Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations

National Human Genome Research Institute (NHGRI)

Funding Opportunity Title

Revolutionary Genome Sequencing Technologies – The $1000 Genome (R21)

Activity Code

R21 Exploratory/Developmental Research Grant Award

Announcement Type

Reissue of RFA-HG-10-013

Related Notices

  • October 18, 2013 - See Notice NOT-OD-14-003. Guidance on Resumption of NIH Extramural Activities Following the Recent Lapse in Appropriations.
  • August 21, 2013: Removed reference to ASSIST in section IV.3, since ASSIST is currently only available for multi-project applications.

Funding Opportunity Announcement (FOA) Number


Companion Funding Opportunity

RFA-HG-13-005, R01 Research Project Grant
RFA-HG-13-007, R43/R44 Small Business Innovation Research (SBIR) Grant - Phase I, Phase II, and Fast-Track

Number of Applications

See Section III. 3. Additional Information on Eligibility.

Catalog of Federal Domestic Assistance (CFDA) Number(s)


Funding Opportunity Purpose

The National Human Genome Research Institute (NHGRI) solicits R21 grant applications to develop novel technologies that will enable extremely low-cost, high quality DNA sequencing.  The goal of this initiative is to reduce the cost of sequencing a mammalian-sized genome to approximately $1000.  Applicants may propose to develop full-scale sequencing systems or to investigate challenges underlying key system components.  Exploration of methods other than those currently being pursued as potential $1,000 genome technologies is encouraged.  High-risk/high-payoff applications are appropriate to achieve the goals of this FOA.

Key Dates
Posted Date

June 25, 2013

Open Date (Earliest Submission Date)

September 17, 2013

Letter of Intent Due Date(s)

September 1, 2013

Application Due Date(s)

(Extended to November 1, 2013 per NOT-OD-14-003), Originally October 17, 2013, by 5:00 PM local time of applicant organization.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.

AIDS Application Due Date(s)

Not Applicable

Scientific Merit Review

February-March 2014

Advisory Council Review

May 2014

Earliest Start Date

July 2014

Expiration Date

(Extended to November 2, 2013 per NOT-OD-14-003), Originally October 18, 2013

Due Dates for E.O. 12372

Not Applicable

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.

Table of Contents

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

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description


The National Human Genome Research Institute (NHGRI) solicits R21 grant applications to develop novel technologies that will enable extremely low-cost, high quality DNA sequencing.  This FOA continues a program that began in 2004, when the cost to produce a high quality draft mammalian genome sequence was estimated at $5 to $10 million, and the goal was to reduce costs by four orders of magnitude – to approximately $1,000 – in ten years.

While substantial progress toward the $1,000 genome has been made, daunting scientific and technical challenges remain.  This program will continue to support both fundamental scientific investigation underlying the technologies, and their engineering, to achieve this goal.  The program supports development of key system components and of full systems.  In this context, ‘key components’ refers to the method for determining the linear order of nucleotides, in contrast to upstream or downstream steps in sequencing.  Exploration of methods other than those currently being pursued as potential $1,000 genome technologies is encouraged.  High-risk/high-payoff applications are appropriate to achieve the goals of this FOA.

Parallel FOAs of identical scientific scope (RFA-HG-13-005 and  RFA-HG-13-007) solicit applications under the R01 and Small Business Innovation Research (SBIR) grant programs, respectively.


The ability to sequence complete genomes and the free dissemination of sequence data have dramatically changed the nature of biological and biomedical research.  Sequence and other genomic data have the potential to lead to remarkable improvement in many facets of human life and society, including the understanding, diagnosis, treatment and prevention of disease; advances in agriculture, environmental science and remediation; and our understanding of evolution and ecological systems.

The ability to sequence many genomes completely has been made possible by the enormous reduction of the cost of sequencing in the past 30 years, from tens of dollars per base in the 1980s to a fraction of a cent per base today.  We have progressed from the early Human Genome Project goals to sequence the genomes of the human and mouse and a few additional model organisms (E. coli, C. elegans and D. melanogaster), through programs to sequence at varying pre-determined quality levels numerous genomes across the evolutionary tree including multiple species and variants for some of those, to current programs to sequence portions or the entire genomes of increasing numbers of tumors and human individuals.  Technology advances, and in particular the recent emergence of a new generation of sequencing systems, have enabled the launch of several such projects that are producing stunning insights into biology and disease.  Nevertheless, the cost to completely sequence large numbers of entire genomes remains too high to allow complete genome sequencing to be used routinely, and we remain far from achieving the low costs and high quality needed to enable the use of comprehensive genomic sequence information in individual health care.

A few examples of high priority research to which genomic sequencing at high quality and dramatically reduced cost would make vital contributions include:

The broad utility and high importance of dramatically reducing DNA sequencing costs prompted the NHGRI, in 2004, to embark on two parallel technology development programs (Nature Biotech. 26:1113, 2008).  The first had the objective of reducing the cost of producing a high quality sequence of a mammalian-sized genome by two orders of magnitude, to about $100,000.  This goal has been achieved so no additional grant applications are being solicited at this time. Rather, the NHGRI is focusing its efforts on attaining the goal of the second program, which, as described in this FOA and parallel FOAs for other grant mechanisms, is the development of technologies with which to sequence a human genome for about $1,000 (a four order of magnitude cost reduction).  Implicit in this goal is the quality of the expected sequence product, as sequencing cost targets are meaningless without associated quality standards as described below.

Sequencing Strategy and Quality

The sequencing technology that was used to produce the reference human genome sequence (Nature 431:931, 2004; Nature 409:860, 2001; Science 291:1304, 2001) was fluorescence detection of dideoxynucleotide-terminated DNA extension reactions resolved by capillary array electrophoresis (CAE).  Individual sequence “read” segments can be as long as 1000 nucleotides.  If all of the DNA in a 3 Gb genome were unique, it would be possible to determine the sequence of the entire genome by generating a sufficient number (tens of millions) of randomly-overlapping 1000-base reads and aligning their overlaps.  However, the human and the majority of other interesting genomes contain a substantial amount of repetitive DNA.  To cope with the complexities of repetitive DNA elements and to assemble the thousand-base reads in the correct long-range order across the genome, genomic sequencing methods involve a variety of additional strategies, such as the sequencing of both ends of cloned DNA fragments, use of libraries of cloned fragments of specified lengths, incorporation of map information, achievement of substantial redundancy (multiple reads of each nucleotide from overlapping fragments) and application of sophisticated assembly algorithms to filter and align the reads.  As new sequencing technologies are developed, they must incorporate means to deal with these features of the structure of the genome.

The gold standard for genomic sequencing is based on the above-described methods and remains =99.99% accuracy (not more than one error per 10,000 nucleotides) with essentially no gaps (  The “finishing” steps needed to achieve that very high quality have not been automated and thus require substantial hand-crafting.  However, experience shows that much comparative and medically useful sequence information can be obtained from automatically generated sequence assemblies that are known as “high-quality draft” or “comparative grade.”  Therefore, the cost targets for NHGRI’s sequencing technology development programs were originally defined in terms of a mammalian-sized genome with a sequence quality equivalent to or better than that of the mouse draft assembly published in December 2002 (Nature 420:520, 2002).  Producing such a product for $1,000 is still not possible, so this remains a useful and challenging technology target.  Unquestionably, the ultimate need, for medical research and individualized medicine, is for far higher quality sequence of the 3 Gb diploid human genome.

Subsequent to dideoxy/CAE sequencing, a second generation of sequencing technologies has been developed and implemented.  These are broadly described as array-based methods in which large numbers of templates are extended one base at a time, the extensions are detected, and that cycle is repeated (reviewed in Nature Biotechnology October 2008).  These technologies enable the sequencing of larger numbers of genomes for under $100,000 dollars each, and even less for targeted sequencing of particular genomic regions.  While challenges remain related to producing and interpreting sequence information using these technologies, they are proving invaluable to the biomedical research enterprise and they validate the impetus toward further substantial decreases in cost with increases in quality, throughput and speed of genomic sequencing.

The eventual goal of these programs is to achieve technologies that can produce assembled sequence of genomes that had not been previously sequenced (i.e., de novo sequencing).  However, an accompanying goal is to obtain highly accurate sequence data at the single base level that can be overlain on a reference sequence of the organism (i.e., re-sequencing).  This could be achieved, for example, with short reads that lack information linking them to other reads.  In spite of shortcomings (some of which are described below), re-sequencing would potentially be available sooner and of considerable value for certain studies on disease etiology and individualized medicine.  Therefore, technology development for re-sequencing will be supported under this FOA.  As the cost goal for the more difficult challenge, de novo assembly sequencing, is $1,000, the goal for re-sequencing is to develop technologies that will provide a genome’s worth of less-well-mapped sequence for well below $1,000.

For re-sequencing, the per-base accuracy must be sufficient to distinguish between sequencing errors and real polymorphism.  Additional challenges include assigning reads to gene families with very similar sequence, the identification of copy number changes and genomic rearrangements, and the identification of haplotypes (i.e., linear juxtapositioning of particular single nucleotide polymorphism [SNP] alleles along a single chromosome) in diploid organisms.  Thus, in proposing the development of re-sequencing technologies, it is essential that the applicant clearly address the extent to which the proposed technology will meet or fall short of these various challenges, and the cost tradeoffs that justify developing the technology to produce data of high value for particular biomedical studies.

Specific Areas of Research Interest

The goal of research supported under this FOA is to develop new or improved technology to enable rapid, efficient DNA sequencing of mammalian-sized genomes.  The target cost for a 3 Gb diploid genome sequence determined at reasonably high quality is about $1,000 because the ability to generate routinely complete genomic sequences at that cost would revolutionize biological research and medicine.

Both fundamental scientific discovery and cutting edge engineering will likely be needed to achieve these goals.  For example, new sensing and detection modalities and fabrication methods may be required, and the physics of systems operating at nm length scales will need to be better understood.  It is therefore anticipated that applications responding to this FOA will involve fundamental and engineering research conducted by multidisciplinary teams of investigators.  The guidance for budget requests accommodates the formation of groups having investigators at several institutions, in cases where that is needed to assemble a team of the appropriate balance, breadth and experience.

The scientific and technical challenges inherent in achieving the cost goals are significant. Achieving these goals may require research projects that entail substantial risk.  That risk should be balanced by an outstanding scientific and management plan designed to achieve the very high payoff goals of this FOA.  High-risk/high-payoff projects may fail for legitimate reasons, so applicants proposing such projects should identify them as such, elaborate key quantitative milestones to be achieved, and describe the consequences of not achieving those milestones in a reasonable period of time.

Applicants may propose to develop full-scale sequencing systems or investigate key components of such systems.  For the latter, applicants must describe how the knowledge gained as a result of the proposed project would be incorporated into a full system that they or others might subsequently propose to develop.  Such independent applications are an important path for pursuing novel, high-risk/high-payoff ideas, short of developing a full system.

While the major focus of this program is on the development of new technologies for detection of nucleotide sequence, any successful technology will have to address matters related to the practical implementation of the technologies so that the technology can form the basis of, or be incorporated into, an efficient, high quality, high-throughput DNA sequencing scheme.  Any new technology will eventually need to be incorporated effectively into a sequencing workflow, starting with a biological sample and ending with sequence data of the desired quality.  Sample preparation requirements can depend upon the detection method which, in turn, can affect the way in which output data are handled.  If a full system development is proposed, these issues should be addressed on an appropriate schedule in the research plan; applicants should focus as early as possible in the research plan on the most critical and highest-risk aspects of the project related to determining the sequence of nucleotides, on which the rest of the project depends.  Projects to address key components must address the fundamental method of determining the base sequence (that is, an applicationaddressing only sample prep or only the downstream informatics would not be considered responsive to this FOA).

Most technology developers lack practical experience in high-throughput sequencing and in testing of methods and instruments for robust, routine sequencing operation.  Applicants may therefore wish to include such expertise as they develop their teams.  Academic investigators may wish to consider collaborating with commercial entities that have the experience and capabilities to bring practical systems into the hands of users.

The quality of sequence to be generated by the technology is of paramount importance for this FOA.  Two major factors contributing to genomic sequence quality are per-base accuracy and contiguity of the assembly.  Much of the utility of comparative sequence information will derive from characterization of sequence variation between species, and between individuals of a species.  Therefore, per-base accuracy must be high enough to discern polymorphism at the single-nucleotide level (substitutions, insertions, deletions) and distinguish polymorphism from sequencing errors.  Experience and resulting policy have established a target accuracy of not more than one error per 10,000 bases.  All applications in response to this FOA, whether to develop re-sequencing or de novo sequencing technologies, must propose to achieve at least this standard.

Assembly information is needed for determining sequence of new genomes and ultimately also for genomes for which a reference sequence exists, to detect rearrangements, insertions, deletions, and copy number changes.  All of these are genomic changes that have been shown to be associated with disease, and knowledge of rearrangements can reveal new biological mechanisms.  The phase of single nucleotide polymorphisms to define haplotypes is important in understanding and diagnosing disease.  Achieving a high level of sequence contiguity may be essential to achieve the full benefit from the use of sequencing for individualized medicine, e.g., to evaluate genomic contributions to risk for specific diseases and syndromes, and drug responsiveness.  Nevertheless, it is recognized that perfect sequence assembly from end to end of each chromosome is unlikely to be achievable with most technologies in a fully automated fashion and without adding considerable cost.  Therefore, for the purpose of this FOA, grant applications proposing technology development for de novo sequencing shall describe how they will achieve, for about $1,000, a draft-quality assembly that is at least comparable to that represented by the mouse draft sequence produced by December 2002:  7.7-fold coverage, 6.5-fold coverage in Q20 bases, assembled into 225,000 sequence contigs connected by at least two read-pair links into supercontigs [total of 7,418 supercontigs at least 2 kb long], with N50 length for contigs equal to 24.8 kb and for supercontigs equal to 16.9 Mb (Nature 420:520, 2002).  Grant applications that propose technology development for re-sequencing should fully describe the qualities and characteristics of the genomic sequence information that the technology would produce, and the projected cost.  That cost should be at least four orders of magnitude lower than was the cost to produce comparable quality data in 2004, when this program was initiated.

Grant applications will be evaluated, and funding decisions made, in such a way as to develop a balanced portfolio that has strong potential to develop both robust de novo and re-sequencing technologies, exploring a variety of technology approaches.  If the estimate is correct, that achieving the goal of $1,000 de novo genome sequencing incorporating substantial assembly information will be achieved by about 2014, then low-cost re-sequencing technologies for even lower cost might be expected in a shorter time. Projects with a plan to achieve re-sequencing while on the path to de novo sequencing will receive priority.

Research conducted under this FOA may include development of the computational tools associated with the technology, e.g., to extract sequence information, including image analysis and signal processing, and to evaluate sequence quality and assign confidence scores.  It may also address strategies to assemble the sequence from the information being obtained from the technology or by merging the sequence data with information from parallel technology.  Applications that incorporate effective plans to develop systems that address the bioinformatics challenges in concert with the sequencing wet-ware will receive high priority consideration.  However, this FOA will not support development of sequence assembly or sequence analysis software independent of technology development to obtain the linear nucleotide sequence.

This program is aimed at technology to sequence entire genomes.  Projects are under way to determine sequence from selected important regions (e.g., all of the genes).  Grant applications that propose to meet the cost targets by sequencing only selected regions of a genome will be considered unresponsive to this FOA.  However, applications that propose novel ways to sequence selected genomic regions, cost-effectively, while on a path to whole-genome sequencing, will be considered responsive.

NHGRI is interested in supporting diverse approaches to achieving the goals of this FOA.  To assist the research community, investigators who are pursuing one set of technology paths that involve the use of nanopores and nanogaps published an overview of the challenges they face (Nature Biotech. 26:1146, 2008).  Similarly, challenges attending sequencing by synthesis have been described (Nature Biotech. 27:1013, 2009).  Grant applications to meet these and related challenges, and to pursue alternative technologies, are welcome under this FOA.  Information on projects funded under earlier versions of this and related FOAs and a program bibliography are available at

Section II. Award Information
Funding Instrument

Grant: A support mechanism providing money, property, or both to an eligible entity to carry out an approved project or activity.

Application Types Allowed


The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

NHGRI intends to commit $1 million in FY 2014.  The actual number of awards and amount are contingent upon NIH appropriations and the submission of a sufficient number of meritorious applications.

Award Budget

An application may request direct costs up to $200,000 per year.  Because the nature and scope of the proposed research will vary from application to application, it is anticipated that the size and duration of each award will also vary.  

Award Project Period

The scope of the proposed project should determine the project period.  The maximum project period is 3 years.

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.

Section III. Eligibility Information

1. Eligible Applicants

Eligible Organizations

Higher Education Institutions

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

Nonprofits Other Than Institutions of Higher Education

For-Profit Organizations



Foreign Institutions

Non-domestic (non-U.S.) Entities (Foreign Institutions) are 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.

Required Registrations

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.

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

All PD(s)/PI(s) must have an eRA Commons account and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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.

Eligible Individuals (Program Director/Principal Investigator)

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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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

NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:

Section IV. Application and Submission Information

1. Requesting an Application Package

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

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the SF424 (R&R) Application Guide, 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.

Letter of Intent

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:

The letter of intent should be sent to:

Jeffery A. Schloss, Ph.D.
5635 Fishers Lane
Bethesda, MD 20892-9305
For express delivery use:  5635 Fishers Lane, Rockville, MD 20850
(submission of letters of intent by email is preferred)
Telephone: 301-496-7531

Page Limitations

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

Required and Optional Components

The forms package associated with this FOA includes all applicable components, required and optional. Please note that some components marked optional in the application package are required for submission of applications for this FOA. Follow all instructions in the SF424 (R&R) Application Guide to ensure you complete all appropriate “optional” components.

SF424(R&R) Cover

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

SF424(R&R) Project/Performance Site Locations

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

SF424(R&R) Other Project Information

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

SF424(R&R) Senior/Key Person Profile

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

R&R or Modular Budget

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

Applicants should request travel funds for the PD/PI and two additional lead investigators to attend the annual grantee meetings (see information about these meetings under the heading, Resource Sharing Plan).

Applicants may include funds for an internally appointed advisory board.  However, potential advisors should not be contacted prior to submitting the application, nor should potential advisors be named in the grant application, to avoid conflicts of interest in the review process.

PHS 398 Cover Letter

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

PHS 398 Cover Page Supplement

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

PHS 398 Research Plan

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

Research Strategy: A detailed research strategy should include a description of the level of risk of key technical challenges, alternative approaches, go/no-go decision points, etc. It should also include a detailed timeline accompanied by quantitative milestones (see below) that address the key scientific and technical challenges central to the approach.  The timeline and milestones are essential for use by the grantee and the NHGRI for planning the research project and assessment of progress toward goals, and by the reviewers for evaluating the application.

Timelines and quantitative milestones are essential for development of a realistic research strategy; they provide a basis for project leaders to make decisions, assess their own progress, set priorities, and redistribute resources when needed.  It will be particularly important to establish quantitative milestones in cases where subsequent steps in technology development depend upon threshold performance characteristics of earlier developments.  Elaboration of timelines and milestones is primarily the responsibility of the applicant, and the quality and utility of the proposed timelines and milestones will be a review criterion, because they reflect the insights and judgment of the applicant concerning key challenges and how best to conduct the research.  The NHGRI appreciates that these projects will require research, not just engineering; progress toward milestones will be evaluated accordingly.  If the proposed timeline and milestones are not adequate in the case of an otherwise meritorious application, reviewers of the application may make recommendations to NHGRI regarding improved timelines and milestones.

The applicant's plans to manage risk by managing key project decision points, determining resource re-allocation, project re-direction, etc., should be clearly described as an element of the Research Strategy.  If an internal advisory board is planned, its role in managing project decision points and resource allocation should also be described.

Projects that propose to build sequencing systems (in contrast to developing components) that will be assembled by the end of the project period may wish to present a strong case for that system’s capabilities by proposing to demonstrate the sequencing of a substantial amount of DNA (e.g., mega- to gigabases) at the target cost and quality; other measures may be proposed by the applicant.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the SF424 (R&R) Application Guide, with the following modifications:

To accelerate progress in the field of advanced DNA sequencing technology development, grantees will be required to participate actively and openly in at least one grantee meeting per year.  Substantial information sharing will be required and is a condition of the award; failure to openly share information may be grounds for discontinuation of funding if the goals of the program cannot be met. It is understood that some information developed under the grants will be proprietary and cannot be shared immediately without damaging the commercialization potential of the technology.  Applicants should describe their plans for participating in the grantee meetings and for managing the intellectual property concerns in the context of those meetings and other opportunities for information sharing.  Other investigators in the field (i.e., not supported under this program) may be invited to participate in these workshops; their agreement to share information substantially will be a prerequisite to participation.

Applicants are expected to describe their plan for providing access to the technology developed under this grant support, and information about that technology, consistent with achieving the goals of this program.  For example, the technology might be made available as a fee-for-service, through sale of instruments and/or reagents, through collaboration, through publication and posting of results, plans and methods, or by other means. If any quantity of sequence data will be collected under grant support, it is expected that a plan to disseminate those data  will be described, consistent with achieving the goals of the program.

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

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

Foreign Institutions

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

3. Submission Dates and Times

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, 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 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 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.

4. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

5. Funding Restrictions

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.

6. Other Submission Requirements and Information

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide.

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.

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 by the Center for Scientific Review and responsiveness by NHGRI, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.  

Post-Submission Materials

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-10-115, with the following modifications:  Applicants may submit late-breaking research findings (maximum of 1 printed page) 30 days prior to the review.

Section V. Application Review Information

1. Criteria

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:

The R21 exploratory/developmental grant supports investigation of novel scientific ideas or new model systems, tools, or technologies that have the potential for significant impact on biomedical or biobehavioral research. An R21 grant application need not have extensive background material or preliminary information. Accordingly, reviewers will focus their evaluation on the conceptual framework, the level of innovation, and the potential to significantly advance our knowledge or understanding. Appropriate justification for the proposed work can be provided through literature citations, data from other sources, or, when available, from investigator-generated data. Preliminary data are not required for R21 applications; however, they may be included if available.

Overall Impact

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).

Scored Review Criteria

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?

Does the research plan propose to enable extremely low-cost, rapid, high-quality DNA sequencing?

Are the plans sufficiently bold to constitute a substantial advance, if they can be achieved, toward extremely low-cost, rapid, high-quality DNA sequencing?


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?   


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?

Are key scientific and technological challenges on which the rest of the approach depends, identified and addressed early in the project?

Does the proposed technology address sequence quality and the sequencing of entire genomes?

Does the application clearly state whether the goal is to develop re-sequencing, or de novo sequencing technology, and if the latter, is there an adequate plan for evaluating the achieved long-range contiguity?

Is the analysis of sequencing costs well developed and well-informed, relative to the state of the technology?

Are bold plans counterbalanced to manage the inherent risk, for example by firm theoretical basis, reasonable preliminary data (depending on the mechanism), the track record of the lead investigators, and an outstanding scientific and management plan?

Are the timeline and milestones logical and realistic?

Are key technical barriers and dependencies identified?

Are milestones adequately developed and quantitative, to serve as effective guidance for assessment of progress by the investigators and the NHGRI?

Are plans to participate actively and openly in grantee meetings sufficiently clear and forthcoming so as to contribute substantially to advancement of the field?

If the project involves clinical research, are the plans for 1) protection of human subjects from research risks, and 2) inclusion of minorities and members of both sexes/genders, as well as the inclusion of children, justified in terms of the scientific goals and research strategy proposed?  


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?   

Additional Review Criteria

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.

Protections for Human Subjects

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 Human Subjects Protection and Inclusion Guidelines.

Inclusion of Women, Minorities, and Children 

When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. For additional information on review of the Inclusion section, please refer to the Human Subjects Protection and Inclusion Guidelines.

Vertebrate Animals

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.


For Resubmissions, the committee will evaluate the application as now presented, taking into consideration the responses to comments from the previous scientific review group and changes made to the project.


Not Applicable


For Revisions, the committee will consider the appropriateness of the proposed expansion of the scope of the project. If the Revision application relates to a specific line of investigation presented in the original application that was not recommended for approval by the committee, then the committee will consider whether the responses to comments from the previous scientific review group are adequate and whether substantial changes are clearly evident.

Additional Review Considerations

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.

Applications from Foreign Organizations

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

Select Agent Research

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).

Resource Sharing Plans

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) Genome Wide Association Studies (GWAS).

Budget and Period of Support

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

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the 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:

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:

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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 the DUNS, SAM Registration, and Transparency Act requirements as noted on the Award Conditions and Information for NIH Grants website.

2. Administrative and National Policy Requirements

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

Not Applicable

3. Reporting

When multiple years are involved, awardees will be required to submit the annual Non-Competing Progress Report (PHS 2590 or RPPR) 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 on all subawards over $25,000.  See the NIH Grants Policy Statement for additional information on this reporting requirement. 

Section VII. Agency Contacts

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

Application Submission Contacts

eRA Commons Help Desk (Questions regarding eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Web ticketing system:
TTY: 301-451-5939
Email: Customer Support (Questions regarding registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Web ticketing system:

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone: 301-435-0714
TTY 301-451-5936

Scientific/Research Contact(s)

Jeffery A. Schloss, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531

Peer Review Contact(s)

Ken Nakamura, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-402-0838

Financial/Grants Management Contact(s)

Cheryl Chick
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858

Section VIII. Other Information

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.

Authority and Regulations

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 Parts 74 and 92.

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