Required Application Instructions

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The National Human Genome Research Institute (NHGRI) will fund a new Genome Sequencing Program (GSP) through multiple FOAs: HG-015-001 for Centers for Common Disease Genomics (CCDG) and RFA-HG-015-002 for Centers for Mendelian Genomics (CMG). The overall aim of the GSP as a whole is to use genome sequencing to identify genes and genomic variants underlying human inherited disease. The CCDG will be doing this for multiple examples of common human inherited diseases. They will explore a range of project designs and a range of presumed underlying genomic architectures, as comprehensively as possible. In so doing they will develop resources for the community and develop and optimize technical and project design approaches for using genome sequencing to understand common disease. The CMG will identify genes and variants underlying hundreds of Mendelian conditions, and in so doing will also develop tools and know-how relevant to applying genome sequencing to Mendelian disease. In addition, the NHGRI plans to add a separate component to the GSP that will be involved in analyses of the data that take advantage of the range and volume of the data being produced by the program as a whole (see http://www.genome.gov/Pages/About/NACHGR/February2015AgendaDocuments/GSP_Feb_2015_Concepts.pdf for the archived Concept document for this component).

The NHGRI GSP will have multiple components, each working on multiple projects, some of which will be carried out by multiple centers. NHGRI expects the GSP as a whole to produce results both for the individual projects, and also for several cross-program goals. Thus the needs for coordination across the program will be high.

With this FOA, NHGRI seeks to fund a GSP Coordinating Center (GSPCC) that will have two broad roles in coordinating the activities of the overall GSP, and in helping to ensure that their efforts are productive and provide useful outcomes for the scientific community, and in general to enhance the potential for success of the program. The two roles are:

I. Providing scientific leadership for specific cross-program scientific objectives that are expected products of the GSP program as a whole:

• In the context of the CCDG efforts, the GSPCC will lead a consensus analysis to address the question: "When is a common disease variant discovery study effectively complete?". As discussed in RFA-HG-015-001, this will inevitably require consideration of both scientific factors (e.g., statistical power, underlying disease architecture, study designs considerations, what can we learn from obtaining data from additional samples/populations; how far can such studies go in identifying) and practical factors (e.g., cost; technology platforms). NHGRI understands that it may not be possible to converge on a single answer. However, we do intend that the program will provide--at the least--an informed analysis, backed up by data, that defines the state of the art and the costs and benefits of adding additional data to a project in both quantitative and qualitative terms. This is an important outcome for many reasons, not least because there is currently wide interest in investing very significant resources over the next several decades on discovery and characterization of variants underlying inherited diseases, commensurate with their importance for public health.
• The GSPCC will develop specifications for development of a set of common controls for common disease rare variant studies. Applicants should propose methods for developing a plan and facilitating consensus around the specifications for common controls. Availability of a well-characterized, widely applicable set of common controls would significantly reduce costs of many future study designs. As above, both scientific considerations (e.g., need to match or harmonize variant and phenotype data; need to match populations; sample numbers, power, etc.) and practical considerations (e.g., cost, sample availability) will arise. The full task of developing a set of common controls may be too large for this FOA; we therefore aim to begin by tasking the GSPCC with developing design considerations for a broadly generalizable control set, based on the projects that will be undertaken by the production centers. Because the GSP will be producing large volumes of data in the context of such studies, it represents a good context within which to develop specifications and general recommendations for such a control data set (although we expect that any such effort will consider all useful data whether it comes from within the GSP or not).
• In the event that this analysis can be completed within the initial year or two of the program, NHGRI is open to the possibility that the goal can be advanced, from developing specifications for common controls, to developing the resource.
• The GSPCC will be responsible for producing allele frequency data for the CMG program. Twice each year, the CMGs will provide genome sequence and associated data to the GSPCC in a standard format (likely BAM file). The GSPCC will be expected to calculate allele frequencies from the data. In addition, the CC and the CMGs are expected to work out a way to share and summarize associated phenotype information. Then the CC will be responsible for making the allele frequencies and associated high level phenotype information publically available.
• The GSPCC will be asked to provide input into other cross-program activities that may arise, which will require scientific expertise. In general a successful GSPCC will work with GSP investigators and NHGRI staff to help ensure that the results are integrated, including helping to reconcile differences in analyses (for example, different variant call sets on the same data), or looking for ways to synergize across sample sets (e.g., being sequenced by multiple CCDG's) with similar phenotypes. The GSPCC also will contribute scientific expertise and leadership as needed to facilitate cross-study activities in areas such as policy compliance, harmonization of phenotype and exposure measures, and facilitating consensus with regard to implications of disease causality of identified variants. The GSPCC will be encouraged to identify other useful analyses that will cut across multiple grantees or programs that may add value to the GSP, for example data quality assessments or design of arrays.

The GSPCC will be responsible for providing scientific leadership and coordination for these activities, and the applicant is expected to request funds associated with investigator time (including time needed for collaboration) and analyses that may be required to accomplish the goals above. However, it is critical to note that these functions must be carried out in collaboration with other components of the GSP; in fact the other components will need to be actively enlisted because GSPCC funds are limited. The GSPCC is not necessarily required to include specific analytic expertise to carry out each one of the activities mentioned herein (with the exception of the allele frequency analysis for the CMG), but rather will need to understand the activities to the extent that they can help coordinate and facilitate specific expertise that exists within the program as a whole. Consistent with this, several of the cross-program goals above are also mentioned in the CCDG FOA and will also be included in any FOA for planned GSP-associated analysis centers. However, of all the GSP components, only the GSPCC is given leadership responsibility for accomplishing the cross-program goals listed above.

The GSPCC will not be responsible for analyses of individual projects undertaken by the CCDG and CMG.

It is important that applicants be aware that the GSP is intended to be highly collaborative both within and outside of the GSP program, and that scientific opportunities may arise that involve interactions with other large data-generating genomics programs, such as the Electronic Medical Records and Genomics Network (eMERGE http://www.genome.gov/27540473) or the Clinical Sequencing Exploratory Research Program (CSER http://www.genome.gov/27546194).

Because of the scientific roles discussed above, and the need to facilitate consensus among multiple groups, NHGRI believes that it is important that the GSPCC be independent of the CCDG and the CMG awardees. This will be reflected in the eligibility and funding criteria.

II. Providing coordination for administrative, logistical, and outreach activities:

• The GSPCC will work collaboratively with the GSP investigators, investigators in other relevant NHGRI programs as scientific opportunities arise, as well as with NHGRI staff to facilitate a comprehensive program of research to promote discovery of disease-related variants and elucidation of their potential causal role.
• The GSPCC will work with NHGRI program staff to track genome sequencing and analysis costs, production, data deposition, and project completion.
• The GSPCC will be a resource for logistics and communication among GSP program participants and collaborators, including scheduling conference calls, recording minutes and action items as needed, working with NHGRI staff to develop web resources for cross-program working groups (e.g., distributing and archiving working group documents) or projects as needed, planning program meetings and generating and distributing relevant documents, etc.
• The GSPCC will arrange and coordinate outreach activities for the GSP. This will include public web views of progress on project status (including phenotypes in the CMG pipeline), where to find project data, causal variant information, publication lists, Frequently Asked Questions, etc. The GSPCC will provide assistance in summarizing and communicating to the community general lessons learned about how to use genome sequencing to find rare variants, and help with ensuring that project data are available to the wider community. This objective may also include help organizing community workshops (when appropriate) regarding data resources generated by the GSP, or regarding selection of new projects for the CCDG.

In accomplishing the objectives above, applicants should bear in mind that the GSPCC will need to work closely with other program awardees and with NHGRI program staff. In addition, a number of the individual projects undertaken by the GSP will involve outside collaborators. For example, many of the individual CCDG projects will entail collaborations with study investigators funded by other entities, including other NIH institutes. These collaborators may be embedded in consortia that are already established, and that have their own coordinating functions (for example, a community data portal). All GSP components, but especially the GSPCC will need to work flexibly with these consortia in order to make the most efficient use of NHGRI resources. As a consequence, the GSPCC may have a significant coordination role for some projects and activities, but will not be required as intensively for others. NHGRI Staff will work closely with the GSPCC to facilitate this.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
  • NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons. If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

PD/PIs and organizational entities who are from an institution that is a prime recipient of an award under RFA-HG-15-001 or RFA-HG-15-002 will be ineligible for funding under this FOA in order to ensure that the GSPCC is largely independent from those GSP components. However, PD/PIs from institutions that have applied to RFA-HG-015-001 or -002, but do not yet know whether they will receive funding, may still apply to this FOA. NHGRI will resolve funding eligibility at the time funding decisions are made.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Adam Felsenfeld
Telephone: 301-496-7531
Fax: 301-480-2770
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

The Biographical Sketch should address any previous experience in coordinating large complex research efforts.

All instructions in the SF424 (R&R) Application Guide must be followed.

Budget information should be described so that all items, including percentage of effort, can be clearly allocated to each of the two broad roles described in the Scope and Objectives section. NHGRI expects that the objectives discussed under "Providing coordination for administrative, logistical, and outreach activities" will require about 75% of the overall budget.

The PD/PI is required to devote at least 15% effort (1.8 mos) to this effort.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:

Research Strategy: Within the Research Strategy, applicants should address general considerations that are likely to lead to successful coordination of the overall GSP, and identify any synergies between the different objectives. Applicants should include a brief description of how the overall effort will be managed.

Applicants should also propose approaches to collaboratively address the two roles described in the Scope and Objectives (I. Providing scientific leadership for specific cross-program scientific objectives that are expected products of the GSP program as a whole; II. Providing coordination for administrative, logistical, and outreach activities) in separate sections.

The section on Providing scientific leadership should explicitly discuss plans for each of the cross-program scientific objectives set out in the Scope and Objectives section, namely evaluating when a large common disease variant study is comprehensive or complete; providing specifications for a set of common controls for common disease sequencing studies; producing an allele frequency analysis for data from multiple genome sequences from the CMG effort (including the plans to manage individual-level data from which these results will be derived), and the other specific cross-program objectives mentioned. This section may also propose and justify any additional cross-program analyses, not otherwise listed in the FOA, that applicants believe should be considered for the program. It is understood that applicants will not have data from the GSP in hand at the time of application, and that plans will necessarily need to make assumptions and describe proposed approaches. In addition, this FOA does not require applicants to propose to carry out all of, or every one of, the specific analyses needed to address the scientific cross-cutting objectives (with the exception of the allele frequency analysis for the CMG). However we do ask that applicants demonstrate enough scientific expertise in these areas that they can play a leadership role in ensuring that the cross-program scientific objectives will be met, drawing on expertise from other program components.

The section on Providing coordination should discuss how the listed activities in the Scope and Objectives will be accomplished, staffed and managed. Applicants are encouraged to describe how their plans in this section will leverage their experience described in the Biographical Sketch. Applicants are encouraged to propose and justify any other coordination activity that would be useful to the GSP, but is not listed explicitly elsewhere in this FOA.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

Applicants are expected to provide plans for any of the specific items in the Scope and Objectives related to making data available that are not otherwise described in the Research Plan, including plans for making the CMG allele frequency data available.

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

This U24 FOA will support a coordinating center for the NHGRI GSP program (GSPCC). The GSPCC will be asked to provide scientific leadership in accomplishing certain, specified cross-program scientific objectives defined in this FOA, and will also be asked to provide and coordinate administrative and logistical support. The overall GSP program will include three other components: Centers for Common Disease Genomics (CCDG) that will be producing sequence data and computationally identifying underlying genes and variants for multiple common, complex human diseases; Centers for Mendelian Genomics (CMG) that will be identifying genes and variants implicated in hundreds of Mendelian conditions; and a planned set of analysis grants that will propose their own analyses that take advantage of all the data produced by the GSP. None of these other components will be funded before this FOA is reviewed.

Applicants will not have data from the GSP at the time the GSPCC application is written, so applications will necessarily need to make assumptions and describe proposed approaches in general terms. In addition, this FOA does not require applicants to propose to carry out all of, or every one of, the specific analyses needed to address the scientific cross-cutting objectives (with the exception of the allele frequency analysis for the CMG, which the GSPCC is expected to carry out independently). However we do expect that applicants demonstrate enough scientific expertise in these areas that they can play a leadership role in ensuring that the cross-program scientific objectives will be met, drawing on expertise from other GSP components. Applicants also may propose their own, additional cross-program analyses and coordinating activities.

Because this FOA is for a coordinating center, it is critical that all proposed objectives be carried out collaboratively with the other components of the GSP (who will have funds available to contribute to the cross-program goals) and NHGRI staff.

Accordingly, reviewers will focus their evaluation on the potential for providing scientific expertise and leadership for the listed cross-program objectives, and the ability to provide coordination to aid the complex GSP in accomplishing its major objectives.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Is the proposed Center likely to significantly enhance the goals of the research program it proposes to serve (the GSP), both with regard to attaining the scientific cross-cutting program objectives, and the coordination, administrative, logistical, and outreach objectives? Will it facilitate or expedite research that would be delayed or infeasible if conducted as independent projects? What advantages will the Center bring to the research program?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated an ongoing record of excellence in managing large research projects? If the Center is collaborative or multi-PD/PI, do the investigators have complementary and integrated skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center described

Do the investigators have experience in successfully coordinating and collaborating with efforts of comparable size and complexity? Do the investigators have expertise in the areas covered in the scientific objectives of this FOA?

Are the PD(s)/PI(s) and any key investigators likely to be able to accomplish all the objectives in a highly collaborative, fair, and flexible manner, appropriate to the coordinating center roles described in this FOA?

Does the application propose novel organizational concepts, management strategies, or instrumentation in coordinating the research program the Center will serve? Are the concepts, strategies, or instrumentation novel to one research program or applicable in a broad sense? Is a refinement, improvement, or new application of organizational concepts, management strategies or instrumentation proposed? ?

Does the applicant propose innovative approaches to accomplishing the cross-program scientific goals?

Are there innovative and useful approaches to project coordination, logistical, or outreach objectives?

Are the overall design, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research program the Center will serve? Are potential problems, alternative strategies, and benchmarks for success presented? If the Center is in the early stages of operation, will the strategy establish feasibility and will particularly risky aspects be managed?

Will the proposed project likely provide leadership for and aid in the accomplishment of the cross-program scientific goals of the NHGRI GSP? Will it be likely to lead to successful coordination of the overall GSP?

Throughout, are the proposed approaches likely to facilitate consensus among or otherwise work collaboratively with the other components of the overall program? Will these approaches be responsive to the changing needs of the program over time?

Are plans adequate for each of the cross-program scientific objectives (e.g., evaluating when a large common disease variant study is comprehensive or complete; providing specifications for a set of common controls for common disease sequencing studies)? Are plans adequate for other proposed analyses? Where applicants propose to lead and coordinate these analyses within the GSP as a whole, rather than carry them out themselves, does the plan convey that the applicant has the scientific expertise to effectively lead those efforts?

Are the plans adequate for producing an allele frequency analysis for data from multiple genome sequences from the CMG effort?

Do the plans for the objectives relating to providing and coordinating administrative and logistical support clearly set out how the multiple objectives will be accomplished, staffed and managed? Do the plans consider the likely size and scope of the overall GSP? Are they efficient and scalable? Will they be effective?

Does the application overall strike an appropriate and thoughtfully prioritized balance between the cross-program scientific objectives, and the coordination/administrative/logistic/outreach objectives?

If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research program it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, personnel, or collaborative arrangements?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the National Human Genome Research Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Advisory Council for Human Genome Research. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with resource sharing policies as appropriate
• Independence from investigators and institutions funded under two other components of the NHGRI GSP in response to RFA-HG-015-001 and RFA HG-015-002.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Grantees, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

The PD(s)/PI(s) will have the primary responsibility for:

• Defining, within the context of this FOA, objectives and approaches, and for planning, conducting, analyzing, and publishing results, interpretations, and conclusions of their studies.
• Agreeing to accept close coordination, cooperation, and participation of NHGRI staff in those aspects of scientific and technical management of the project as described under "NIH Staff Responsibilities";
• Adhering to the NHGRI policies regarding intellectual property, data release and other policies that might be established during the course of this activity (see http://gds.nih.gov/03policy2.html);
• Accepting and participating in the cooperative nature of the NHGRI Genome Sequencing Research Network composed of awardees to this FOA and other components of the NHGRI Genome Sequencing Program;
• Working productively with program staff from other NIH institutes who may be providing co-funding for projects;
• Working cooperatively with investigators that may be collaborating with the other components of the GSP including with data repositories or community data portals;
• Submitting progress updates in a standard format, as agreed upon by the Steering Committee and the External Scientific Advisors;
• Accepting and implementing any other common guidelines and procedures developed for the NHGRI GSP and approved by the Steering Committee and the External Scientific Advisors;
• Where opportunities are identified, participating in collaborations with other NHGRI research networks.
• Coordinating and collaborating with other U.S. and international groups engaged in large-scale genomic sequencing or other large projects when opportunities are identified by NHGRI staff;
• Informing the Program Director of all major interactions of members of the Steering Committee;
• Attending Steering Committee meetings and annual program meetings;
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below, during the conduct of this activity, in order to provide technical assistance, advice and facilitate coordination. However, the role of NHGRI will be to facilitate and not to direct the activities. It is anticipated that decisions in all activities will be reached by consensus of the GSP Research Network (composed of all grantees funded by GSP programs, with the possible inclusion of grantees from other collaborating NHGRI-funded programs) and that NHGRI staff will participate fully in this process.

The Project Scientist will:

• Participate (with the other Steering Committee members) in the group process of setting research priorities, deciding optimal research approaches and protocol designs and contributing to the adjustment of research protocols or approaches as warranted. The Project Scientist will assist and facilitate the group process and not direct it;
• Negotiate goals, including timelines, with all program awardees as necessary;
• Manage the processes for selecting new Projects for the CCDG program;
• Provide templates for gathering information about progress within the CCDG and CMG components. The GSPCC will aid in gathering data for, presenting, and summarizing, such reports, based on the NHGRI staff-provided templates.
• Serve as a liaison between the awardees and the External Scientific Panel, the National Advisory Council for Human Genome Research;
• Coordinate the efforts of the awardees with other awardees under this FOA and related NHGRI programs; with other NIH institutes and their research communities, and with the international genomics community;
• Attend all Steering Committee meetings as a voting member and assist in developing operating guidelines, quality control procedures, and consistent policies for dealing with recurrent situations that require coordinated action;
• Periodically report progress to the Director, NHGRI;
• Lend relevant expertise and overall knowledge of NHGRI-sponsored research to facilitate the selection of scientists not affiliated with the awardee institutions who are to serve on the External Scientific Panel; serve as liaison between the Steering Committee and the External Scientific Panel;
• Serve on subcommittees of the Steering Committee and the External Scientific Panel, as appropriate;
• Provide advice on the management and technical performance of the investigation;
• Assist in promoting the availability of the genome sequence data and related resources developed in the course of this project to the scientific community at large;
• Participate in data analyses, interpretations, and where warranted, co-authorship of the publication of results of studies conducted through the Genome Sequencing Research Network;
• Assist awardees in the development, if needed, of policies for dealing with situations that require coordinated action;
• Retain the option to recommend, with the advice of the External Scientific Panel, the withholding or reduction of support from any cooperative agreement that substantially fails to achieve its goals according to the milestones agreed to at the time of award, fails to maintain state-of-the-art capabilities, or fails to comply with the Terms and Conditions of the award.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The assigned program director may also serve as the NIH Project Scientist.
• Additionally, an agency program official or IC program director will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice.

Areas of Joint Responsibility include:

Participation in the Steering Committee. A Steering Committee will serve as the main governing board of the GSP Research Network. The Steering Committee membership will include the NHGRI Project Scientist(s) and one P.I. from each awarded cooperative agreement for the CCDG, the CMG, and the GSPCC. If other GSP components are created, they may be included in the Steering Committee. In some cases where co-funding has been provided, NHGRI may include program staff from other NIH institutes. The Steering Committee Chair will not be an NIH staff member. Additional members may be added by action of the Steering Committee. Other government staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. Because the Research Network will include investigators funded by this FOA and other FOA's for the NHGRI Genome Sequencing Program, it is possible that NHGRI staff will create appropriate subcommittees to handle interests that may be specific to a set of awardees under a specific FOA.

The Steering Committee will:

• Discuss progress in meeting the objectives of the program;
• Develop recommendations for uniform procedures and policies necessary to meet the goals of the Research Network, for example for data quality measures and assessment, conventions for data deposition, or measuring costs and throughput.
• Develop recommendations about the types of data analyses to be done and how best to achieve them.
• Adoption of procedures and policies developed by the Steering Committee will require concurrence by the External Scientific Panel;
• Serve as a venue for coordination on the improvement of the ability to carry out comprehensive common disease rare variant studies or other cross-program objectives.
• Serve as a venue for coordination on improvements in genomic sequencing, for example by disseminating best practices and collectively evaluating new procedures, resources, and technologies.
• Schedule the time for, and prepare concise summaries of, the Steering Committee meetings, which will be delivered to members of the group within 30 days after each meeting.
• Each full member (one person for the GSPCC in the case of multiple PI s) will have one vote except NHGRI Project Scientist(s), who will have one collective vote.
• Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.

Another area of joint responsibility is that NHGRI and the grantees will work with and provide information to an External Scientific Panel (ESP). The ESP will be responsible for reviewing and evaluating the progress of the members of the Genome Sequencing Research Network toward meeting their individual and collective goals. The ESP will provide recommendations to the Director, NHGRI, about continued support of the components of the Genome Sequencing Research Network. If funds are withheld by NHGRI for programmatic reasons, rather than performance reasons, the ESP will provide advice to NHGRI regarding the distribution of those funds. The ESP is composed of six to ten senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the Genome Sequencing Research Network. The membership of the Scientific Advisory Panel may be enlarged permanently, or on an ad hoc basis, as needed.

The ESP will meet at least once a year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the Scientific Advisory Panel members to interact directly with the awardees. The ESP will make recommendations regarding progress of the Genome Sequencing Research Network and present advice about changes, if any, which may be necessary in the Genome Sequencing Research Network program to the Director, NHGRI.

Dispute Resolution:

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel composed of three members will be convened. It will have three members: a designee of the Steering Committee chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Finding Help Online: http://grants.nih.gov/support/index.html
Email: [email protected]

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GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Adam Felsenfeld
National Human Genome Research Institute (NHGRI)
Telephone: 301-596-7531
Email: [email protected]

Rudy Pozzatti
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8739
Email: [email protected]

Cheryl Chick
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-785
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.