EXTRAMURAL COMPUTATIONAL BIOLOGY AT NIH

1. 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

2. 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 can�t translate what you don�t 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.

3. 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.

4. Why the problems with biological computing tools must be fixed. I. Computation is at the heart of today�s leading edge biomedical science, for example: X-ray structure of biomolecules�requires sophisticated computation for image reconstruction for diffraction data. Discovery of new genes�The experimental work requires augmentation by bioinformatics for identification of genes by sequence analysis. Magnetic resonance imaging�Requires sophisticated mathematical and computational techniques for inferring structure and image from nmr spectra.

5. 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

6. 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.

7. 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.

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

9. 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.

10. 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.)

11. 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 didn�t worry much about overlap and synergy going into this period because the gaps were so great.

12. 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.

13. 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.

14. 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.

15. 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.

16. 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.

17. 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�)

18. 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 don�t find a funding announcement that fits your ideas/capabilities, but you feel you have something to contribute, don�t 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 announcement�the 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.

19. 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 won�t have to work around emergent procedural issues.

20. 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 other�s NIH grant applications and progress reports in preparation.

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