EXTRAMURAL COMPUTATIONAL BIOLOGY AT NIH

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EXTRAMURAL COMPUTATIONAL BIOLOGY AT NIH

• Eric Jakobsson
• Chair, NIH Bioinformation Science and Technology
  Initiative Consortium
• Director, NIGMS Center for Bioinformatics and
  Computational Biology
• For CASC
• March 23, 2005

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Why Computational Biology at the NIH

• Because computation and information technology is
  an invaluable tool for understanding biological
  complexity, which is at the heart of advance in
  biomedical knowledge and medical practice.
• You cant translate what you dont
  understand---Elias Zerhouni, Director of the
  National Institutes of Health, commenting on the
  relationship between basic research and
  translational research, that transforms the
  results of basic research into a foundation for
  clinical research and medical practice.

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Some important problems with biomedical computing
tools are

• They are difficult to use.
• They are fragile.
• They lack interoperability of different
  components
• They suffer limitations on dissemination
• They often work in one program/one function mode
  as opposed to being part of an integrated
  computational environment.
• There are not sufficient personnel to meet the
  needs for creating better biological computing
  tools and user environments.

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Why the problems with biological computing tools
must be fixed. I. Computation is at the heart of
todays leading edge biomedical science, for
example

• X-ray structure of biomoleculesrequires
  sophisticated computation for image
  reconstruction for diffraction data.
• Discovery of new genesThe experimental work
  requires augmentation by bioinformatics for
  identification of genes by sequence analysis.
• Magnetic resonance imagingRequires sophisticated
  mathematical and computational techniques for
  inferring structure and image from nmr spectra.

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Why the problems with biological computing tools
must be fixed II. Computation holds great promise
for future progress in biomedical science

• Cataloguing and analyzing individual genome-based
  variations to permit customized diagnosis and
  therapy.
• Building comprehensive pathway models for human
  and pathogen cells to provide a framework for
  understanding normal function and disease at the
  subcellular level.
• Building and deploying dynamic models of disease
  epidemics as a tool for responding to natural
  pandemics and bioterrorist attacks
• Use of biomimetic principles to construct
  Computer Aided Design systems for molecular
  devices

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The Paradox of Computational Biology--Its
successes are the flip side of its deficiencies.

• The success of computational biology is shown by
  the fact that computation has become integral and
  critical to modern biomedical research.
• Because computation is integral to biomedical
  research, its deficiencies have become
  significant rate limiting factors in the rate of
  progress of biomedical research.

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Mission Statement

• In ten years, we want every person involved in
  the biomedical enterprise---basic researcher,
  clinical researcher, practitioner, student,
  teacher, policy maker---to have at their
  fingertips through their keyboard instant access
  to all the data sources, analysis tools, modeling
  tools, visualization tools, and interpretative
  materials necessary to do their jobs with no
  inefficiencies in computation or information
  technology being a rate-limiting step.
• In twenty years, we want intelligent
  computational agents to do complex query and
  modeling tasks in the biomedical computing
  environment, freeing humans for creative
  hypothesis construction and high level analysis
  and interpretation.

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Historical Highlights

• 1999Botstein-Smarr Committee Recommends
  Establishment of BISTI and of national biomedical
  computing centers.
• 2001BISTI establishedsearch for Chair launched
• 2003Chair hired, Funding Announcement Issued for
  National Centers for Biomedical Computing,
  Digital Biology Week is held in Collaboration
  with NSF and NIST

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In 2004

• First Set of National Centers for Biomedical
  Computing is established
• Funding Announcement will be issued for smaller
  projects to collaborate with the centers in
  creating the national biomedical computing
  infrastructure.

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In 2005

• Establish second set of National Centers for
  Biomedical Computing
• Establish first set of collaborating projects
  with the National Centers for Biomedical
  Computing.
• Ramp up to full functionality oversight and
  coordination of the national network of
  collaborating projects to create the National
  Program of Excellence in Biomedical Computing for
  the creation of a excellent national biomedical
  computing environment.
• Expand coordinated efforts with other agencies
  where there is synergy. (Currently NSF-NIH
  Biology-Mathematics Initiative is in its third
  year, multi-agency multiscale modeling initiative
  is in its first year, formal and informal
  planning meetings are underway with other
  agencies.)

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What also happened in 2003-2005

• Significant other compute-intensive biology
  initiatives got launched around the NIH and in
  other agencies (for example multi-scale
  biological modeling jointly with
  NIH/NSF/DOE/NASA, other roadmap initiatives,
  systems biology, clinical informatics, etc.)
• We didnt worry much about overlap and synergy
  going into this period because the gaps were so
  great.

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The next stage

• We are creating a coordinating group whose
  ongoing mission will be to monitor the various
  compute-intensive activities supported by NIH to
• Eliminate gaps
• Minimize overlap
• Identify and exploit synergies.

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We want to work with computer scientists

• To identify areas of computer science that are
  likely to be particularly important for
  biomedical research, and should therefore be
  supported by NIH, just as we support areas of
  basic biological science that are important for
  biomedicine.

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II. We want you if.

• You have ideas that can contribute to realizing
  the NIH vision.
• You have the skills and motivation to implement
  those ideas.
• The right vehicle for realizing your ideas is
  EITHER a large project or a small project.

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Looking at the NIH for support for computational
projects I General Issues

• First Principle NIH is a mission-driven agency.
  We support basic science (lots of it) and
  technology and infrastructure development (on an
  increasing trend line), but it all must be
  justifiable by a payoff down the line in
  improving the health of the American people.
• Corollary Principle We understand that the
  payoff may not be immediate, so we support work
  where the payoff is a decade or more in the
  future. It is better to present a justification
  for a reasonable but long-term payoff than an
  unrealistic short-term payoff.

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Looking at the NIH for support for Computational
Projects II Perspectives on the Role of
Computation in Biomedical Research and Health
Care Delivery

• We see that non-trivial computation is critical
  to every aspect of our mission, from the most
  basic research to the efficient and effective
  delivery of health care in all venues.
• We see the corollary Inefficiencies, gaps, and
  flaws in computation are limiting the pace and
  scope of all aspects of our mission.
• We have only gotten the message recently, so we
  are a work-in-progress with respect to
  implementing our understandings about computation
  in programs and practices.
• We need computer scientists, computational
  scientists, and information technologists to be
  partners with NIH in getting it right.

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Looking at the NIH for support for computational
projects III Finding out what NIH actually funds

• CRISP data base (Google NIH CRISP provides
  keyword-searchable database of all NIH-funded
  projects from 1972-2004
• Comprehensive access to publications by NIH
  grantees provided by author-searchable Pubmed
  literature database (Google pubmed)

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Looking at the NIH for support for computational
projects IV Building on your knowledge of what
we now do to what we might support you for doing

• First-stop (but not one stop) information
  source is the BISTI home page (Google NIH
  BISTI), button under Funding
• If you dont find a funding announcement that
  fits your ideas/capabilities, but you feel you
  have something to contribute, dont hesitate to
  send an unsolicited application. (Receipt dates
  February 1, June 1, and October 1 each year for
  new applications). Success rates for unsolicited
  applications are often as good as, in some cases
  better than, success rates for proposals
  submitted in response to specific funding
  announcements.
• Consult with an NIH Program Director at the
  concept development stage. This is easy if you
  are responding to a funding announcementthe
  right contact information is in the funding
  announcement. For an unsolicited application,
  you may need to browse through Web sites for many
  of the semi-autonomous 27 Institutes and Centers
  that comprise the NIH, as well as the NIH Roadmap
  site, that contains information on NIH-wide
  initiatives. But---NIH is a strongly
  interconnected community, so if you start calling
  program staff and the first person you call is
  not the right person, you will get good direction
  to the right person fairly quickly.

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Looking at the NIH for support for computational
projects IV Building on your knowledge of what
we now do to what we might support you for doing
(continued)

• Research study sections as well as programs
  (Google NIH CSR), button under Study Section
  Information.
• On study section targeting, consult with Program
  Director and/or Scientific Review Administrator
  (Understand that program and review functions at
  NIH collaborate with each other but are
  independently accountable. This is different
  from NSF, where the same individuals are
  responsible for both creating program and
  overseeing review. With respect to NIH review
  issues, the AUTHORITATIVE information comes from
  the review side)
• FOLLOW THE RULES AND GUIDELINES! (Google NIH
  398 in addition to particular funding
  announcements.) That gives program and review
  staff more time to deal with your scientifically
  substantive concerns, because they wont have to
  work around emergent procedural issues.

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Looking at the NIH for support for computational
projects IV Building on your knowledge of what
we now do to what we might support you for doing
(final)

• Develop an NIH grant journal club (or
  comparable structure) at your institution where
  colleagues read and critique each others NIH
  grant applications and progress reports in
  preparation.

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THE BEGINNINGThank you for your attention and
your commitment to building the future