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

www.viprbrc.orgViPR Overview

www.viprbrc.org

www.viprbrc.orgVirus Taxonomy Browser

www.viprbrc.orgViPR Usage

www.viprbrc.orgViPR Overview

www.viprbrc.org

www.viprbrc.orgDatabase Search

www.viprbrc.orgVirus-specific Details

www.viprbrc.orgSearch Page

www.viprbrc.orgSearch Results

www.viprbrc.orgStrain Information

www.viprbrc.orgClinical Metadata

www.viprbrc.orgGenome Data

www.viprbrc.orgGene/Protein Data

www.viprbrc.orgDomain/Motif Annotation

www.viprbrc.orgViPR Overview

www.viprbrc.org

www.viprbrc.orgAnalysis Tools

www.viprbrc.orgGenome Annotator

www.viprbrc.orgViPR Overview

www.viprbrc.org

www.viprbrc.orgWorkbench

www.viprbrc.orgSequence => Tools

www.viprbrc.orgMeta-CATS

www.viprbrc.orgGroup Assignment

www.viprbrc.orgMeta-CATS Result

www.viprbrc.orgWorkbench Updated

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

www.viprbrc.org

DIVERSE GENOME STRUCTURES

www.viprbrc.orgLarge DNA Virus Genome

www.viprbrc.org

Genome Browser for DNA Viruses

www.viprbrc.org

Single Strand RNA Virus Genome

www.viprbrc.org

INCOMPLETE/INCONSISTENTGENE/PROTEIN ANNOTATIONS

www.viprbrc.orgDomain/Motif Annotation

www.viprbrc.orgIncomplete Annotation

www.viprbrc.orgIncomplete Annotation

www.viprbrc.orgGene/Protein Data

www.viprbrc.orgScaling Manual Curation

www.viprbrc.org

POLYPROTEINS

www.viprbrc.orgGene/Protein Data

www.viprbrc.org

COMPLEXITY OF CLINICAL METADATA

www.viprbrc.orgGrowing Clinical Metadata

www.viprbrc.orgComplex Query Pages

www.viprbrc.org

DBP AND HOST GENE DATA

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

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

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)

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)

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)

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

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

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)

N01AI2008038

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