The NIH Bioinformatics and
Computational Biology
Peter Lyster PhD
Program Director, Computational Biology
and Bioinformatics
National Institute for Biomedical Imaging
and Bioengineering (NIBIB) at the
National Institutes of Health (NIH)
For the Coalition for Academic Scientific
Computation (CASC) Winter meeting,
February 4, 2004,Washington DC
User oriented 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.
Computational Biology at the NIH—
why, whence, what, whither
• Why—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.
Computational Biology at the NIH—
why, whence, what, whither
• Whence—Computation and information technology were
originally used as add-ons, to add value to experimental
and observational results that had sufficiently simple
patterns that they could be discerned by observation.
Often the computing technology was an almost invisible
partner to the experiments. For example, the 1951
Hodgkin-Huxley Nobel Prize work that elucidated the
bases of electrical excitability included calculations that
were done on an electromechanical calculator, and would
not have been feasible by hand or slide rule—yet it is not
often cited as an example of the importance of calculating
Computational Biology at the NIH—
why, whence, what, whither
• What—Today computation is at the heart of all leading
edge biomedical science. For leading examples, consider
this past year’s Nobel prizes:
• Structure of voltage-gated channels—required
sophisticated computation for image reconstruction for xray diffraction data, the mathematical techniques for which
were the subject of a previous Nobel prize.
• Discovery of water channels—The experimental work
required augmentation by bioinformatics for identification
of water channel genes by sequence homology.
• Magnetic resonance imaging—A large share of the prize
work was for the mathematical and computational
techniques for inferring structure and image from NMR
Computational Biology at the NIH—
why, whence, what, whither
Institutes and Centers at NIH support substantial
development and implementation of computation
and information technology embedded in
biomedical research.
Informatics is a key component of the NIH Roadmap
Roadmap Activities: Computation
– New Pathways to Discovery
• National Centers for Biomedical Computing
• Building Blocks, Biological Pathways, and
– Re-engineering the Clinical Research Enterprise
• National Electronic Clinical Trials and Research
Network (NECTAR)
• Dynamic Assessment of Patient-Reported Chronic
Disease Outcomes
Trans NIH Informatics Committee (TNIC)
Present State of Computational Biology
• Essentially all leading-edge biomedical research
utilizes significant computing.
• Development and initial implementation of
methods are largely the product of collaborations
with overlapping expertise---biologists who have
substantial expertise in computing with computer
scientists and other quantitative scientists who
have substantial knowledge of biology.
Computer scientists and other quantitative
scientists with little knowledge of biology are
generally unable to contribute to the
development of biomedical computing tools.
The Paradox of Computational Biology-Its successes are the flip side of its
• 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.
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.
Computational Biology at the NIH—why,
whence, what, whither
• Whither—The NIH Bioinformatics and Computational
Biology Roadmap:
• Was submitted to NIH Director Dr. Elias Zerhouni on May
28, 2003
• Is the outline of an 8-10 year plan to create an excellent
biomedical computing environment for the nation.
• Has as its explicit most ambitious goal “Deploy a rigorous
biomedical computing environment to analyze, model,
understand, and predict dynamic and complex biomedical
systems across scales and to integrate data and knowledge
at all levels of organization.”
1-3 year roadmap goals:
relatively low difficulty
1. Develop vocabularies, ontologies, and data schema for defined domains and
develop prototype databases based on those vocabularies, ontologies, and data
2. Require that NIH-supported software development be open source.
3. Require that data generated in NIH-supported projects be shared in a timely
4. Create a high-prestige grant award to encourage research in biomedical
5. Provide support for innovative curriculum development in biomedical
6. Support workshops to test different methods or algorithms to analyze the
same data or solve the same problem.
7. Identify existing best practice/gold standard bioinformatics and
computational biology products and projects that should be sustained and
8. Enhance training opportunities in bioinformatics and biomedical computing.
1-3 year roadmap goals:
moderate difficulty
• 1. Support Center infrastructure grants that include key building blocks
of the ultimate biomedical computing environment, such as:
integration of data and models across domains, scalability, algorithm
development and enhancement, incorporation of best software
engineering practices, usability for biology researchers and educators,
and integration of data, simulations, and validation.
• 2. Develop biomedical computing as a discipline at academic
• 3. Develop methods by which NIH sets priorities and funding options
for supporting and maintaining databases.
• 4. Develop a prototype high-throughput global search and analysis
system that integrates genomic and other biomedical databases.
4-7 year roadmap goals:
relatively low difficulty
• 1. Supplement existing national or regional highperformance computing facilities to enable biomedical
researchers to make optimal use of them.
• 2. Develop and make accessible databases based on
domain-specific vocabularies, ontologies, and data
• 3. Harden, build user interfaces for, and deploy on the
national grid, high-throughput global search and analysis
systems integrating genomic and other biomedical
4-7 year roadmap goals:
moderate difficulty
• 1. Develop robust computational tools and
methods for interoperation between biomedical
databases and tools across platforms and for
collection, modeling, and analyzing of data, and
for distributing models, data, and other
• 2. Rebuild languages and representations (such as
Systems Biology Markup Language) for higher
level function.
4-7 year roadmap goals: high
• 1. Ensure productive use of GRID computing
through participation of biologists to shape the
development of the GRID.
• 2. Develop user-friendly software for biologists to
benefit from appropriate applications that utilize
the GRID.
• 3. Integrate key building blocks into a framework
for the ultimate biomedical computing
8-10 year roadmap goals:
relatively low difficulty
• 1. Employ the skills of a new generation of
multi-disciplinary biomedical computing
8-10 year roadmap goals:
moderate difficulty
• Produce and disseminate professionalgrade, state-of-the art, interoperable
informatics and computational tools to
biomedical communities. As a corollary,
provide extensive training and feedback
opportunities in the use of the tools to the
members of those communities.
8-10 year roadmap goals: high
• Deploy a rigorous biomedical computing
environment to analyze, model, understand,
and predict dynamic and complex
biomedical systems across scales and to
integrate data and knowledge at all levels of
Initial Steps on the Roadmap
Plan I
• We have released a funding announcement, and
received proposals, for the creation of four NIH
National Centers for Biomedical Computing.
Each Center is to serve as the node of activity for
developing, curating, disseminating, and providing
relevant training for, computational tools and user
environments in an area of biomedical computing.
We hope ultimately to establish eight centers.
Initial Steps on the Roadmap
Plan II
• We are preparing a funding announcement
for investigator-initiated grants to
collaborate with the National Centers.
Instead of having big science and small
science compete with each other, we will
create an environment in which they will
work hand in hand for the benefit of all
Initial Steps on the Roadmap
Plan III
• We are preparing a funding announcement for
work on creating and disseminating curricular
materials that will embed the learning and use of
quantitative tools in undergraduate biology
education for future biomedical researchers. We
are committed to pressing a reform movement
in undergraduate biology education to ensure
an adequate number of quantitatively trained
and able biomedical researchers in the future.
Initial Steps on the Roadmap
Plan IV
• We are in the initial stages of establishing a formal
assessment and evaluation process. A possible
form is that an external group of scientists will
establish criteria by which to evaluate the
program, and a professional survey research group
will work with the scientists to implement the
ongoing assessment and evaluation plan, so that
prompt and appropriate mid-course corrections
and tuning will take place.
Key Features of the NIH Bioinformatics
and Computational Biology Roadmap
• Every component goes through NIH peer review system.
• Larger components are by cooperative agreement rather
than grant, with active continued participation by NIH
program staff.
• There is complete transparency about the rules and the
process (except for the confidentiality necessary for peer
• Assessment and Evaluation are built in from the start.
• Program, review, and evaluation are independent of each
expressed in the funding announcement for this project)
There is no prescribed single license for software produced in this project.
However NIH does have goals for software dissemination, and reviewers
will be instructed to evaluate the dissemination plan relative to these goals:
1) The software should be freely available to biomedical researchers and
educators in the non-profit sector, such as institutions of education,
research institutes, and government laboratories. 2) The terms of software
availability should permit the commercialization of enhanced or customized
versions of the software, or incorporation of the software or pieces of it into
other software packages. 3) The terms of software availability should
include the ability of researchers outside the center and its collaborating
projects to modify the source code and to share modifications with other
colleagues as well as with the center. A center should take responsibility
for creating the original and subsequent "official" versions of a piece of
software, and should provide a plan to manage the dissemination or
adoption of improvements or customizations of that software by others.
This plan should include a method to distribute other user's contributions
such as extensions, compatible modules, or plug-ins. The application
should include written statements from the officials of the applicant
institutions responsible for intellectual property issues, to the effect that the
institution supports and agrees to abide by the software dissemination
plans put forth in the proposal.
Possible areas of productive
interaction with other agencies
with DOE on microbial science and nanoscience and
with DARPA on microbial science and on nanoscience
and biotechnology
with USDA on nutrition and agricultural science
with NIST on data and software standards and on
with NSF on biology at all levels, on integrating
biomedical computational science with the
cyberinfrastructure initiative, on fostering
interdisciplinary collaborative science, on nanoscience,
and on biology education
with NASA and NOAA on environmental issues related
to health
National Institute for Biomedical
Imaging and Bioengineering
Dr. Roderic Pettigrew – Director
Improve health through fundamental discoveries,
design and development, and translation and
assessment of technological capabilities in
biomedical imaging and bioengineering, enabled
by relevant areas of information science, physics,
chemistry, mathematics, materials science, and
computer sciences.
NIBIB Computation Activities
• Biomedical Information Science and Technology
Consortium (BISTIC)
• Neuroinformatics
– Human Brain Project (HBP)
– Collaborative Research in Computational Neuroscience
– Neuroimaging Informatics Technology Initiative
• Interagency Modeling and Analysis Group
Interagency Modeling and Analysis Group
• Formed in 2003, lead by NIBIB
• Purpose: To promote modeling and
analysis methods in biomedical
• Interagency initiative on Multiscale
Interagency Modeling and Analysis Group
• Participants
• 13 NIH components (NIBIB, NIDA, NIGMS,
• 3 NSF directorates (ENG, CISE, and BIO)
NIBIB Program Areas
• Mathematical Models and
Computational Algorithms
• Bioinformatics and
Medical Informatics
• Human-Computer
Interface, Image Displays,
Perception, and Image
• Remote Diagnosis and
• Surgical Tools and
Imaging Device Development
Imaging Agent and Molecular
Probe Development
Tissue Engineering
Medical Devices and Implant
Therapeutic Agent Delivery
Systems and Devices
Biomechanics and Rehabilitation
Platform Technologies
Mathematical Models and
Computational Algorithms
• Multiscale, structural and functional modeling
• New, novel modeling methodology (nonlinear and
systems methods)
• Clinical decision algorithms
• Statistical methods and data reduction models
• Imaging algorithms (distortion correction and
motion detection)
• Data analysis methods
• Tangible molecular models
• Data acquisition, management and processing
• Data mining and data analysis
• Networked tools for transfer of images and radiological
reports (GRID)
• Digital atlases, gene expression maps, probabilistic maps
• Knowledge-based reporting systems
• Mapping and visualization of function and diseases
(genotype and phenotype)
• Medical informatics
• Biostatistics
Image Processing
• Segmentation and registration
• Image analysis, pattern recognition, computeraided diagnosis
• Multi-modal imaging analysis (PET, MR,…)
• Neuroimaging
• Mammography
• Perceptual modeling
• Dosage – Radiography
Remote Diagnosis and Therapy
Remote-monitoring and quantification of images
Data and model integration for critical care
Wearable sensors and data fusion
Haptics and tele-diagnostics
Neurophysiological interoperative monitoring
Internet-based home healthcare
Remote-management of disease
Surgical Tools and Techniques
• Computer-assisted surgery
• Simulated surgical training
• Image-guided interventions
Future Directions at NIBIB
– Interagency Modeling and Analysis
Group (IMAG)
– Systems Biology/Tissue Engineering
– Imaging Informatics
– Data Integration
– Large-scale Databases
NIBIB Program Contacts
Modeling / Bioinformatics / Neuroprosthesis / Telehealth Technologies
/ Biomechanics / Rehabilitation
Grace Peng – [email protected]
Biosensors / Tissue Engineering
Chris Kelley - [email protected]
Biomaterials / Nanotechnology
Peter Moy - [email protected]
Bioinformatics / Imaging Informatics
Peter Lyster - [email protected]
John Haller - [email protected]
Alan McLaughlin – [email protected]
Yantian Zhang – [email protected]
Meredith Temple-O’Connor - [email protected]

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