The Centers of Excellence in Genomic Science (CEGS) program establishes academic Centers for advanced genome research at U.S. institutions. Each CEGS award supports a multi-investigator, interdisciplinary team to develop transformative genomic approaches to address a biomedical problem. A CEGS project will address a critical issue in genomic science, genomic medicine, or computational genomics, proposing a highly innovative solution that would be a major advance. The research will entail substantial risk, balanced by outstanding scientific and management plans and very high potential payoff. A CEGS will focus on the development of novel technological or computational methods for the production or analysis of comprehensive data sets, on a genome-scale biomedical problem, or on other ways to develop and use genomic approaches for understanding biological systems or furthering the application of genomic knowledge, data, and methods towards clinical applications. Each CEGS will nurture genomic science at its institution by facilitating the interaction of investigators from several disciplines. By training new and experienced investigators it will expand the pool of genomics scientists and engineers.
The goals of the Human Genome Project (HGP) were met with the completion of the mapping and sequencing of the human genome and the genomes of several important model organisms. The HGP and the related genomic research supported by NHGRI have been characterized by a focus on efficient data production; the development of new technologies; and large, comprehensive genomic data sets such as genomic maps and complete DNA sequences, human DNA sequence variation (the HapMap and 1000 Genomes Projects), and the functional elements of the human genome (ENCODE). Once the DNA sequence of an organism becomes available, many new avenues to study its biology are opened. However, new and improved concepts, research tools, methods, approaches, and capabilities are needed to discover and use the vast amount of biological information in complete genomic DNA sequences. Therefore, in 2000 NHGRI established the CEGS program (and NIMH joined in 2001) to stimulate the development of such new approaches, which involve computational, instrumental, biochemical, genetic, and analytical conceptual frameworks and technologies. Developing and implementing these approaches require the expertise of teams of investigators from several fields as well as substantial infrastructure. Some of the many important opportunities in genomics are described in “Charting a course for genomic medicine from base pairs to bedside” (Nature, 2011, 470:204-213) (http://www.genome.gov/27543215). Projects supported by the CEGS program are listed at http://www.genome.gov/10001771.
Scope of research
The purpose of the CEGS program is to support the development of highly innovative and transformative basic or clinically-oriented genomic approaches that open up ways to address important biomedical questions. The CEGS have explored ways to conduct biomedical research at a genomic scale and have developed new concepts, methods, approaches, tools, and technologies to allow novel analyses of biomedical questions from a genomic perspective. The resources needed to conduct the multi-faceted, multidisciplinary projects required to achieve substantial advances for these complex problems may be beyond the scope of an R01 award. Therefore, the CEGS program provides an opportunity to assemble the teams of investigators from diverse disciplines that will be required to approach biomedical problems using genomic tools in ways that otherwise are not possible. High priority will be given to projects that integrate multi-investigator, multi-disciplinary approaches to a focused scientific problem, including those that integrate one or more of computational, experimental, and clinical research approaches.
A CEGS will advance the state of the art in applying genomic approaches to biomedical studies by developing new genomic concepts, methods, technologies, or ways to analyze data, or by investigating novel ways to apply existing genomic-scale, comprehensive technologies to study a biological problem. It must be tightly focused on a single biomedical problem or on an approach to solving biomedical problems, using genomic concepts and methods.
The research plan for a CEGS must have a very high level of innovation. The product of CEGS research is expected to dramatically enhance the biomedical research community’s capabilities for conducting comprehensive, cost-effective, high-throughput biomedical studies related to the DNA sequence and sequence products, with a focus on human biology and disease. A CEGS application is expected to describe a specific and substantive approach, e.g., a concept, method, technology, or way to analyze data. A CEGS should take on the challenging aspects of a problem, including ones that have slowed progress in the research area. Other investigators might solve some of the problems on which a CEGS project has set its sights; a CEGS should be sufficiently nimble to be able to adopt those solutions, so that CEGS resources are applied toward tackling the unsolved challenges.
If the approach is likely to be developed by other projects over the same timeframe as the proposed CEGS, it is generally not appropriate for a CEGS. If a problem is well recognized in the field and multiple laboratories are working on solving it, then the project probably doesn’t meet the innovation standard required for a CEGS, although highly novel ways to solve the problem may be considered. Applications that use state-of-the-art science that fills in knowledge but does not break substantially new ground are not appropriate for this FOA; neither are applications that support research groups studying related problems but not focused on a specific coordinated approach.
Proposing to change the way genomic science will be done entails a substantial level of risk because the research will, by definition, not be incremental. To balance this risk, projects must include well-developed scientific and management plans to achieve a high pay-off result. Collaborations to develop genomic approaches require proficiency in several disciplines; a CEGS application should engage specialists in a wide range of fields such as biology, genetics, clinical medicine, physical sciences, statistics, mathematics, computer science, and engineering, as needed. The various activities of the program should be synergistic and interdependent, not simply related; each activity should produce results that are required for progress by the other activities.
This FOA does not list examples of possible CEGS themes because of the desire not to limit applicants’ imaginations and to encourage new ideas for genomic approaches to biological problems. Solving many important biomedical problems requires the collection and analysis of large data sets, such as many whole genomes, all expressed RNAs or proteins along with those genomes, entire gene families from many species, numerous gene regulatory or chromatin organizational elements for multiple cell states, or phenotypic data from many people. Therefore, the unifying theme for this program will be that the Centers will develop approaches to address important biomedical problems in a comprehensive manner and on a genomic scale. In this context, the term “genomics” is not limited to studies directly related to DNA sequence, but instead encompasses global, comprehensive, high-throughput, cost-effective approaches to studying biomedical systems, including, for example, DNA, RNA, and regulatory and biochemical pathways and networks. Some projects may result in new analyses of existing data sets, while others may result in technologies and methods that provide the ability to collect, analyze, and present new types of genomic data sets.
The genomic approaches and technologies that are developed should be applicable to a wide variety of cell types, organisms, or diseases, and should be usable in a global, high-throughput, cost-effective manner. Methods and concepts that are applicable only to a specific genetic locus, cell type, disease, or organ system will not be supported under this program. Model systems, such as one or a few gene families, regulatory networks, cell types, or diseases, may be used to develop the genomic approach, as long as the approach will be scalable and broadly applicable. To the extent that cost-effective, global approaches can be developed and also applied within the CEGS budget, such application of the new approach is acceptable. However, the budget limits under this FOA may preclude large-scale application of the genomic approach that is being developed.
The cost of collecting global data sets is often high; therefore, a CEGS application that aims to substantially reduce the cost of collecting a data set that currently can be collected only at great expense could be enabling to the genomics community, and is therefore considered appropriate for this FOA.
A CEGS may use large amounts of data to accomplish its goals. However, the application of genomic technologies for data production per se is not the purpose of a CEGS, and the CEGS program is not intended primarily to build infrastructure for the application of current genomic technologies. Applicants may use data sets collected under other funding, if the CEGS project’s purpose is to develop novel, integrated analyses that extend the interpretation and utility of those data. Decisions by NIH to embark on the large-scale implementation of any new tools developed by a CEGS to generate large data sets will require careful consideration, with advice from the scientific community.
Given all of these contingencies, potential applicants are strongly encouraged to contact NHGRI and NIMH staff early in the application development process. NHGRI will support work that uses any appropriate disease or model system that can be applied more generally; NIMH will support work that is related to mental illness or the brain.
Clinical trials (optional): CEGS applications may include activities that fit the clinical trials definition, such as testing whether new genomic assays or integration of genomic and clinical data improve a health outcome. The purpose of this FOA is to support the development of transformative genomic approaches, and is not intended to fund applications whose primary focus is on recruitment and data production for a clinical trial. The definition of clinical trials in NOT-OD-15-015 and https://grants.nih.gov/policy/clinical-trials/definition.htm is not intended to expand the scope of applications accepted by the CEGS program beyond studies that have a major genomic component and relate clearly to the aims of the program. Any applications including clinical trials are required to address the information listed for clinical trials. Applicants are strongly encouraged to discuss their research plans with NHGRI or NIMH program staff prior to submitting their applications.
Since the goal of the program is to stimulate rapid progress in genomics, it is expected that the results (e.g., publications, methods, data) will become available to the community throughout the duration of the award. Methods, data, and software developed under CEGS support should be released quickly in a way that provides broad access. See the Genomic Data Sharing policy at https://www.genome.gov/27562511/nhgri-implementation-of-nih-genomic-data-sharing-policy/ .
Preference will be given to the development of genomic methods for eukaryotes for which genome sequence and related data are already available. Methods development or pilot studies using other systems (e.g., eukaryotes whose genomes have not been sequenced, or prokaryotes whose genomic sequence is known) will be considered with adequate justification; the direct applicability of approaches developed in such a project to the analysis of eukaryotic genomes must be evident.
Where appropriate, integration with other NHGRI or NIH genomic initiatives (e.g., ENCODE (ENCyclopedia Of DNA Elements) [http://www.genome.gov/10005107], 1000 Genomes [http://www.genome.gov/27528684], GTEx (Genotype-Tissue Expression) [https://commonfund.nih.gov/GTEx], the Mammalian Gene Collection [http://mgc.nci.nih.gov], a Catalog of Published Genome-Wide Association Studies [http://www.genome.gov/26525384], ClinGen (Clinical Genome Resource) [https://www.genome.gov/27558993], or the PhenX Toolkit [http://www.genome.gov/27541903] will be considered advantageous.
For CEGS projects that raise substantial ethical, legal, or social issues (ELSI, e.g., the study of sequence variation in specific populations), the Center may include research that focuses on analysis of ELSI issues as they relate to the research proposed. To be considered for funding as part of the CEGS award, the ELSI research must be integrated with and highly relevant to the research plan. Information on the NHGRI ELSI research program is at http://www.genome.gov/10001618. Information on NHGRI’s Centers of Excellence in ELSI Research (CEERS) program is at http://www.genome.gov/15014773. A CEGS application that includes ELSI research should include ELSI scholars in the education and outreach activity. CEGS applications are not required to have an ELSI activity.
Genomics education and outreach activities
Each CEGS application is required to include an education and outreach activity that leverages the strengths of the Center and its investigators to further educate interdisciplinary scientists, including students and faculty, who will bring creativity to biomedical problems through a genomic approach. There is a shortage of investigators who have the interdisciplinary skills needed to conduct most effectively the types of genome-scale research, including concept and methods development, described in this FOA. One reason for this shortage is that there are too few environments in which there is active effort to disseminate knowledge of how genomic approaches can most effectively be incorporated into the design of basic and clinical biomedical research. The CEGS program is intended to help to alleviate this shortage by supporting the development of Centers that can serve as U.S. academic foci for genomics, beyond those previously developed by NHGRI (see e.g., http://www.genome.gov/10000950), and thereby to increase the cadre of investigators qualified to participate in the development and application of new genomic approaches to biomedical research.
To maximize the impact of these Centers, they should train new investigators and perform outreach to broaden the expertise of established investigators. This might, for example, include plans for investigators who are already accomplished in other fields of research and engineering to acquire expertise in genomics. Graduate students and postdoctoral fellows, at a minimum, should participate in the research; however, such participation alone will be considered insufficient to meet the educational and outreach goals of the CEGS program. Applicants are expected to develop creative approaches, complementing the standard training vehicles used by academic institutions (e.g., training grants, fellowships, research education programs, seminar programs, coursework). This education and outreach program should take advantage of unique aspects of the research program, the investigators’ talents, and other institutional resources to offer innovative, substantive opportunities for pre-doctoral students, post-doctoral fellows, and other investigators to develop expertise in genomics.
Participation of CEGS awardees in the Diversity Action Plan (DAP)
NHGRI strongly encourages CEGS awardees to participate in NHGRI’s DAP program, “Initiative to Maximize Research Education in Genomics: Diversity Action Plan (R25)” (https://grants.nih.gov/grants/guide/pa-files/PAR-16-345.html). The DAP application should be submitted only after a CEGS application has been identified for potential funding. Applicants are strongly encouraged to discuss the initial results of their CEGS applications with staff before applying for an R25.
Renewal grant applications are accepted in this program. Genomics is a rapidly changing field, and it is anticipated that most projects will likely have a limited time during which support as a CEGS will be appropriate, either because the project goals will have been accomplished or the Center will have developed to the point that support from another source will be more appropriate. Therefore, the total support for a CEGS award will be for a maximum of ten years: up to five years for the initial award, and then a renewal. Since a goal of this program is to build genomic capacity at various institutions, a CEGS PD/PI or research group may receive a maximum of ten years of support under this program.
The field of genomics continues to make remarkable advances over short periods of time. Projects seeking a renewal must propose to advance the state of the art of genomics and its applications to biomedicine substantially beyond what exists at the time of the renewal application, not only what existed at the time of the original application. It is not sufficient to maintain course if the state of the art has substantially advanced; for a renewal application, a Center that is merely meeting its originally-proposed goals would not be sufficient. Renewal applications, like new applications, should tackle the hardest problems in their area of focus, because those are the problems that are impeding progress in biomedical research. Successful renewals will also have established a track record in genomics education and outreach.
Deadlines: May 20, 2019; May 18, 2020; May 20, 2021 (letters of intent due sixty days prior to deadline)
Filed Under: Funding Opportunities