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

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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. - PowerPoint PPT Presentation

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Page 1: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

Virus Pathogen Resource(ViPR)

26 September 2011

Richard H. Scheuermann, Ph.D.Department of Pathology

U.T. Southwestern Medical Center

Page 2: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR Overview

www.viprbrc.org

Page 3: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgVirus Taxonomy Browser

Page 4: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR Usage

Page 5: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR Overview

www.viprbrc.org

Page 6: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgDatabase Search

Page 7: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgVirus-specific Details

Page 8: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgSearch Page

Page 9: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgSearch Results

Page 10: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgStrain Information

Page 11: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgClinical Metadata

Page 12: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGenome Data

Page 13: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGene/Protein Data

Page 14: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgDomain/Motif Annotation

Page 15: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR Overview

www.viprbrc.org

Page 16: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgAnalysis Tools

Page 17: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGenome Annotator

Page 18: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR Overview

www.viprbrc.org

Page 19: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgWorkbench

Page 20: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgSequence => Tools

Page 21: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgMeta-CATS

Page 22: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGroup Assignment

Page 23: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgMeta-CATS Result

Page 24: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgWorkbench Updated

Page 25: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR 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

Page 26: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

DIVERSE GENOME STRUCTURES

Page 27: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgLarge DNA Virus Genome

Page 28: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

Genome Browser for DNA Viruses

Page 29: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

Single Strand RNA Virus Genome

Page 30: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

INCOMPLETE/INCONSISTENTGENE/PROTEIN ANNOTATIONS

Page 31: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgDomain/Motif Annotation

Page 32: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgIncomplete Annotation

Page 33: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgIncomplete Annotation

Page 34: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGene/Protein Data

Page 35: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgScaling Manual Curation

Page 36: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

POLYPROTEINS

Page 37: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGene/Protein Data

Page 38: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

COMPLEXITY OF CLINICAL METADATA

Page 39: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgGrowing Clinical Metadata

Page 40: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgComplex Query Pages

Page 41: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

DBP AND HOST GENE DATA

Page 42: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR 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

Page 43: Virus Pathogen Resource ( ViPR )

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

Page 44: Virus Pathogen Resource ( ViPR )

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)

Page 45: Virus Pathogen Resource ( ViPR )

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)

Page 46: Virus Pathogen Resource ( ViPR )

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)

Page 47: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR 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

Page 48: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR 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

Page 49: Virus Pathogen Resource ( ViPR )

www.viprbrc.orgViPR 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)

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Page 50: Virus Pathogen Resource ( ViPR )

www.viprbrc.org

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• 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

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