Frequently Asked Questions about the NHGRI Sequencing and Ethical, Legal, and Social Implications (ELSI) FOAs

National Human Genome Research Institute

National Institutes of Health
U.S. Department of Health and Human Services


Frequently Asked Questions about the NHGRI Sequencing and ELSI FOAs

Please Note: The announcement was published by the NCBI regarding the discontinuation of the Sequence Read Archive and Trace Archive repositories. This announcement does not alter the intent of the NHGRI to promote rapid release of prepublication sequencing data. Applicants should propose data release plans as guided by the FOAs.

New Presentation on the FOAs from the Information Session (1-31-2011) PDF file New
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Funding Opportunity Announcements (FOAs)

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Overview

Below is a list of Frequently Asked Questions and answers to those questions for the above FOAs, which are presented together because they represent a continuum of solicitations for two NHGRI programs: Large-scale Sequencing and Ethical Legal and Social Implications (ELSI). For any additional questions that are not addressed in the summary, please contact the program staff listed in the FOAs for which you plan to apply.

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General Questions

  1. If I apply to more than one of these FOAs, will that limit my chance of receiving any of these awards?

    You can apply to more than one of these FOAs. The same criteria will apply regardless of the number of FOAs to which you apply. Funding decisions will be based on the results of the review and program priority, whether or not you can devote enough time to each proposed project, and whether or not you have adequate resources to carry out each project.

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FAQ about Genome Sequencing and Analysis Centers (U54) (RFA-HG-10-015)

  1. What is the cost cap for each application?

    The previous cap was $45M direct cost /year/application. This has been changed to $65M total costs. Please see Notice of Correction to Award Budget information for NHGRI Sequencing Funding Opportunity Announcement RFA-HG-10-015.

  2. What distinguishes this FOA from the others listed here that request substantial amounts of sequencing?

    RFA-015 is the most direct continuation of the current NHGRI Large-Scale sequencing program. It requests applications from Centers that are flexible enough to be able to carry out any type of sequencing project, from design through analysis. In addition, these Centers are expected to continue to drive the state-of-the-art in production sequencing, from adopting and optimizing new platforms to testing and optimizing new applications on those platforms, etc. Accordingly, these awards will be substantial, and it is likely that the goals will only be attainable by very large production groups--for example, those that have very efficient production processes subject to continual internal improvement; that have considerable existing infrastructure including computational infrastructure for dealing with multiple terabases of data; that have dedicated technology and process development teams or functions; and that have experience with a range of high-throughput sequencing projects across the spectrum of applications for sequencing.

    The other two sequencing FOAs (RFA-HG-10-016, RFA-HG-10-016) are aimed at 1) Mendelian disorders, which requires a limited range of designs; and 2) Medical sequencing exploration projects, in which the main goal is to establish projects that directly use sequence for the benefit of patient care, and in which sequence production is a component but not emphasized as a purpose or specific goal.

  3. Is this FOA open to new groups in addition to those already funded by NHGRI for large-scale sequencing?

    Yes. There are now a number of large-scale sequencing groups that are operating at very high throughput. Newer sequencing platforms enable higher throughput to be attained by a number of groups. In any case, selection of applications for funding will be made on the basis of the results of the review and the other funding criteria in the FOA.

  4. I want to propose a Center that works only on a specific disease or set of diseases; or: I want to propose a center that specializes in one mode of sequencing (e.g., whole genome shotgun sequencing; whole exome sequencing; organismal sequencing). Would that be responsive?

    Not to this specific FOA. We expect Centers to be able to undertake a wide variety of projects and designs, and also to change as the state-of-the-art enables different questions to be explored, requiring new project designs.

  5. I have an approach to sequencing that does not use one of the current commercial platforms. May I propose to use it?

    Yes, but you will need to establish that its capabilities are at least as good as those of the established platforms. Moreover, a Center would need to be able to establish that it can be flexible over time to adopt whatever platform is best for the range of applications that may be required.

  6. Can I subcontract the production sequencing?

    Yes, but it may be a challenge. You will need to demonstrate to reviewers that you understand the detailed technical aspects of how the platform performs, and the implications of that for data quality, downstream analysis, project design, and cost. All the points listed above about flexibility (i.e., need to carry out multiple project types/designs; expectation for process improvement over time/driving the state-of-the-art; etc.) still apply.

  7. What will the relationship be between the groups funded under this FOA and the groups funded under the other FOAs discussed here?

    The awardees for the sequencing FOAs will function in the context of a research network. It is likely that the large Centers will be asked to exchange information with the awardees for the other sequencing FOAs, for example with regard to technical information about sequencing production, analysis, and project design. There is also potential for interaction with the awardees for the ELSI FOAs around some ELSI issues.

  8. Will equipment be funded?

    Yes, within the overall budget of the award. However, equipment purchases must be included in the overall cost of sequence production, in reporting costs within the application.

  9. What criteria will be used to make funding decisions?

    The most important funding criterion will be the review Impact Score. In addition, NHGRI will consider the number of applications to be funded in the context of the overall strength of the program.

  10. Will this FOA be renewed after the four-year funding period?

    We do not know at this point. NHGRI evaluates its programs on a regular basis. Whether or not to issue a renewal will depend on many factors, most importantly the continuing scientific need for large, centralized sequencing and analysis Centers.

  11. The FOA requires that applicants submit a separate application for a Diversity Action Plan (DAP) in the form of a separate application to PAR-09-245 Initiative to Maximize Research Education in Genomics (R25). What is the deadline for the separate application?

    The standard dates for R25 applications are January 25th, May 25th, and September 25th. Applications for DAP's that will accompany the sequencing applications should be submitted May 25th, 2011. Both will be reviewed in time for funding decisions to be made.

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FAQ about Mendelian Disorders Genome Centers (U54) (RFA-HG-10-016)

  1. What is the cost cap for each application?

    It is $10M total cost /year/application. The NHGRI has reserved $10M for FY 2012 for this FOA, and intends to fund up to two Mendelian Disorders Genome Centers. The applicant should propose a budget of $10M per year in total cost. In the event that two Centers are awarded, the grantees will be asked to reduce the proposed budgets to share the $10M total funds per year.

  2. If two Centers are funded, will the funds be equally divided between the two Centers?

    There may or may not be equal division of funds. The decision will be based on review results and how the two Centers can complement each other.

  3. Is this FOA open to the current NHGRI-funded Sequencing Centers?

    Yes.

  4. You have suggested in the FOA a production reporting table posted at www.genome.gov/27541956. Is this table included in the 30-page limit for the proposed research objectives?

    Yes.

  5. What criteria will be used to make funding decisions?

    The most important funding criterion will be the review Impact Score. The following two factors are included in the review criteria, and are particularly important for making funding decisions: the likelihood that the proposed effort will contribute to and accelerate the discovery of the genetic basis of Mendelian disorders in human, and the quality of the plan to share research data and materials with the research community.

  6. Will this FOA fund sample collection activities?

    No, this FOA will not fund sample collection activities. It will fund the acquisition of existing samples, and the creation and maintenance of a public sample list.

  7. Is the NHGRI going to provide samples to the Mendelian Disorders Genome Centers?

    The NHGRI itself will not fund a separate sample solicitation effort to provide for the Mendelian Disorders Genome Centers. However, samples may become available through efforts funded by other NIH institutes, and in that case program priority might necessitate that those samples be given priority in the sequencing pipeline. Note though, the NHGRI at this point anticipates that those samples may not take up a lot of the Centers' sequencing capacity. As stated in the FOA, the applicant is expected to solicit enough samples for the proposed sequencing capacity during the entire funding period with available funds.

  8. Is it permissible to use samples that were collected without individual identifiers or for which individual identifiers no longer exist (so that it will not be possible to return results to clinicians or participants)?

    Since this FOA focuses on the discovery of genetic variants underlying Mendelian disorders and not on returning research results for patient care, samples without identifiers that represent Mendelian disorders for which the molecular basis is unknown may be used.

  9. Is the sample solicitation plan expected to be focused on US population? Will samples from outside the US be acceptable and are there any special issues regarding informed consent?

    This FOA solicits proposals to discover the genetic variants underlying as many as possible Mendelian disorders and health-related Mendelian phenotypes. It is not intended to support only studies of diseases diagnosed in the US. Thus, diversity in the solicited samples is encouraged. Samples from outside the US are acceptable and the IRB of the institution that will be submitting the data to dbGaP is responsible for evaluating whether or not the informed consents used to collect the samples are adequate to permit public deposition of the data in a controlled access database. Finally, note that, since this FOA does not allow foreign components, you will not be able to have collaborators from foreign countries as subcontractors.

  10. Can you explain how the acquired human samples and those listed on the public sample list are expected to be shared with the public? Can you expand on what type of materials is to be shared with the research community?

    The applicant is expected to bring on board at least enough samples for the initial six months of the funding period and acquire more existing samples for the entire funding period. These samples are primarily intended for the use of the funded center's genetic variant discovery efforts. Note that the "Description of available samples" was placed under "Plan for Sharing Research Resources" in the Appendix section of the FOA as a result of some FOA format considerations. It is not an indication that the acquired samples must be broadly shared.

    The public sample list is intended to serve as a point of coordination for genetic variant discovery efforts that will be carried out by many groups. It should be annotated with information such as sample availability, sample form (tissue, DNA, e.g.), contact information for the sample custodian, etc. It is expected that researchers will contact the custodians of samples of their interests using the information provided in the sample list.

    For other types of materials to be shared with the research community, please see the related policies mentioned under "Plan for Sharing Research Resources" in the Appendix section of the FOA.

  11. If the funded centers generate cell lines or other materials and then submit them to sample repositories, will they be compensated with additional funds?

    Assuming that the informed consent for a given set of samples allows in vitro propagation and further distribution of the acquired samples, the NHGRI will explore the possibility of obtaining additional funds for this activity. However, there is no guarantee that this will be a fruitful attempt. The funded centers will also be encouraged to explore additional funds for this activity.

  12. You state in the FOA that detailed description of the available samples and what will be acquired can be provided as an appendix to the description of research objectives. Is there a format that you require for the sample list? What information items should I include in the description of samples?

    While the NHGRI does not require that you use a specific format to describe available samples and what you will acquire, you are encouraged to make a reader-friendly list of samples. For example, you could consider using Excel Spreadsheet and creating columns in the sheet for informative items. Information about the samples, and whether or not you have obtained commitment from sample custodians to provide the samples for the proposed research, will be helpful for the reviewers of your application. More specifically, columns for the following information will be helpful: OMIM identifiers (if that exist), sample custodians, diagnosis, assumed inheritance patterns, available pedigrees and individuals, status on consent for data release, and whether or not you have obtained letters of support from sample custodians. If you wish to provide letters of support, please only provide those from major sample providers.

  13. Can I subcontract the production sequencing?

    Yes, and the capabilities of the sequence data generator should be described in the application. In addition, you will need to demonstrate to reviewers that you understand the project design, detailed technical aspects of how the sequencing platforms perform, and implications of that for data quality, data analysis, and cost. You will also need to demonstrate to reviewers that you will be able to take advantage of the evolving sequencing technologies, which may not be implemented at the subcontractor's facility within an ideal time frame for your proposed center.

  14. You describe in the FOA whole exome sequencing as the current state-of-the-art for the discovery of genetic variants underlying Mendelian disorders. Can I propose to use a different approach for the same discovery purpose?

    Yes, and such applications should provide justification, for example, in terms of reasonable and credible advantages in cost and/or quality, for the proposed approach. The most competitive applications will be those that can demonstrate the highest potential to meet the research objectives with the available funds.

  15. Will this FOA support downstream data analysis once the genetic variants have been identified?

    This FOA will not provide adequate funds for complete characterization of every Mendelian disorder under study once the genetic variants have been identified. The applicant is encouraged to collaborate with the broader research community on downstream data analysis.

  16. In addition to DNA sequencing, can I propose RNA sequencing as part of the research plan?

    Note that this FOA will not provide adequate funds for complete characterization of identified genetic variants. You can propose RNA sequencing as long as you can justify as to why RNA sequencing will help identify the genetic variants underlying Mendelian disorders.

  17. Can I propose to use existing equipment for the proposed center? Will new equipment be funded?

    Yes, you can propose to use existing or new equipment, or a combination of both. Equipment purchases will be funded within the overall budget of the award. Note that equipment amortization should be included in the overall cost of sequence production.

  18. Is there an explicit additional consent required for data deposition into dbGaP? What about data generated from children? What about data generated from deceased individuals?

    The NIH expects its grantees to follow their institutional policies and local IRB rules regarding public data release and regarding the release of data generated from children or from deceased individuals. The institutions will be required to submit to the NIH their institutional certifications that approve data submission to the NIH data repository.

  19. Will this FOA be renewed after the four-year funding period?

    The NHGRI does not know the answer to this question at this time. The decision on renewal will be based on progress made toward the goals of the FOA, the overall progress made in the research field toward elucidating the genetic basis of most or all Mendelian disorders in human, as well as funding availability.

  20. Is there an ELSI component in this FOA?

    There is not an ELSI component in this particular FOA. For separate funding opportunities available through the NHGRI ELSI Research Program, please visit www.genome.gov/10001618.

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FAQ about Clinical Sequencing Exploratory Research (U01) (RFA-HG-10-017)

  1. What criteria will be used to make funding decisions?

    In addition to the standard criteria, e.g., significance, approach, etc., applications that successfully integrate the 3 Projects (Clinical Genomics Study, Sequence Analysis and Interpretation, ELSI) to produce a cohesive research program will receive greater enthusiasm.

  2. Will this FOA be renewed after the four-year funding period?

    The Clinical Sequencing Program is being launched with this exploratory research FOA. NHGRI staff anticipates that this area of research will grow and will have a long-term presence in the NHGRI portfolio. Therefore, reissuance of the FOA, with modifications as the field advances, is likely.

  3. Are all three Projects required?

    Yes, and they must be well integrated. The strength of each component and the degree of integration among components will be considered in the review.

  4. Should the lead investigator for each Project be designated a Principal Investigator (P.I.)?

    The investigator heading the clinical research must be designated a P.I. There is no requirement for the P.I. designation for the lead investigators for the Sequence Analysis and the ELSI Projects. However, the investigator leading each Project is expected to commit substantial effort to this grant, and should indicate an annual level of effort of at least 1.2 person/months. Furthermore, the usual NIH criteria for Investigators (see Scored Review Criteria in the FOA) will be a review consideration for the lead investigator for each Project.

  5. Is cancer an acceptable medical concentration for Project 1?

    Yes. Analysis of somatic mutations is responsive. Considerations for analyzing and communicating germline variation, should also be described.

  6. Can the genomic sequencing be done by contract?

    Yes. Generation of the genomic sequence data may be done by any organization that can satisfy the quality and quantity required by the research plan. The capabilities of a sequencing facility, in-house or by contract, should be described in the application.

  7. A direct cost cap of $1.5M/yr/grant and a total NHGRI set aside of $5.5M/yr suggests that a maximum of 3 awards can be made. Correct?

    NHGRI has preliminarily allocated $5.5M/yr for 4 years to support the awards from this FOA. However, NHGRI may choose to reallocate funds if necessary to support the most meritorious research.

  8. Are equipment costs permitted for the purchase of sequencing instruments?

    Capital equipment budget allocation is not prohibited. However, any departure from the cost cap provided in the FOA must be thoroughly justified and will be a staff funding consideration.

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FAQ about Development of a Preliminary Evidence Base to Inform Decision-making about Returning Research Results to Participants in Genomics Studies (R01) (RFA-HG-11-003)

  1. How is this FOA different from the ELSI component of RFA-HG-10-117 (U01)?

    This FOA is designed to stimulate empirical research to develop a preliminary evidence base to inform decision-making about whether, when, and how to offer to return individual research results to participants in genomic research studies (especially whole exome or whole gene sequencing studies) or to individuals who have provided samples or data for genomic repositories. By contrast, RFA-HG-10-117 invites applications for large projects designed to generate, process, filter, and interpret data from whole exome or whole genome sequencing in the specific context of an active clinical setting, and to return —and investigate the psychosocial and behavioral implications of returning —genomic results in the clinical setting (as distinct from the traditional research setting).

  2. How is this FOA different from RFA-HG-11-004 (R21)?

    This FOA is designed to stimulate empirical research to develop a preliminary evidence base to inform decision-making about whether, when, and how to offer to return individual research results to participants in genomic research studies (especially whole exome or whole gene sequencing studies) or to individuals who have provided samples or data for genomic repositories. This FOA is aimed primarily at investigators who propose behavioral or social science research projects in which there is likely to be direct interaction with research participants or other stakeholders involved in current, ongoing genomics projects or in genomic sample or data repositories. By contrast, RFA-HG-11-004 invites applications that propose to analyze the normative and legal issues involved in decision-making about returning research results. That FOA is aimed primarily at sole investigators or small teams of investigators who propose modest legal and normative research projects.

  3. Would an application be responsive to this RFA if it proposes to investigate the responses of research participants to being offered research results where no incidental findings (i.e., findings that relate to a disorder other than the disorder that is the direct subject of the research) will be involved?

    No. If the study will investigate the responses of research participants to being offered research results, then the underlying study should be one where at least some incidental findings that are potentially clinically actionable have been or are likely to be generated. Although the treatment of non-incidental findings is also a topic of importance, the issues associated with the treatment of incidental findings are likely to be particularly challenges; thus, the treatment of this these types of findings are an important focus of the RFA.

  4. As part of my application, can I request funds to support the recruitment of human subjects of genomic studies, the collection of genomic samples or data, or the collection of medical or phenotype data?

    No.

  5. If results will be offered to some or all participants as part of the study design of the underlying genomics study but the original informed consent did not clearly anticipate the sharing of this information, can I request funds to obtain reconsent as part of my application?

    Yes.

  6. If results will be offered to participants as part of the design of the underlying study and the research that generated the findings was not performed in a CLIA-certified laboratory, can I request funds to obtain confirmatory testing of research results in a CLIA-certified laboratory as part of my application?

    Yes.

  7. Can I submit an application for both this FOA and RFA-HG-11-004? Can I submit an application for this FOA and also be listed as a co-investigator on an application submitted for RFA-HG-10-117?

    Yes. However, each application submitted must propose a distinct research project. Two or more applications submitted by the same investigator that propose substantially the same research will not be accepted.

  8. What criteria will be used to make funding decisions?

    This FOA will use the standard review criteria for R01 applications. Funding decisions will be based on the priority score, the need for programmatic balance, and other considerations as appropriate.

  9. Will this FOA be renewed after the initial funding period?

    A decision about whether the FOA will be renewed has not yet been made.

  10. Will investigators funded under this FOA have an opportunity to interact with other investigators funded under this FOA and with the investigators funded under the other FOAs listed above?

    Yes. A consortium will be organized that includes the principal investigators and relevant key personnel funded under this FOA; this consortium will also include other investigators who are already working on these issues, as well as the investigators to be funded under RFA-HG-10-117 (U01) and RFA-HG-11-004 (R21). There is also some potential for interaction with the awardees of RFA-HG-10-015 (U54) and RFA-HG-10-016 (U54).

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FAQ about Ethical, Legal, and Social Implications of Returning Research Results to Genomic Research Participants (R21) (RFA-HG-11-004)

  1. How is this FOA different from the ELSI component of RFA-HG-10-117 (U01)?

    This FOA is aimed primarily at sole investigators or small teams of investigators who propose modest analytical research projects on the normative and legal issues involved in deciding whether, when, and how to offer to return individual research results to participants in genomic research studies (especially whole exome or whole genome sequencing studies) or to individuals who have provided samples or data for genomic repositories (such as biobanks or databases). By contrast, RFA-HG-10-117 invites applications for large projects designed to generate, process, filter, and interpret data from whole exome or whole genome sequencing in the specific context of an active clinical setting, and to return — and investigate the psychosocial and behavioral implications of returning — genomic results in the clinical setting.

  2. How is this FOA different from RFA-HG-11-003 (R01)?

    This FOA is designed to stimulate analytical research on the normative and legal issues involved in deciding whether, when, and how to offer to return individual research results to participants in genomic research studies (especially whole exome or whole genome sequencing studies) or to individuals who have provided samples or data for genomic repositories (such as biobanks or databases). This FOA is aimed primarily at sole investigators or small teams of investigators who propose modest legal and normative research projects. By contrast, RFA-HG-11-003 (R01) invites applications that propose empirical research to develop a preliminary evidence base to inform decision-making about returning research results. That FOA is aimed primarily at investigators who propose behavioral or social science research projects in which there is likely to be direct interaction with research participants or other stakeholders involved in current, ongoing genomics projects or in genomic sample or data repositories.

  3. The RFA states that applications submitted under this announcement may incorporate a small, exploratory empirical research component, but that in most cases, applicants proposing empirically focused studies should consider applying instead under RFA-HG-11-003 (R01). I am interested in conducting an exploratory study that will directly inform consideration of the normative or legal issues involved in returning research results to participants in genomic research studies, but the study would be primarily an empirical one. Yet the empirical study I would like to do does not seem as if it would be responsive to RFA-HG-11-003 (R01) because it is relatively small and it would not necessarily involve direct interaction with participants in an ongoing genomic research project. Would such a study be responsive to this R21 RFA?

    In some cases, yes, but you should contact program staff for further guidance if you are considering such a study to discuss your plans. The R21 mechanism is targeted primarily toward normative and legal scholars. However, in some limited circumstances, other kinds of small, highly focused studies may also be appropriate, even if the methods are mostly empirical.

  4. Can I submit an application for both this FOA and RFA-HG-11-003? Can I submit an application for this FOA and also be listed as a co-investigator on an application submitted for RFA-HG-10-117?

    Yes. However, each application submitted must propose a distinct research project. Two or more applications submitted by the same investigator that propose substantially the same research will not be accepted.

  5. What criteria will be used to make funding decisions?

    This FOA will use the standard review criteria for R21 applications. Funding decisions will be based on the priority score, the need for programmatic balance, and other considerations as appropriate.

  6. Will this FOA be renewed after the initial funding period?

    A decision about whether the FOA will be renewed has not yet been made.

  7. Will investigators funded under this FOA have an opportunity to interact with other investigators funded under this FOA and with the investigators funded under the other FOAs listed above?

    Yes. A consortium will be organized that includes the principal investigators and relevant key personnel funded under this FOA; this consortium will also include other investigators who are already working on these issues, as well as the investigators to be funded under RFA-HG-10-117 (U01) and RFA-HG-11-003 (R01). There is also some potential for interaction with the awardees of RFA-HG-10-015 (U54) and RFA-HG-10-016 (U54).

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Last Updated: January 27, 2012