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 availability of very high-quality human genome sequence assemblies would have a number of benefits. These include an improved ability to resolve structural variants and other structural features that are of high biomedical interest; the resolution of long-range haplotypes to allow understanding of gene and variant interactions based on real haplotypes, including long-range cis regulation; improve our ability to study genes and variants in structurally complex regions of the genome, and provide a more complete set of genes, including ones in heterochromatic regions. Recent technological advances, including direct production of long sequence reads, and reliable efficient methods for synthetic long reads, show high promise to improve the ability to routinely produce higher-quality assemblies, but these methods are still very significantly higher in cost per genome compared to short read assemblies. As the overall assembly quality that is sought approaches haplotype-resolved end-to-end contiguity for each chromosome, the cost becomes very high (by some estimates, over 200X the cost of a short-read assembly). Although routine, cheap, production of such assemblies is not possible today, having even a small (25-50) number of such high-quality genome assemblies, in the short term, would be extremely valuable, particularly for inclusion in genome reference sequences.

The human genome reference sequence (current version: GRCh38; see http://www.ncbi.nlm.nih.gov/projects/genome/assembly/grc/human/) is a very widely used resource for basic and clinical genomics applications. The reference has evolved from the original International Human Genome Project sequence, but still has several shortcomings it contains gaps, it represents structural variation incompletely, it is a mosaic of contributions from multiple individuals, and it mostly does not represent actual haplotypes over long contiguous regions. Moreover, the sequenced samples are not broadly representative of world populations. In the past several years, each of these short-comings has begun to be addressed. This includes the ongoing effort to represent multiple alternate genomic haplotypes as alternate paths in the reference, but this is not comprehensive, and hence investigators often find that an individual genome they have sequenced has some regions that will not map onto the reference. Moreover, producing multiple, high-quality human assemblies is a key step towards a complete account of structural variation.

Separately, NHGRI and others have funded the genomic sequencing of multiple non-human primates (NHP) based on their utility as experimental systems (including disease and drug studies), and also to address basic questions in comparative genomics, including understanding of selection in humans and inferences about ancestral and derived variation. While the quality of the present NHP genome assemblies is sufficient for many applications in comparative genomics, these assemblies generally lag far behind in quality compared to those of human and canonical model organisms. Improving the quality of these genomes to the current level of the human reference, or beyond, is needed to facilitate additional comparative analyses, such as analyses of lineage-specific structural rearrangements and to fully enable the use of these organisms in biomedical research. There are at least a dozen primate genome assemblies that are potentially high priorities (Chimp, Bonobo, Gorilla, Orangutan, Gibbon, Baboon, Rhesus macaque, African Green Monkey/Vervet, Marmoset, Bushbaby, Tarsier, Tree Shrew).

(See http://www.genome.gov/Pages/About/NACHGR/February2015AgendaDocuments/GSP_Feb_2015_Concepts.pdf for the archived Concept for this FOA that was approved by the National Advisory Council on Human Genome Research.)

NHGRI seeks to fund efforts that will produce, as a community resource, very high quality reference genome sequence assemblies in the next three years for human (up to 50 assembles) and select NHPs (10-12), as a complement to and improvement on existing reference assemblies. Applicants may propose work on either human or NHP, or both, within a single application.

For human genomes, the availability of additional very high-quality human assemblies is intended to have significant value for a wide range of significant studies ranging from population genetics, to fundamental studies of genome structure including structural variation, to enabling variant association studies and the ability to analyze individual genomes in clinical applications, especially through the eventual inclusion of the assemblies into the Genome Reference. In addition, this initiative is intended to increase the population diversity represented in high-quality assemblies so that references are more useful for analyses of individual genomes from diverse populations.

This FOA deliberately does not describe a specific required end-point for the quality of the assemblies requested, recognizing that the definition may change with considerations of technology and cost. Instead, some of the current considerations about quality are discussed below. In the course of pursuing the FOA goals, it is expected that awardees of this program will develop more specific scientific and practical definitions of what a very high-quality reference should be, in the context of available and evolving methods and the scientific added value of further quality improvements.

The ultimate quality assembly would be a fully haplotype-resolved genome with complete representation, perfect base accuracy, and chromosome-level contiguity. More realistically, current high-quality genomes, within the present state of the art, have the following general characteristics: all sequence data come from a single individual; a majority of the assembly is haplotype-resolved over long intervals; very high contiguity/quality through multiple (several hundred) specific regions of the genome known to be high in structural variation and significant for human disease. Although this is the state of the art, NHGRI encourages applications that propose efficient generation of even higher quality assemblies, using and adapting technologies that are currently available or will be available in the next three years, and balancing cost and quality

For NHP genomes, this FOA also seeks to develop an endpoint for refined genome assemblies of significantly greater utility than the current assemblies. This end-point may or may not be the same as that for human, but must be based on added scientific utility to achieve goals such as those listed in the Background section balanced against cost. NHGRI requests applications that propose, and justify, work on those species where there is an existing draft assembly and interested community. Although NHGRI has listed priority species in the Background section, applicants may propose different species if well justified.

NHGRI notes that the mammalian Y-chromosome is especially challenging to sequence and assemble. Applications may propose to include the Y-chromosome sequence, but only if it is determined during the course of determining the rest of the genome at a reasonable, incremental cost. Stand-alone applications to sequence and assemble individual Y-chromosomes are not within the scope of this FOA.

For both human and NHP genomes, newer technologies may arise over time that more efficiently generate very high-quality genomes, and it is expected that these will be incorporated into this effort when they are robust, in the context of an integrated production effort to produce a community resource. However, applications should reflect that the demand for higher quality data for basic and clinical applications is immediate, and they must propose to provide the improved genome sequence assemblies within the three-year term of award. Applications should therefore propose integrated data production efforts and are expected to include sequence and other data production related to generating very high quality assemblies, methods refinement to improve quality and decrease costs, and integrated informatics including incremental modification of assembly methods. This FOA will not support extensive, long-term, or stand-alone technology development or informatics, analysis methods or assembly algorithm development.

Finally, it is a goalof this FOA that the resulting genome sequence assemblies be widely and publically sharable as a community resource to advance and accelerate genomic research, for example it must be possible to incorporate the human assemblies into the Human Genome Reference resource. Samples must be consented in a way that allows this. Applications proposing human samples that are not consented for this will be considered unresponsive.

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)
• 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 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.

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, Ph.D
Telephone: 301-496-7531
Fax: 301-480-2770
Email: felsenfa@mail.nih.gov

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: Applications may propose work on either, or both, human and primate genome assemblies in the same application.

Applicants should propose to develop high quality assemblies from up to 50 individual humans and/or 10-12 NHP species. The applicant should state and justify a specific number. Depending on data production costs, and quality considerations, the actual number proposed may be more or less.

Applicants should specify and justify the quality and utility of the products that will be produced with reference to the added value compared to currently available high-quality assemblies. Quality metrics should be clearly stated and justified. Applicants should discuss what internal or external validations of assembly quality will be done.

Applicants should include information on estimated costs (labor, reagents, amortized equipment, not including indirect costs or methods development costs) per high-quality genome, and discuss tradeoffs in the context of how they justify the quality of the proposed product. Applicants should also discuss prospects for cost reduction over the three-year course of the project.

For human assemblies, applicants must justify the diversity of the samples with respect to populations of origin, in the context of improving the current human genome reference sequence and its uses. NHGRI may negotiate population diversity after the award.

For NHP species, applicants must propose and justify species choices based on need for reference improvement, and added scientific value of that species. Applicants should consider the species priorities listed in this FOA, and may suggest, but must justify, alternative or additional NHP species. NHGRI may negotiate species choice after award. Applicants should discuss interactions with communities of investigators with an interest in specific primate species especially those that are intended to result in a product that is of high value to that community.

Applicants should discuss appropriate use and efficient integration of existing sequencing (long reads, synthetic reads, etc.) technologies or those that will be available over the funding period. If incremental methods improvements are proposed, they should be well integrated and clearly linked to the immediate goals of the project. Applicants should describe informatics pipelines that will be used and how they will be integrated and potentially modified to attain goals.

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 they will work with existing community resources that archive or improve genome references. This includes timely submission of assemblies to NCBI, and also--for human--coordination with the Genome Reference Consortium.
• Because it is extremely important that the resulting human assemblies are widely sharable, including being incorporated into public genome references, applicants should discuss how samples are consented for such use.
• 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:

Reviewers should note that this FOA allows applicants to propose work on human, non-human primate, or both. Applicants are expected to propose work on up to 50 human genomes, and or 10-12 NHP genomes, but may propose and justify a different number based on cost and quality considerations.

The work proposed under this FOA may include some elements of incremental methods or informatics development related to producing very high quality genome assemblies. However, because the main purpose of the FOA is to add to the number of very high-quality human and NHP reference assemblies in the short term (next three years) as a community resource the focus is on producing those assemblies quickly.

For the NHP assemblies, NHGRI has indicated a list of high-priority species in the Background section of this FOA. Applicants may suggest, but must justify, alternative or additional NHP species. NHGRI may negotiate species choice after award.

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 work will add significantly to the value of human and/or NHP reference genome sequences within the next three years? Will the availability of the very high quality assemblies be likely to result in new discoveries, e.g., about the structure of genomes, either by the investigators or by the community that will use the resulting resources? For the human assemblies, are sample populations chosen so as to increase the utility of genome references for analysis of diverse populations?

Is the proposed definition of a finished "very high quality" genome assembly likely to be useful for the field as a whole?

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 sequencing, assembling, and making available to the community high-quality genome sequence assemblies? Do they have experience with specialized technologies and approaches to generate very high-quality assemblies?

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 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?

Are the quality and number of the genome assemblies clearly specified and justified with reference to the added value compared to currently available high-quality assemblies? Note that quality considerations may be different for human and NHP sequence assemblies; are these considerations clear? Are quality metrics clearly stated and justified? Are appropriate validations of assembly quality proposed?

Does the application make reasonable tradeoffs between cost and quality in the context of how they justify the quality of the proposed product? Has the applicant proposed ways to maximize quality given the available resources? Are there prospects for cost reduction over the time of the award?

For human assemblies, is the population diversity of the proposed subjects justified in the context of improving the current human genome reference sequence and its uses?

For NHP species, do applicants propose and successfully justify all species choices (included in the list within this FOA, or proposed separately by applicants) based on need for reference improvement, and added scientific value of particular species and/or of the entire set of species? Do applicants propose appropriate interactions with communities of investigators with an interest in specific primate species?

Does the application propose efficient integration of existing sequencing (long reads, synthetic reads, etc.) technologies or those that will be available over the funding period? If incremental methods improvements are proposed, are they well integrated and clearly linked to the immediate goals of the project and the timeline of this FOA?

Does the application propose and describe an adequate informatics pipeline that will be used for e.g., data handling and genome assembly?

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 comment on whether the samples identified are likely to be consented in a way that allows public sharing of the sequence data and incorporation into community resources including genome references.

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, including consent of human samples that will allow public access and incorporation into community resources.
• Program balance, including addressing both the human and the NHP goals of this FOA

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". This is likely to include discussions about selection of particular samples for genome sequencing;

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 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 identified by NHGRI as being an important point of coordination with the activities carried out under this award. This is likely to include other awardees under this program, and the Genome Reference Consortium. This may include interactions with the NHGRI Genome Sequencing Program. This may entail participating in program meetings for the NHGRI Genome Sequencing Program.

Awardees will participate in Steering Committee meetings and conference calls and meetings with any external scientific advisors to the program that may be retained by NHGRI;

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 grantees and NHGRI program staff.

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;

Liaise with the community to identify needs for very high-quality assemblies, including alternate possibilities for specific samples;

Serve as a liaison between the awardees and any external scientific advisors to the program that may be retained by NHGRI, and 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;

Periodically report progress to the Director, NHGRI;

Provide advice on the management and technical performance of the investigation;

Assist in promoting the availability of the genome sequence assemblies and related resources developed in the course of this project to the scientific community at large;

Participate in data analyses, interpretations, and where warranted, may be a co-author on publications;

Participate in Steering Committee meetings and conference calls;

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 this program. The Steering Committee membership will include the NHGRI Project Scientist(s) and one P.I. from each awarded cooperative agreement for this program. 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.

The Steering Committee will:

Meet at least once per year in person or remotely;

Discuss progress in meeting the objectives of the program;

Develop recommendations for uniform procedures and policies necessary to meet the goals of the program, for example for data quality measures and assessments, conventions for data deposition, or measuring costs and throughput;

Serve as a venue for coordination on improvements in very high-quality genome assemblies, 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.

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 Service Desk (Questions regarding ASSIST, 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: commons@od.nih.gov

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-710-0267

Adam Felsenfeld, Ph.D
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: felsenfa@mail.nih.gov

Rudy Pozzatti, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-8739
Email: pozzattr@exchange.nih.gov.

Monika Christman
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-785
Email: christmm@exchange.nih.gov

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.