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: RFA-HG-15-001 for Centers for Common Disease Genomics (CCDG), RFA-HG-015-002 for Centers for Mendelian Genomics (CMG), RFA-HG-15-019 for a Genome Sequencing Program Coordinating Center (GSPCC) (all three to be funded in late 2015), and the present FOA for the Genome Sequencing Program Analysis Centers (GSPAC).

The overall aim of the GSP is to use genome sequencing to identify genes and genomic variants underlying human inherited disease. The CCDG will be doing this for multiple (5-10) 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. At the present time, NHGRI expects that the CCDG program will produce whole genome sequence data for over 200,000 samples, and may also produce substantial whole exome data.

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. At this time, the CMG program is expected to produce sequence data on between 25,000 and 50,000 samples, most of which will be whole exome data, and may also produce whole genome data.

The GSPCC will provide scientific leadership in accomplishing specified cross-program scientific objectives, will undertake allele frequency analysis for the CMG, and will also provide and coordinate administrative and logistical support across the GSP.

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 for the individual projects, and also to work towards cross-program goals.

The GSPAC will be the fourth component of the overall GSP. It will undertake analyses that take advantage of the range and volume of the data being produced by the program as a whole, as briefly described above. The GSPAC is designed to have several features: a substantial investigator-driven component with a scope that is wider than the analysis goals of the individual CCDG or CMG programs, and a more collaborative component aimed at two defined cross-program questions (detailed elsewhere in this FOA). Finally, the GSPAC concept includes the idea that the GSP, and the field as a whole, will benefit from having the substantial program data, and the analyses that they support, used and undertaken by those outside of large genome sequencing centers. (see

http://www.genome.gov/Pages/About/NACHGR/February2015AgendaDocuments/GSP_Feb_2015_Concepts.pdf for the archived Concept document for this component).

NHGRI seeks to establish NHGRI Genome Sequencing Program Analysis Centers (GSPAC), which will undertake computational analyses of the data produced by the NHGRI GSP. These analyses are expected to explore areas that cut across the individual projects and grants that are the primary data producing constituents of the overall GSP. GSPAC will pursue topics that are of broad applicability to the interpretation of genomic sequencing studies for understanding the biology of disease, are aimed at goals that are not specific to any particular disease, and may produce secondary or derived datasets, or analysis methods, that are of high interest to the genomics community. Moreover, GSPAC are expected to undertake work that takes advantage of all, or a substantial subset, of the diverse data produced by the other program components (i.e., by the CCDG, the CMG, or both). These analyses may also use other existing genomic datasets, for example from ENCODE (https://www.encodeproject.org/), eMERGE (https://emerge.mc.vanderbilt.edu/), GTEx (http://www.gtexportal.org/home/) or other projects.

This FOA seeks applications that propose two different kinds of activities: investigator-driven and program-driven. Each Analysis Center is expected to propose work relevant to both types of activity.

• Investigator-driven: GSPAC will develop and undertake significant, novel high-level analyses and development of related methods for all non-automated aspects of characterizing sequence variants in the data, after variant calling. For this activity, applicants are at liberty to propose work that goes beyond the scope of the analysis work that will be funded through the other GSP components. Analysis Center topics will be initiated, proposed and justified by the applicants. However, NHGRI has particular interest in questions about identifying associations between variants and disease phenotypes; analyses using existing functional data to leverage associations and/or to make functional inferences; means to improve study design; and other higher level analyses. It is expected that each Analysis Center will focus on one or more of these topics; NHGRI expects that, as a group, the GSPACs will cover multiple, diverse topics.
  
  Because of the importance of undertaking projects with broad significance and general applicability, applications proposing work on a single disease are not likely to be appropriate for this FOA.
  
  
• Program-driven: The second activity of the GSPAC will be to contribute to two cross-program goals: delineating when a common, complex disease study is comprehensive, and providing specifications for a set of common controls for such studies. The other program components ---CCDG, CMG, and the GSP GSPCC---will also collaborating on those defined cross-program goals.

NHGRI understands that these two activities may have useful scientific overlap, and also will encourage the identification of new cross-program goals as part of the work of the GSP. Because this FOA will fund a component of a larger program, it is important that the proposed work for both activities be carried out collaboratively with the other components of the GSP and with NHGRI staff.

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
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• U.S. Territory or Possession

Other

• Native American Tribal Organizations (other than Federally recognized tribal governments)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are 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 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 GSP Analysis Centers are largely independent from those two 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, but they are cautioned that they will not be able to receive awards from both FOAs.

PD/PIs and organizational entities who have received subaward/subcontract funding from recipients of RFA-HG-15-001 or RFA-HG-15-002 are eligible for funding under this FOA. .

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

Only one application per institution, (normally identified by having a unique DUNS number or NIH IPF number) is allowed.

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, Ph.D
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.

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, with the following additional instructions:

Research Strategy: Applicants should clearly delineate the parts of the application that address each of the two activities (investigator-driven and program-driven) described in the Purpose and Objectives; some parts of the application may apply to both activities. Although there are no requirements, as a guideline it is anticipated that the first (investigator-driven) activity will comprise the majority (approximately 80%) of the overall proposed budget. Applicants should describe how they will prioritize among and between activities.

Applicants should provide a clear description and justification for the significance of topics chosen as part of the investigator-driven activity, particularly if the topic is different from the ones mentioned to be of interest to NHGRI. Applicants should indicate how proposed analyses will add significantly to the value (e.g., characterization and interpretation) of the genomic datasets produced by the GSP. Applicants should indicate how the proposed work will advance the field of analysis of genome sequence and possibly other genome-scale data to significantly improve our ability to characterize sequence variants in the data. If extensive secondary or derived datasets will be produced as a result of the analyses, applicants should describe their likely value to the community.

Because the GSP will be a complex program, entailing collaborative interactions between multiple GSP components, and also outside study investigators (who will provide samples), applicants should describe how they plan to manage the necessary collaborative interactions. Applicants should refer to prior experience working within large consortia.

It is understood that, at the time GSPAC applications are submitted, applicants may only have a general idea of the types and amount of data that will be produced by the GSP (e.g., no specific information about specific studies, sample numbers for each phenotype, etc.). Applicants should therefore draw on knowledge about and examples from existing sequence datasets in describing preliminary studies, and clearly state assumptions and contingencies within the approach.

A note about data: Several important details about obtaining the GSP data, that would be useful for responding to this FOA, may be unclear prior to the application due date. Moreover, it is likely that certain details about the location and availability of data required for proposed analyses will continue to evolve during the award period, for example due to the sheer increase in the amount of genome sequence data produced, changes in technical capabilities, file formats, data policies, etc. Applications should acknowledge and account for this likelihood in their research strategy as they describe how they will obtain and treat data for analyses. Applicants should assume they will have access to project data in a way that is consistent with the NIH Genomic Data Sharing Policy (http://gds.nih.gov/03policy2.html). All sequence data are expected to be deposited in dbGaP, and available via project exchange areas to project collaborators; GSPACs will be treated as project collaborators (with attendant reciprocal rights and responsibilities) on all projects whose data they require. Data from individual projects may also be available to collaborators directly from individual CCDGs. There is currently no provision within the GSP for aggregation of the CCDG data (although the GSPCC will aggregate data required for it to perform allele frequency analysis for the CMG). Applicants may need to plan for accessing data separately for each individual project they wish to use. NHGRI anticipates that the needs for access to sequence data within the GSP, in the face of technical and policy changes, will drive discussions within the GSP about technical or organizational solutions over time.

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:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• For this FOA, applicants are expected to address how any secondary high-value datasets (i.e., the products of genome-scale analyses of sequence data produced by the NHGRI Genome Sequencing Program and possibly other data) will be shared.
• If the applicants propose to develop new computational tools or algorithms, applicants are expected to describe how they will be shared.

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 U01 FOA will support Analysis Centers for the NHGRI GSP program. The overall GSP program will include three other components: Centers for Common Disease Genomics (CCDG) that will produce sequence data on 200,000 samples or more, and computationally identify underlying genes and variants for multiple common, complex human diseases; Centers for Mendelian Genomics (CMG) that will produce whole exome data on 25,000 samples, or more, and identify genes and variants implicated in Mendelian conditions; and a Genome Sequencing Program Coordinating Center (GSPCC) that will provide scientific leadership in accomplishing cross-program scientific objectives, and will provide administrative and logistical support and coordination.

We expect these other components to be funded late in 2015; therefore, GSP Analysis Centers applicants will not have data from the GSP at the time their application is written/submitted. In particular, applicants will not know details such as the specific disease phenotypes that will be pursued across the program, what sample numbers or populations will be included in any particular disease study, what type of clinical or other phenotypic data will be available, etc. Applications will need to make assumptions about the data, and will need to describe some proposed approaches in general terms. However, it is reasonable to expect that applicants are familiar with the scope of the GSP as outlined in this and the other GSP FOAs, and applicants may refer to existing sequence or other data sets in describing preliminary results.

Reviewers should note that this FOA asks applicants to propose two different kinds of activities: 1) novel analyses that are to be developed, proposed, and justified by the applicants within the scope and overall goals of this FOA; and 2) analyses that contribute to the identified cross-program goals of delineating when a common, complex disease study is comprehensive, and providing specifications for a set of common controls for such studies. These two activities may have useful scientific overlap. Because this FOA will fund a component of a larger program, it is important that the proposed work be carried out collaboratively with the other components of the GSP and NHGRI staff.

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.

Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Is it likely that the proposed analyses will add to the characterization of the genomic datasets produced by the GSP? Is it clear how the proposed work will advance the field of analysis of genome sequence and possibly other genome-scale data to improve our ability to characterize sequence variants in the data? Does the application address important questions about, e.g., identifying associations between variants and disease phenotypes; analyses using existing functional data to leverage associations and/or make functional inferences; means to improve study design; and/or other higher level analyses that will add value to the interpretation and characterization of the data produced by the program as a whole, alone or in conjuction with other, existing, genome-scale datasets? Are the methods and principles likely to be generalizable? If the application proposes to generate secondary genomic datasets, will these be of high interest to the community? Does the application propose methods that will advance the two cross-program goals: delineating "comprehensiveness" and providing specifications for common controls?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the investigators have experience in successfully coordinating and collaborating within multi-component complex programs?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Are new analysis methods proposed? Are there novel ideas or approaches e.g., about integrating datasets?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

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?

Does the application overall strike an appropriate and thoughtfully prioritized balance among and between the explicit investigator-driven activities and the program-driven activities?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, 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

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 NHGRI 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 on the basis of established PHS referral guidelines 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 appropriate national Advisory Council or Board. 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.
• Program balance, including establishing a diverse set of analyses.
• 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, including working cooperatively with the GSP Coordinating Center;
• 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:

An NHGRI Project Scientist will have substantial programmatic involvement 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;
• Provide templates for gathering information about progress within the GSP;
• Serve as a liaison between the awardees and the External Scientific Panel, the National Advisory Council for Human Genome Research and the GSPCC;
• 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 GSP;
• 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.

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. The GSP Analysis Centers may be represented individually on the Steering Committee, or NHGRI may choose to have a subset of Analysis Center PIs represent that component. 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 GSP, 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.
• 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.

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Adam Felsenfeld, Ph.D
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: [email protected]

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

Monika Christman
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7860
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.