation

Incomplete Annotation

Gene/Protein Data

Scaling Manual Curation

POLYPROTEINS

Gene/Protein Data

COMPLEXITY OF CLINICAL METADATA

Growing Clinical Metadata

Complex Query Pages

DBP AND HOST GENE DATA

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

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

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)

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)

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)

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

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

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) N01AI

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