The National Human Genome Research Institute (NHGRI) has been guided, since the inception of the Human Genome Project in 1990, by a sequential series of plans, each of which has been developed with considerable input from the scientific community. These plans have always laid out ambitious goals and measurable objectives to gauge progress. NHGRI initiated its most recent planning process in 2008 and concluded with the publication in February 2011 of its newest strategic plan, Charting a Course for Genomic Medicine from Base Pairs to Bedside (Nature, 10 February 2011; Volume 470). The
phenomenal advances that have marked genomics and have allowed genomic applications to transform many important fields made it an opportune time for the Institute to take a new look at genomics and its future.
The purpose of this document is to provide information to investigators about the breadth of research falling within NHGRI’s mission. When appropriate, NHGRI will publish Requests for Applications that will be used to stimulate research in specific areas, to fill gaps in research knowledge, or to generate community resources that will further the mission of genomics or ELSI research.
The following are areas of high program relevance for investigator-initiated applications; they are not listed in priority order.
Technology and Methods Development
Technology development in DNA sequencing and genotyping are examples of activities that have changed the nature of what scientific research questions are practical to address, have enabled new approaches, and have facilitated the development of new community resource data sets. Many areas of critical importance to the realization of the genomics-based vision for biomedical research require
continued technological and methodological developments before pilots and then large-scale approaches can be attempted. Accordingly, the NHGRI will continue to support the development of new, fundamental technologies in all areas of genomics. Important areas in which technology development applications would be responsive to this Program Announcement include (but are not limited to) analyses of gene expression and other molecular phenotypes, discovery and characterization of genetic variation; identification of the genetic contributions to health, disease, and drug response; statistical analytic methods for understanding human genomic variation and its relationship to health and disease; and chemical genomics. There is also continued need to support technology development for the
comprehensive discovery of functional elements in the human and model organism genomes, and new DNA sequencing technology. Many of these assays would benefit from the ability to work with very small amounts of starting material, to the limit of single cells, along with minimally-invasive human specimens that are easy to collect, handle, and store. As these technologies mature, emphasis should be on high throughput, cost-effective methods that consistently produce very high quality data.
The Institute also places high priority on contributing selectively to the development of new and needed technology in related areas, such as proteomics and systems biology research, when NHGRI funding can be used to further a truly unique development that will have a significant impact on the field.
Bioinformatics and Computational Biology
The development of new sequencing technologies has dramatically increased the amount of data produced for genomics. NHGRI encourages new computational applications for the production,
processing, secure sharing, and analysis of data from these new sequencing platforms. The NHGRI has also supported the generation of many other large-scale genomic data sets such as haplotype maps, genetic variants, transcriptome measurements, functional elements, and protein interactions,. NHGRI also encourages the development of new computational methods and tools to enable the analysis of these and other large datasets, and to extract useful biological information from them. These applications would include better computational methods for storage, access, compression and transfer of large genomic
NIH, CDC, FDA, and ACF Program Descriptions and Research Topics NHGRI 110 datasets by biomedical researchers along with better analysis methods to interpret these data and integrate them with other data types. Methods that are fast and computationally efficient are highly desirable.
Where possible, existing community data standards and methods for data exchange should be used in the development of these new methods and tools. Further information on programs related to genomic databases and computational biology is available at this web site: http://www.genome.gov/10001735. Genomic databases are essential resources for the biological and biomedical research communities. The creation and maintenance of effective databases are as important a component of research funding as is data generation. NHGRI has been a primary source of support for several major genetics/genomics- oriented databases and will continue to foster technology improvements to develop effective methods for integrating, displaying, and providing access to genomic information. Projects developing new database and data science technologies to improve the utility of genome information would be appropriate as applications
Some genomic data analysis and display tools have been developed that already are used in the
community that would benefit from additional work to support broader dissemination, for example making them efficient, reliable, robust, well-documented, and well-supported. NHGRI will support projects to extend the support for these informatics tools to make them readily adopted by any biomedical research laboratory that wishes to use genomic technologies to address biological questions.
Population Genomics and Genomic Medicine
Population genomics applies genomic technologies, such as genome-wide association testing and sequencing, to population studies to identify genes or variants that affect common etiologically complex conditions and predict individual risk. Genomic medicine is an emerging discipline that investigates the value of applying genomic methods in clinical care for the diagnosis, treatment, and prevention of complex diseases. The research scope of Population Genomics and Genomic Medicine at NHGRI includes: developing resources and statistical methods for observational studies and clinical trials incorporating advanced genomic technologies; conducting proof-of-principle studies that apply genomic technologies to epidemiologic and clinical research; developing research methods and infrastructure needed for future epidemiologic and clinical studies of genetic and environmental contribution to disease; assessing phenotypic manifestations of genetic variants through electronic medical records (EMRs); integrating genomic results and clinical decision support into EMRs, and assessing the impact of genetic information on health outcomes and delivery of care. For additional information about Genomic Medicine NHGRI, please visit this web site: http://www.genome.gov/27550079.
Ethical, Legal and Social Implications
NHGRI, through the ELSI Research Program, supports research studies that examine issues and, where appropriate, develop policy options regarding the ethical, legal and social implications of genomics. These studies may focus on issues associated with genomic research, genomic medicine or broader societal effects of genomic information and technologies. More detailed information on specific ELSI research priorities within each of these broad areas is available on the ELSI Research priorities web
site: http://www.genome.gov/27543732.
Other Research Topics Within the Mission of the Institute
Individuals interested in any of the above listed areas are encouraged to contact the NHGRI staff listed below. For more specific information about areas relevant to NHGRI’s mission, please visit our home page at http://www.genome.gov/Grants/
NIH, CDC, FDA, and ACF Program Descriptions and Research Topics NIMH 111