Integrated Bioinformatics Data and Analysis Tools for Herpesviridae Viruses in the Virus Pathogen Resource (ViPR)

Yun Zhang1, Brett Pickett1, Eva Sadat2, , R. Burke Squires2, Jyothi Noronha2, Sanjeev Kumar3, Sam Zaremba3, Zhiping Gu3, Liwei Zhou3, Chris Larsen4, Wei Jen3, Edward B. Klem3, Richard H. Scheuermann1

1J. Craig Venter Institute, San Diego, CA; 2Department of Pathology, Univ. of Texas Southwestern Medical Center, Dallas, TX; 3Northrop Grumman Health Solutions, Rockville MD; 4Vecna Technologies, Greenbelt MD.

Introduction

Figure 2: A screenshot of the GBrowse window. The “Overview” panel displays the entire genome; the “Region” panel displays a portion of the genome surrounding a specified region; the “Details” panel displays several tracks of genomic features.

1 Pickett, B.E., et al. (2012) ViPR: an open bioinformatics database and analysis resource for virology research. Nucl. Acids Res. 40(D1): D593-D598

2Darling, A.C.E., et al. (2004) Mauve: Multiple Alignment of Conserved Genomic Sequence With Rearrangements. Genome Res., 14: 1394-1403

3Edgar, R.C. (2004) MUSCLE: multiple sequence alignment with high accuracy and high throughput.Nucleic Acids Res. 32(5):1792-1797.4Zmasek, C.M. and Eddy, S.R. (2001) ATV: display and manipulation of annotated phylogenetic trees. Bioinformatics, 17, 383-384.5Hanson, R. (2010) Jmol - a paradigm shift in crystallographic visualization. Journal of Applied Crystallography, 43, 1250-1260.

We would like to thank the primary data providers for the data that was used throughout this study. We also recognize the scientific and technical personnel responsible for supporting and developing ViPR, which has been wholly supported with federal funds from the NIH/NIAID (N01AI2008038 to R.H.S.).

Figure 6: 3D Protein Structure Viewer5 in ViPR. A display of a 3D protein structure for the Thymidine Kinase protein from Herpes Simplex Type 1 virus. Ligands, epitopes and active sites are highlighted (PDB ID: 1E2I).

ViPR combines the strength of a relational database with a suite of integrated bioinformatics tools to support everything from basic sequence and structural analyses to genotype-phenotype studies and host-virus interaction studies. The uniqueness of ViPR lies in:

• integrating data from various sources• capturing unique data on the host response to virus infection• combining the available tools to quickly perform complex

analytical workflows• facilitating rapid hypothesis generation using bioinformatics

methods for subsequent experimental testing• allowing data sharing and storage with collaborators

Figure 1: A screenshot of the ViPR homepageThe ViPR homepage is the portal used to access the various types of data and advanced functionality for any supported virus family.

The Virus Pathogen Database and Analysis Resource (ViPR, www.viprbrc.org), sponsored by the National Institute of Allergy and Infectious Diseases serves as a single publicly-accessible repository of integrated datasets and analysis tools for 14 different virus families including Herpesviridae to support wet-bench virology researchers focusing on the development of diagnostics, prophylactics, vaccines, and treatments for these pathogens1.

ViPR Supports 14 Virus FamiliesArenaviridae Flaviviridae PoxviridaeBunyaviridae Hepeviridae ReoviridaeCaliciviridae Herpesviridae RhabdoviridaeCoronaviridae Paramyxoviridae TogaviridaeFiloviridae Picornaviridae

ViPR Integrates Data from Many Sources• GenBank sequence records, gene annotations, and strain

metadata • Protein Databank (PDB) 3D protein structures• Immune epitopes from the Immune Epitope Database (IEDB)• Clinical data• Host Factor Data generated from the NIAID Systems Biology

projects and the ViPR-funded Driving Biological Projects• UniProtKB protein annotations• Gene Ontology (GO) classifications• Additional data derived from computational algorithms

ViPR Provides Analysis and Visualization Tools• Multiple Sequence Alignment• Phylogenetic Tree Construction• Sequence Polymorphism Analysis • Metadata-driven Comparative Genomics Statistical Analysis• Genome Annotator• Gbrowse Genome Viewer• Sequence Format Conversion • BLAST Sequence Similarity Search• 3D Protein Structure Visualization and Movie Generation• Sequence Feature Variant Type (SFVT) Analysis

ViPR enables you to store and share data and results through the ViPR Workbench

Figure 4: Comparative Genomic Analytical tools in ViPRA multiple sequence alignment of Human Herpesvirus 1 (HHV-1) (A) whole genome sequences2 and (B) VP16 nucleotide sequences3. (C) A phylogenetic tree visualized with the Archaeopteryx4 tool shows the relationship between HHV-1 VP16 proteins, red represents human while pink indicates unknown host. (D) The Metadata-driven Comparative Analysis Tool for Sequences uses statistics to identify individual positions that correlate with a specified metadata attribute.

A

C

D

Multiple Sequence Alignment,Phylogenetic Tree and Metadata-driven

Comparative Analysis Tool

3D Protein Structure Viewer

Summary

Acknowledgements

References

GBrowse for Genome Viewing• Provides both bird’s eye and detailed views of genomes and

genome annotations. • Available for Reference Sequences of Pox- and Herpes viruses.

Host-virus Interaction Data

Figure 5: Host Factor Data in ViPR. A host factor experiment result summary showing differentially expressed genes in human cells infected with SARS.

ViPR groups viral proteins into clusters based on predicted orthology within a virus taxon to facilitate gene/protein search, gene function inference, and virus evolution research.

Viral Protein Ortholog Groups

Figure 3: A screenshot of the Ortholog Group search result page. Each ortholog group name is linked to all viral proteins in the same ortholog cluster for the selected taxon.

ViPR is currently funding Driving Biological Projects to produce whole genome sequences for Human Herpesvirus 1 oral or neurotropic isolates. Lists of host genes that are differentially-expressed during infection of human neuronal cells will also be deposited.

B