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“Secrecy is a!
Public Health Problem”!
         Jonathan G. Izant
        Sage Bionetworks
   www.sagebase.org @SageBio
     AAAS 18 February 2012
denial
What is the real problem?
•    Profit margin too low?
•    No one willing to pay?
•    No one able to pay?
•    Internal research costs too high?
•    Low hanging fruit picked?
•    Genome has not delivered?
•    Companies can’t execute on strategy?
•    Regulatory hurdles too high?
•    Clinical trials too difficult and expensive?

In fact, all are true but none is the real problem
the real problem

•  We need to rebuild the drug discovery
   process so that we better understand
   disease biology

•  We need to reshape the way researchers,
   citizens, companies and funders interact
genetic regulation circa 1970
Genetic networks
The opportunity

•  Stunning technologies are generating heaps of
   genomic and clinical data

•  Bionetworks using integrative genomic approaches
   can highlight the non-redundant components-
   can find drivers of the disease and of therapies

•  Need to develop ways to host massive amounts of
   data, evolving representations of disease as
   represented by these probabilistic causal disease
   models
Network biology collaborations involve multiple
specialized labs, big data, sophisticated methods and
the results are often published in open access journals
Collaboration
    -  Multiple labs; specialized;
    -  Biologists, clinicians,
       statisticians, engineers, etc
Technology
    - Sophisticated technologies
Data
    -    >5x108 data points

Methods
    -  Computationally intensive
       (5000 node cluster)

Publish
    -    Open access journal
    -    18 figures, 19 tables
    -    Gigabytes of data
Catalytic nonprofit formed in 2009

Vision: to create a “Commons” where
 integrative bionetworks are evolved
by contributor scientists with a shared
vision to accelerate the elimination of
            human disease
Principles
Understanding human biology requires a new community-based vision of open access innovation that
   respects and links all stakeholders and supports a new culture of cooperative, data-intensive science.

We pledge to take up this challenge and have drafted the Sage Bionetworks Commons Principles to guide
   the development of an open source community where computational biologists can develop and test
   competing models built from common resources.

1.  The purpose of the Commons is to expedite            the pathway to knowledge,
    treatment, and prevention of disease.
2.  We will promote collaborative discovery through the creation and support of a
    broadly accessible digital Commons consisting of curated data and methodological tools in
    which analytical results are shared in a transparent, open fashion.
3.  The Commons will respect the rights and interests of all contributors
    including individuals from whom data are derived, researchers who collect and analyze data,
    and scientists and physicians who develop and implement healthcare advances. Those not
    respecting these rights will be excluded from the Commons.
4.  Contributions to the Commons shall be appropriately acknowledged and
    attributed.
5.  The Commons will promote data and tool sharing and distribution using standards that
    enable efficient reuse, compilation and comparison.
6.  The Commons will hold no intellectual property rights in, and will not permit
    encumbrances on, data and other elements within the Commons. This will not, however,
    preclude individuals from protecting new goods and services developed using data and other
    elements from the Commons.
What is Sage Bionetworks? - People
                                           •  Stephen Friend, MD, PhD
                                           •  Jonathan Derry, PhD                  >20 research scientists with
      Rosetta                              •  Adam Margolin, PhD
                                                                                      PhDs/MDs.
                                           •  Jonathan Izant, PhD
   Inpharmatics,                           •  Solly Sieberts, PhD
                                           •  Xia Yang, PhD                        537 peer-reviewed scientific
    Merck & Co                             •  Eric Huang, MD PhD
                                                                                       publications.
                                           •  Christine Suver, PhD
    University of Washington




                                                                        Research
                                           •  Thea Norman, PhD
          Duke University                  •  Zhi Wang, PhD                        385 combined years of
                                           •  Chris Gaiteri, PhD                       biomedical research
  Broad Institute of MIT and Harvard       •  Charles Ferte, MD PhD
                                           •  Elias Neto, PhD
                                                                                       experience in academia and
       B&M Gates Foundation                                                            industry.
                                           •  Lara Mangravite, PhD
           Jackson Labs                    •  Justin Guinney, PhD
                                           •  Qingying Meng, PhD                   7 software engineers.




                                                                        ------
  University of California Davis           •  Mette Peters, PhD
      University of Michigan               •  Vitalina Komashko, PhD
                                           •  Brig Mecham, PhD                      90 years of industry
               Ambryx                      •  Andrew Twister, MD PhD                 experience: Deployment of




                                                                        Software
     University of Pittsburgh              •  Matt Furia                             professional software
                                           •  Brian Bot                              applications to over 100
             Mayo Clinic                   •  In Sock Jang, PhD
                                                                                     million users.
     University of Wisconsin
                                           • Mike Kellen, PhD
Children’s Hospital of Oakland Institute   • Nicole Deflaux, PhD                    5,000 node in-house
                                           • Bruce Hoff, PhD
        Columbia University                                                          supercomputer cluster, and
                                           • Dave Burdick
                                           • John Hill                               tight integration with cloud-
     Institute for Systems Biology
                                           • Xa Schildwachter                        compute vendors.
              Teranode                     • Brian Holt
               Amazon
What is Sage Bionetworks? - Partners

Funders &
Nonprofits



 Pharma
  & IT



Research
Partners
Synapse
Sage Synapse : Contribute to the Cure                                                                                                                                                          http://synapse.sagebase.org/
                                                                                                                                                                                                                               •  Open computational resource offering network
                                                                                                                                                                                                                                  models of disease and the underlying datasets
                                                                                                                                                                                     REGISTER        LOGIN
                                                                                                                                                                                                                                  and algorithms used to construct them.
                WELCOME TO SYNAPSE
                Synapse is an online community built for a new biology... more open, more collaborative, more data-driven, and more reproducible.                                                                              •  Synapse integrates a data and network
                                                                                                                                                                                                                                  repository, the IT infrastructure in which the data
                                                                                                                                                                                                                                  are housed and the tools that allow manipulation
                     Everything                                                                                                                                                                 SEARCH




                Development Update
                Synapse is currently in Alpha development. This prototype has been developed to
                demonstrate our vision for the technology and solicit feedback from the community.
                The ability to create accounts and download Sage-hosted data is operational now.
                                                                                                                 Call for ALPHA USERS
                                                                                                                 Are you interested in working with Sage to start a pilot project on Synapse? Please let
                                                                                                                 us know at synapseInfo@sagebase.org
                                                                                                                                                                                                                                  and analysis.
                Some of the other functionality of the site is still under development.                                                                                              CREATE AN ACCOUNT




                Projects in the
                Spotlight
                                                                     FEDERATION AGING                                    SAGEBIOCURATION                                     START YOUR OWN
                                                                                                                                                                                                                               •  Synapse is an innovation space where
                                                                                                                                                                                                                                  researchers can compute and collaborate on
                Project spotlight description...                   PROJECT                                                                                                 PROJECT!
                                                                                                                    The Sage Bio Curation project is an
                                                                   The Federation Aging project is                  umbrella for all Sage Bionetworks-                     Get started using Synapse today by
                                                                   exploring the large effect of age on             curated projects.                                      creating your own Project.
                                  START A PROJECT
                                                                   human gene expression by




                                                                                                                                                                                                                                  genomic datasets, use tools to build models of
                                                                   exploring a set of genes whose
                                                                   expression levels are tightly
                                                                   associated with age.




                Synapse News                                                                                     Top Synapse Contributors
                                                                                                                                                                                                                                  human disease, and modify those built by others.
                What's happening on Synapse                                                                      Synapse users who are actively contributing data


                      New Normalization Analysis                                                                               Charles Sawyers et al, MSKCC



                                                                                                                                                                                                                               •  Contributors are active participants that build
                12-Apr-2011: A new analysis method for             Schadt's New Diabetes Model                                 DNA copy number, mRNA expression profiles, candidate gene resequencing, and
                normalizing data was published by Brig          08-Apr-2011: Eric Schadt and colleagues                        clinical traits from 218 prostate tumors.
                Mecham.                                         have published an article on a new model for
                                                                diabetes.                                                      Amanda Myers, University of Miami



                                                                                                                                                                                                                                  collective content in effect ‘crowdsourcing’ the
                                                                                                                               Genotypes, mRNA expression profiles, and clinical traits from 176 Alzheimer
                                                                                                                               disease and 188 non-diseased brain samples.


                                                                                                                               Beatriz Carvalho & Gerrit Meijer, VUMC



                                                                                                                                                                                                                                  evolution of disease models creating an
                                                                                                                               DNA copy number, mRNA expression, and tumor traits from 36 colorectal
                                                                                                                               adenocarcinoma and 33 adenoma tumors.


                                                                                                                 See all contributors...




                WITH SUPPORT                                                                                                                                FOLLOW                    CONTACT INFO
                                                                                                                                                                                                                                  accelerated mechanism for the dissemination of
                                                                                                                                                                                                                                  knowledge.
                FROM                                                                                                                                        US ON                     Sage Bionetworks
                                                                                                                                                                                      1100 Fairview Ave N
                                                                                                                                                                                      Seattle, WA 98109
                                                                                                                                                                                      synapseInfo@sagebase.org




                Copyright 2011 Sage Bionetworks                                                         Home / Privacy Policy / Platform support / Creative Commons License / FAQ / Submit feedback




1 of 1                                                                                                                                                                                                           2/16/12 1:26 PM
“WE CONSENT”
  Portable Legal Consents
Compliant and standardized
  tool for engaging with
  and empowering citizens
  and patients
Jonathan Izant AAAS Annual Meeting 2012-02-18
Clinical Trial Comparator Arm
           Partnership (CTCAP)

  Description: Collate, Annotate, Curate and Host Clinical
   Trial Data with Genomic Information from the Comparator
   Arms of Industry and Foundation Sponsored Clinical Trials:
   Building a Site for Sharing Data and Models to evolve
   better Disease Maps.
  Public-Private Partnership of leading pharmaceutical
   companies, clinical trial groups and researchers.
  Neutral Conveners: Sage Bionetworks and Genetic
   Alliance [nonprofits].
  Initiative to share existing trial data (molecular and
   clinical) from non-proprietary comparator and placebo
   arms to create powerful new tool for drug development.
                   Started Sept 2010

                                                                16
The Federation Experiment
       Stephen Friend
      Sage Bionetworks

                         Andrea Califano
                          Columbia U.

Gary Nolan                Eric Schadt
 Stanford                 Mount Sinai


     Trey Ideker
       UCSD
Jonathan Izant AAAS Annual Meeting 2012-02-18
Jonathan Izant AAAS Annual Meeting 2012-02-18
Lessons

  •  Building transformative technology
     is (relatively) easy

  •  Transforming people is hard
Why is it so hard to share data?
Traitwise Survey Congress Participants
Biomedical research lives in a cottage
industry tradition
Academic researchers live in a complex
professional ecosystem
“Secrecy is a!
Public Health Problem”!
“If you move the food bowl
   the cats will follow”!
                       -Sharon Terry!




         Sage Bionetworks
    www.sagebase.org @SageBio

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Jonathan Izant AAAS Annual Meeting 2012-02-18

  • 1. “Secrecy is a! Public Health Problem”! Jonathan G. Izant Sage Bionetworks www.sagebase.org @SageBio AAAS 18 February 2012
  • 3. What is the real problem? •  Profit margin too low? •  No one willing to pay? •  No one able to pay? •  Internal research costs too high? •  Low hanging fruit picked? •  Genome has not delivered? •  Companies can’t execute on strategy? •  Regulatory hurdles too high? •  Clinical trials too difficult and expensive? In fact, all are true but none is the real problem
  • 4. the real problem •  We need to rebuild the drug discovery process so that we better understand disease biology •  We need to reshape the way researchers, citizens, companies and funders interact
  • 7. The opportunity •  Stunning technologies are generating heaps of genomic and clinical data •  Bionetworks using integrative genomic approaches can highlight the non-redundant components- can find drivers of the disease and of therapies •  Need to develop ways to host massive amounts of data, evolving representations of disease as represented by these probabilistic causal disease models
  • 8. Network biology collaborations involve multiple specialized labs, big data, sophisticated methods and the results are often published in open access journals Collaboration -  Multiple labs; specialized; -  Biologists, clinicians, statisticians, engineers, etc Technology - Sophisticated technologies Data -  >5x108 data points Methods -  Computationally intensive (5000 node cluster) Publish -  Open access journal -  18 figures, 19 tables -  Gigabytes of data
  • 9. Catalytic nonprofit formed in 2009 Vision: to create a “Commons” where integrative bionetworks are evolved by contributor scientists with a shared vision to accelerate the elimination of human disease
  • 10. Principles Understanding human biology requires a new community-based vision of open access innovation that respects and links all stakeholders and supports a new culture of cooperative, data-intensive science. We pledge to take up this challenge and have drafted the Sage Bionetworks Commons Principles to guide the development of an open source community where computational biologists can develop and test competing models built from common resources. 1.  The purpose of the Commons is to expedite the pathway to knowledge, treatment, and prevention of disease. 2.  We will promote collaborative discovery through the creation and support of a broadly accessible digital Commons consisting of curated data and methodological tools in which analytical results are shared in a transparent, open fashion. 3.  The Commons will respect the rights and interests of all contributors including individuals from whom data are derived, researchers who collect and analyze data, and scientists and physicians who develop and implement healthcare advances. Those not respecting these rights will be excluded from the Commons. 4.  Contributions to the Commons shall be appropriately acknowledged and attributed. 5.  The Commons will promote data and tool sharing and distribution using standards that enable efficient reuse, compilation and comparison. 6.  The Commons will hold no intellectual property rights in, and will not permit encumbrances on, data and other elements within the Commons. This will not, however, preclude individuals from protecting new goods and services developed using data and other elements from the Commons.
  • 11. What is Sage Bionetworks? - People •  Stephen Friend, MD, PhD •  Jonathan Derry, PhD >20 research scientists with Rosetta •  Adam Margolin, PhD PhDs/MDs. •  Jonathan Izant, PhD Inpharmatics, •  Solly Sieberts, PhD •  Xia Yang, PhD 537 peer-reviewed scientific Merck & Co •  Eric Huang, MD PhD publications. •  Christine Suver, PhD University of Washington Research •  Thea Norman, PhD Duke University •  Zhi Wang, PhD 385 combined years of •  Chris Gaiteri, PhD biomedical research Broad Institute of MIT and Harvard •  Charles Ferte, MD PhD •  Elias Neto, PhD experience in academia and B&M Gates Foundation industry. •  Lara Mangravite, PhD Jackson Labs •  Justin Guinney, PhD •  Qingying Meng, PhD 7 software engineers. ------ University of California Davis •  Mette Peters, PhD University of Michigan •  Vitalina Komashko, PhD •  Brig Mecham, PhD 90 years of industry Ambryx •  Andrew Twister, MD PhD experience: Deployment of Software University of Pittsburgh •  Matt Furia professional software •  Brian Bot applications to over 100 Mayo Clinic •  In Sock Jang, PhD million users. University of Wisconsin • Mike Kellen, PhD Children’s Hospital of Oakland Institute • Nicole Deflaux, PhD 5,000 node in-house • Bruce Hoff, PhD Columbia University supercomputer cluster, and • Dave Burdick • John Hill tight integration with cloud- Institute for Systems Biology • Xa Schildwachter compute vendors. Teranode • Brian Holt Amazon
  • 12. What is Sage Bionetworks? - Partners Funders & Nonprofits Pharma & IT Research Partners
  • 13. Synapse Sage Synapse : Contribute to the Cure http://synapse.sagebase.org/ •  Open computational resource offering network models of disease and the underlying datasets REGISTER LOGIN and algorithms used to construct them. WELCOME TO SYNAPSE Synapse is an online community built for a new biology... more open, more collaborative, more data-driven, and more reproducible. •  Synapse integrates a data and network repository, the IT infrastructure in which the data are housed and the tools that allow manipulation Everything SEARCH Development Update Synapse is currently in Alpha development. This prototype has been developed to demonstrate our vision for the technology and solicit feedback from the community. The ability to create accounts and download Sage-hosted data is operational now. Call for ALPHA USERS Are you interested in working with Sage to start a pilot project on Synapse? Please let us know at synapseInfo@sagebase.org and analysis. Some of the other functionality of the site is still under development. CREATE AN ACCOUNT Projects in the Spotlight FEDERATION AGING SAGEBIOCURATION START YOUR OWN •  Synapse is an innovation space where researchers can compute and collaborate on Project spotlight description... PROJECT PROJECT! The Sage Bio Curation project is an The Federation Aging project is umbrella for all Sage Bionetworks- Get started using Synapse today by exploring the large effect of age on curated projects. creating your own Project. START A PROJECT human gene expression by genomic datasets, use tools to build models of exploring a set of genes whose expression levels are tightly associated with age. Synapse News Top Synapse Contributors human disease, and modify those built by others. What's happening on Synapse Synapse users who are actively contributing data New Normalization Analysis Charles Sawyers et al, MSKCC •  Contributors are active participants that build 12-Apr-2011: A new analysis method for Schadt's New Diabetes Model DNA copy number, mRNA expression profiles, candidate gene resequencing, and normalizing data was published by Brig 08-Apr-2011: Eric Schadt and colleagues clinical traits from 218 prostate tumors. Mecham. have published an article on a new model for diabetes. Amanda Myers, University of Miami collective content in effect ‘crowdsourcing’ the Genotypes, mRNA expression profiles, and clinical traits from 176 Alzheimer disease and 188 non-diseased brain samples. Beatriz Carvalho & Gerrit Meijer, VUMC evolution of disease models creating an DNA copy number, mRNA expression, and tumor traits from 36 colorectal adenocarcinoma and 33 adenoma tumors. See all contributors... WITH SUPPORT FOLLOW CONTACT INFO accelerated mechanism for the dissemination of knowledge. FROM US ON Sage Bionetworks 1100 Fairview Ave N Seattle, WA 98109 synapseInfo@sagebase.org Copyright 2011 Sage Bionetworks Home / Privacy Policy / Platform support / Creative Commons License / FAQ / Submit feedback 1 of 1 2/16/12 1:26 PM
  • 14. “WE CONSENT” Portable Legal Consents Compliant and standardized tool for engaging with and empowering citizens and patients
  • 16. Clinical Trial Comparator Arm Partnership (CTCAP)   Description: Collate, Annotate, Curate and Host Clinical Trial Data with Genomic Information from the Comparator Arms of Industry and Foundation Sponsored Clinical Trials: Building a Site for Sharing Data and Models to evolve better Disease Maps.   Public-Private Partnership of leading pharmaceutical companies, clinical trial groups and researchers.   Neutral Conveners: Sage Bionetworks and Genetic Alliance [nonprofits].   Initiative to share existing trial data (molecular and clinical) from non-proprietary comparator and placebo arms to create powerful new tool for drug development. Started Sept 2010 16
  • 17. The Federation Experiment Stephen Friend Sage Bionetworks Andrea Califano Columbia U. Gary Nolan Eric Schadt Stanford Mount Sinai Trey Ideker UCSD
  • 20. Lessons •  Building transformative technology is (relatively) easy •  Transforming people is hard
  • 21. Why is it so hard to share data?
  • 23. Biomedical research lives in a cottage industry tradition
  • 24. Academic researchers live in a complex professional ecosystem
  • 25. “Secrecy is a! Public Health Problem”!
  • 26. “If you move the food bowl the cats will follow”! -Sharon Terry! Sage Bionetworks www.sagebase.org @SageBio