06 November 2011 Richard H. Scheuermann, Ph.D. Department of Pathology

1. www.viprbrc.org Influenza Research Database (IRD) & Virus Pathogen Resource (ViPR) Bioinformatics Resource Centers (BRCs) and support for Systems Biology data 06 November 2011 Richard H. Scheuermann, Ph.D. Department of Pathology U.T. Southwestern Medical Center

2. ViPR Overview www.viprbrc.org

3. IRD Overview www.fludb.org

4. Data Summary & Sources

5. Search Access to Data www.fludb.org

6. Data Types

7. Analysis and Visualization www.fludb.org

8. Analysis and Visualization Tools

9. Workbench Access www.fludb.org

10. Data Submission www.fludb.org

11. Data Submission Page

12. Systems Biology “Omics” Data

13. Overview of Systems Biology & DBP Projects • Four systems biology groups funded by NIAID, including: • Systems Virology (Michael Katze group, Univ. Washington) • Influenza H1N1 and H5N1 and SARS Coronavirus • statistical models, algorithms and software, raw and processed gene expression data, and proteomics data • Systems Influenza (Alan Aderem group, Institute for Systems Biology) • various Influenza viruses • microarray, mass spectrometry, and lipidomics data • ViPR Driving Biological Projects • Abraham Brass, Mass. General Hospital • Dengue virus host factor database from RNAi screen • Lynn Enquist / MoriahSzpara, Princeton University • Deep sequencing and neuronal microarrays for functional genomic analysis of Herpes Simplex Virus

14. Omics Data Andrew R. Joyce & Bernhard Ø. Palsson, Nature Reviews Molecular Cell Biology 7, 198-210 (March 2006)

15. Acknowledgement • Lynn Law, U. Washington • Richard Green, U. Washington • Jyothi Noronha, U.T. Southwestern • Eva Sadat, U.T. Southwestern • Brett Pickett, U.T. Southwestern

16. Discussion Points • Relationship between data archives (e.g. GEO, PRIDE) and the BRCs (e.g. IRD, ViPR, PATRIC) • Integration • Metadata standards • Metadata • What kind of data • What kind of standards – MIBBI vs. “MIBBI lite” • Raw versus processed data • Primary results data • Need to define what is considered “primary” data for each platform • Microarray example: raw image files (.tiff) vs probe intensity values (.cel) • Opportunity for re-processing leading to re-interpretation • Derived/processed results • “Interesting gene/protein lists” from microarray, RNAi, proteomics, and other experimental platforms • “Interesting metabolite lists” • Data processing metadata • Visualize and analyze “interesting gene/protein/metabolite lists”

17. Proposal for “Omics” Data • “Omics” data management (host) • Project metadata • Experiment metadata • Experiment sample metadata • Data analysis metadata • Primary results • Derived results (e.g. “interesting gene/protein/metabolite lists” (Host Factor Biosets)) • Add additional related datasets from other sources • Visualize Host Factor Biosets in context of biological pathways and networks • Statistical analysis of pathway sub-network overrepresentation • Re-analysis of primary data using assembled pipeline tools (?)

18. GEO Representation GEO data representations based on free text

19. Non-standard Descriptions Guess samples details

20. Metadata (MIBBI-compliant) • Project Level Metadata • Hypothesis, rationale, study design, etc. • Publications and links pertaining to the project • Data providers - PI, other key personnel, affiliations, contact information • Experiment/Assay Level Metadata • Experiment platform • Experiment data type • Experiment Sample Level Metadata • Sample source and characteristics of source • Sample type • Source/sample treatment information • Assay details • Data Processing/Analysis Level Metadata • Algorithm(s) used for transforming primary to derived data • Configuration parameters

21. Metadata Submission Modules Study Experiment Animal/human subject Biosample Reagent Protocol Experiment Sample Analysis method Host factor bioset

22. Study

23. Experiment

24. Subject

25. Biosample

26. Reagent

27. Protocol

28. Experiment Sample

29. Analysis Method

30. Host Factor Bioset

31. Possible Data Submission Workflows A B GEO free text metadata GEO free text metadata GEO GEO Primary results Primary results Primary results Study metadata Study metadata Experiment sample metadata Experiment sample metadata ViPR/IRD ViPR/IRD Analysis metadata Analysis metadata Host factor bioset Host factor bioset C Primary results Study metadata GEO free text metadata Experiment sample metadata ViPR/IRD GEO Analysis metadata Primary results Host factor bioset

32. About Us Supported Projects Announcements Resources Support ViPR . . . Virus Pathogen Resource FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME Genes & Proteins TEXT SEARCH Genomes Immune Epitopes Quick Text Search HISTORY Your Analysis History Host Factor Biosets SEARCH OR FIND: Search Analyze Save to Workbench • Search our robust database for: • Genomes • Genes & proteins • Immune epitopes • 3D protein structures • Analyze your results online. We offer: • Identify similar sequences (BLAST) • Align sequences (MSA) • Find short peptides in proteins • Visualize aligned sequences • Sign up for a Workbench to: • Store data in working sets for future analysis • Integrate ViPR data with your laboratory data • Store analysis results • Share results and data with collaborators Browse All Search Types Browse All Tools Sign Up! Sign In 3D Protein Structures Protein Domains Protein Motifs Sequence Feature Variant Type Ortholog Groups Retrieve a Download • Data SummaryUpdated 2 Weeks Ago Highlights ViPR Highlight for All Families You can now search for, and visualize, 3D protein structures from within the ViPR website. Simply navigate to the protein of interest and then follow the links to use this feature. View Tutorial View Example Results Start Search • Virus Taxonomy Browser Click on family or species of interest in taxonomy below to view viral genomes, or click here to view in list format. • Community Spotlight The ViPR database is pleased to announce the progress of the Driving Biological Projects (DBPs). As results become available, we will incorporate them into our database for easy access and use from the scientific community. ViPR welcomes feedback, contributions, and collaborations from the scientific community on how we can improve our resource.

33. About Us Supported Projects Announcements Resources Support ViPR Sign Out Virus Pathogen Resource You are logged in as username@domain.edu Back to Previous Page FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME Host Factor Biosets Please Select an Experiment to Explore to view the associated Bioset(Interesting Gene List ) Cite ViPR Tutorials Report a Bug Request Web Training Contact Us Release Date: Jan 7, 2012 This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

34. About Us Announcements Resources Support ViPR Sign Out Virus Pathogen Resource You are logged in as username@domain.edu FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME Download Host Factors Download Primary Results Download All Host Factor Biosets (“Omics” Experiment Details) HOST FACTOR BIOSETS PRIMARY RESULTS EXPERIMENT METADATA (from Host response to Influenza virus infection) - - +

35. About Us Announcements Resources Support ViPR Sign Out Virus Pathogen Resource You are logged in as username@domain.edu Host Factor Biosets (“Omics” Experiment Details) FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME EXPERIMENT METADATA (from Host response to Influenza virus infection) Download Host Factors Download Primary Results Download All PRIMARY RESULTS HOST FACTOR BIOSETS + + - Run Analysis  Cite ViPR Tutorials Report a Bug Request Web Training Contact Us Release Date: Jan 7, 2012 This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

36. About Us Announcements Resources Support ViPR Sign Out Virus Pathogen Resource You are logged in as username@domain.edu Host Factor Biosets (“Omics” Experiment Details) FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME EXPERIMENT METADATA (from Host response to Influenza virus infection) Download Host Factors Download Primary Results Download All PRIMARY RESULTS HOST FACTOR BIOSETS + + Run Analysis  - Visualize Protein Network Cite ViPR Tutorials Report a Bug Request Web Training Contact Us Release Date: Jan 7, 2012 This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

37. About Us Announcements Resources Support ViPR Sign Out Virus Pathogen Resource You are logged in as username@domain.edu Host Factor Biosets (“Omics” Experiment Details) FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME EXPERIMENT METADATA (from Host response to Influenza virus infection) Download Host Factors Download Primary Results Download All ViPR Protein-Protein Interactions and Pathway Visualization HOST FACTOR BIOSETS PRIMARY RESULTS + - Run Analysis  - Visualize Protein Network Please choose the type of data that you would like to view relating to your selection(s):  First-Degree (Direct) Interactions Second-Degree Interactions Functional Modules Metabolic Pathways    Cancel Visualize Cite ViPR Tutorials Report a Bug Request Web Training Contact Us Release Date: Jan 7, 2012 This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

38. About Us Announcements Resources Support ViPR Sign Out Virus Pathogen Resource You are logged in as username@domain.edu Visualize Host Factor Interactions FAMILY_NAME SEARCH DATA ANALYZE & VISUALIZE ACCESS WORKBENCH VIRUS FAMILIES HOME PROTEIN-PROTEIN INTERACTIONS INFORMATION Number of “hits” from Interesting Gene List: 1 Number of Nodes: $num_nodes Number of Edges: $num_edges Save Analysis Cite ViPR Tutorials Report a Bug Request Web Training Contact Us Release Date: Jan 20, 2011 This project is funded by the National Institute of Allergy and Infectious Diseases (NIH / DHHS) under Contract No. HHSN272200900041C and is a collaboration between Northrop Grumman Health IT, University of Texas Southwestern Medical Center and Vecna Technologies. Virus images courtesy of CDC Public Health Image Library and Wellcome Images.

39. U.T. Southwestern Richard Scheuermann (PI) Burke Squires JyothiNoronha Victoria Hunt Eva Sadat Brett Pickett Yun Zhang Vecna Chris Larsen Al Ramsey LANL Catherine Macken Mira Dimitrijevic U.C. Davis Nicole Baumgarth USDA David Suarez Sage Analytica Robert Taylor Lone Simonsen U. Washington Michael Gale Northrop Grumman Ed Klem Mike Atassi Jon Dietrich Patty Berger JawwadCheema ZhipingGu Sherry He WenjieHua Wei Jen Sanjeev Kumar Xiaomei Li Jason Lucas Bruce Quesenberry Barbara Rotchford Prabhu Shankar Hongbo Su Bryan Walters Sam Zaremba Liwei Zhou U. Washington Lynn Law Richard Green 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 • Dave Stallknecht, Univ. Georgia • David Topham, Rochester • Richard Webby, St Jude • ViPR SWG • Richard Kuhn, Purdue • Raul Andino, UCSF • Slobodan Paessler, UTMB Galveston • X.J. Meng, VBI • Colin Parrish, Cornell • Elliot Lefkowitz, UAB • Carla Kuiken, LANL • David Knipe, Harvard • Matthew Henn, Broad Institute • Richard Whitley, UAB • John Young, Salk Institute N01AI40041 N01AI2008038