Systems Biology and Animal Models: STRIDE

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1 Systems Biology and Animal Models: STRIDE Michael G Katze, Ph.D. presentation to Eighth Comparative Medicine Resource Directors Meeting May 10th, 2010

2 Questions What Pandemics Are We Currently Experiencing? A) HIV/AIDS B) Hepatitis C C) Swine Flu (H1N1) D) All of the above

3 Answer: D - All of the above

4 TRUE or FALSE? We do NOT have an AIDS Vaccine?

5 TRUE OR FALSE? Something Has To Change

6 KEY POINTS-DEFINITIONS TO REMEMBER What Is Systems Biology? What Is STRIDE? Prototype for Enabling Researchers Growth in Primate Genomics New Directions through Collaboration Information Overload POST GENOMICS AGE Paradigm Shift-New Vocabulary

7 Denis Noble: The Music of Life: Biology beyond the Genome Systems biology...is about putting together rather than taking apart, integration rather than reduction. It requires that we develop ways of thinking about integration that are as rigorous as our reductionist programmes, but different...it means changing our philosophy, in the full sense of the term Oxford University Press, (8 Jun 2006)

8 Systems Biology Paradigm

9 Current NHP SYSTEMS BIOLOGY Research Efforts NHP Models of Respiratory Disease 2009 Swine-origin H1N1 Influenza A Expression Analysis by Arrays Proteomics Analysis Agilent Collaboration NextGen Sequencing ABI Collaboration 1918 Pandemic Influenza vs. Highly Pathogenic Avian Influenza (HPAI) HPAI vs. reassortants of 1918 Pandemic Influenza (Battelle Infection Model) Filovirus Studies Correlates of protection in Ebola vaccine studies AIDS Pathogenesis and Vaccine Related Studies Natural Infections in AGM SVEU Vaccine Study Differences among DNA Vaccine Regimens NIDA P01 Proteomics Center opiate impact on pathogenesis in natural host HVTN STEP Profiling Vaccinees vs. Placebo, with impact of Ad5 Immunity In vitro HIV/SIV Systems Biology in controlled experimental context

10 How Can We Best Apply Systems Biology Approaches To Achieve Our Goal Of Improving Human Health?

11 Experience We Have Had Success Putting Together And Participating In Large Multidisciplinary Programs. Pacific Northwest Regional Center of Excellence NIDA Center for Functional Genomics Systems Biology Contract This experience and infrastructure can be leveraged by STRIDE

Scientists As Well As Giving Them Access To A Systems Biology Toolkit. www.

12 STRIDE- E IS FOR ENABLE STRIDE Represents A Prototype Center For Simultaneously Performing Basic Research And Enabling Collaboration Between A Diverse Group Of Scientists As Well As Giving Them Access To A Systems Biology Toolkit. Stimulus money Multi-center helping effort to fund that STRIDE continues through to grow Training Grants

13 Participating Institutions

Focus on Translational Research Taken from the ITHS website T0 is characterized by the identification of opportunities and approaches to health problems.

14 Focus on Translational Research Taken from the ITHS website T0 is characterized by the identification of opportunities and approaches to health problems. T1 seeks to move basic discovery into a candidate health application. T2 assesses the value of application for health practice leading to the development of evidence-based guidelines. T3 attempts to move evidencebased guidelines into health practice, through delivery, dissemination, and diffusion research. T4 seeks to evaluate the real world health outcomes of population health practice.

15 New Community Context and Associations NCRR Informatics Initiative to integrate data and information on animal models Enable community to locate, identify, apply most useful animal models Anticipating WaNPRC and our Division as contributors to this effort Extensive knowledge of NHP models of viral diseases Extensive informatics infrastructure Advisory role in planning and resource prioritization Contributing role as generating models and linking to our genomics and other high-throughput data sets.

17 Collaborative Cross Mice Wide Range of Outcomes Percent Starting Mass 110 loss Weight Loss Virus challenge Days post challenge >400 genetically distinct strains

18 Acknowledgements - UNC Martin Ferris, Ralph Baric, Matt Frieman, Mark Heise, Fernando Pardo-Manuel de Villena

21 STRIDE RESOURCES

22 Current Collaborative Systems Biology Research Projects

23 New Collaborative Research Projects 1. Genomic profiling of pathogen-host interactions of oncogenic gammaherpesviruses in vivo. Timothy M. Rose, Ph.D. 2. Alterations of cellular metabolism by oncogenic herpesvirus. Michael Lagunoff, Ph.D. 3. BioGRID curation effort to systematically capture literature interactions and post-translational modifications for every human protein known to be either associated with or influenced by HIV-encoded factors. Mike Tyers, Ph.D. and Kara Dolinski, Ph.D. (Princeton University) Affiliated with LAMHDI

24 STRIDE Funding RC4 Recently Submitted

25 Leveraging STRIDE To Enhance Non- Human Primate Genomics Research

Growth in Primate Genomics Primate (2 (3 (4 nd rd th ) Seattle Genomics The Macaque International Workshop, Genome Conference January 2001 on on Primate Primate Genomics, Genomics, March April 2008

by project approximately Research Centers, 130 scientists Macaque NIH staff, from and Genome academia investigators and Attended by by more approximately than 190 scientists 170 scientists from

on Members genomics of and the evolutionary nonhuman primate biology, models primate of research, backgrounds Introduction of a Bioinformatics This Workshop enables to refinement expose nonhuman and

26 Growth in Primate Genomics Primate (2 (3 (4 nd rd th ) Seattle Genomics The Macaque International Workshop, Genome Conference January 2001 on on Primate Primate Genomics, Genomics, March April Consortium Publishes Attended In 2005, NHGRI by 90 participants initiates the that $20 included million dollar the Directors rhesus macaque of the eight National sequencing Attended Primate by project approximately Research Centers, 130 scientists Macaque NIH staff, from and Genome academia investigators and Attended by by more approximately than 190 scientists 170 scientists from diverse research working industry. on Members genomics of and the evolutionary nonhuman primate biology, models primate of research, backgrounds Introduction of a Bioinformatics This Workshop enables to refinement expose nonhuman and disease. genome sciences, AIDS, and infectious disease and biodefense primate Interest researchers in Bioinformatics to high-throughput Workshop improved so accuracy research much that tools of we macaquespecific and had making to cap communities This meeting, were the represented, first ever of its as kind, were was the productive NCRR Division and of registration sense of the data successful Comparative on Medicine multiple levels. and the First Office and of resources foremost, AIDS Research. as well as Caliber of Keynote speakers and attendees highlight it provided the success the of impetus Provided to NCRR a platform and NIH for roll-out critical to expand of newly data funding generated for comparative for research nonhuman previous conferences and increased interest in Primate Genomics in primate genomics. primate research tools including evolutionary macaque-specific genomics oligonucleotide microarrays.

27 Current Nonhuman Primate Genomics Efforts - STRIDE Reference RNA SEQ Transcriptome Project Born out of the 4 th International Primate Genomics Conference Collaboration between Industry (ILLUMINA-ABI (?)) and Academic Institutions Leveraging Next Generation Sequencing Technology Multiple tissues from ~12-18 nonhuman primate species of medical and evolutionary importance Data will be accessible by entire research community Genome 10K Project Steve O Brien et al (NCI) The Genome 10K project aims to assemble a genomic zoo a collection of DNA sequences representing the genomes of 10,000 vertebrate species How can we best leverage and intersect these two efforts? With help from STRIDE as a coordinating model, we will establish an international consortium on nonhuman primate genome sequencing

28 The World of Non- Human Primate Research Has Changed Forever

29 MOREOVER RUMOR HAS IT.. NHGRI Has Committed to Sequencing 30 Non- Human Primate Genomes?

31 IF NOT NIH THEN.?????

32 ALL OF THESE EFFORTS WILL BE GENERATING AN ENORMOUS AMOUNT OF DATA

33 Information Overload? New York Times April 2009

34 High-throughput Technologies are Generating an Unprecedented Amount of DATA How will researchers not currently involved with these technologies access and leverage this DATA? How will we ensure limited amounts of redundancy when generating genomic resources? How can we more quickly translate this DATA in to medical achievements? Role for BIRN? WITH TECHNOLOGY MOVING SO FAST, WE HAVE TO EVOLVE OUR PROCESS AND WAYS OF THINKING TO ACCOMMODATE AND TRANSLATE THE INFORMATION IN TO BETTER HUMAN HEALTH

35 The STRIDE Centers Goal Is To Enable Those Connections And Provide Access To The Appropriate Tools To achieve a truly systems level view utilizing highthroughput technologies, researchers from diverse backgrounds need to be connected and tools have to be put in place for effective interpretation and communication

36 Katze Lab Computational Biology Data Capture Data Access Statistical & Functional Analysis Integrative Analysis & Modeling Robust IT Infrastructure Scalable Computing Infrastructure LabKey Development Web Portal Development Enterprise Application Deployment Resolver / GeneData / GeneSpring Ingenuity IPA GeneGo MetaCore Spotfire DecisionSite Advanced Method Development NextGen Capability Host Response Compendium Multi-Omic Integrative Analysis Network Analysis

37 Robust IT Infrastructures Software Hardware

38 KEY POINTS-DEFINITIONS TO REMEMBER What Is Systems Biology? What Is STRIDE? Prototype for Enabling Researchers Growth in Primate Genomics New Directions through Collaboration Information Overload POST GENOMICS AGE Paradigm Shift-New Vocabulary

39 STRIDE-Solving The Puzzle Through Systems Biology Michael Katze

Synthetic Genomics and Its Application to Viral Infectious Diseases. Timothy Stockwell (JCVI) David Wentworth (JCVI)

Synthetic Genomics and Its Application to Viral Infectious Diseases Timothy Stockwell (JCVI) David Wentworth (JCVI) Outline Using informatics to predict drift (strain selection) Synthetic Genomics: Preparedness