Department of Health and Human Services

Part 1. Overview Information
Participating Organization(s)

National Institutes of Health (NIH)

Components of Participating Organizations


Funding Opportunity Title

Genome Sequencing and Analysis Centers (U54)

Activity Code

U54 Specialized Center - Cooperative Agreements

Announcement Type

This is a re-issue of RFA-HG-06-001

Related Notices

  • January 28, 2011 - See Notice NOT-HG-11-012 The purpose of this Notice is to modify the information in the FOA regarding permitted cost caps.
  • January 20, 2011 - See Notice NOT-HG-11-011 The purpose of this Notice is to correct the fiscal year in Part 2: Section II Award Information.
  • January 11, 2011 - See Notice NOT-HG-11-010 Notice to remind potential applicants who plan to submit applications in response to this FOA that they are also required to submit companion applications that encourage diversity training using the funding opportunity announcement: Initiative to Maximize Research Education in Genomics (R25) PAR-09-245.
  • December 21, 2010 - See Notice NOT-HG-11-007 Information Teleconference and Webinar for Applications to NHGRI Sequencing and Ethical, Legal, and Social Implications (ELSI) FOAs.

Funding Opportunity Announcement (FOA) Number


Companion FOA

PAR-09-245; see Initiative to Maximize Research Education in Genomics (R25);

RFA-HG-10-016; RFA-HG-10-018; RFA-HG-10-019

Number of Applications

Only one application per institution is allowed Section III. 3. Additional Information on Eligibility.

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


FOA Purpose

This solicitation seeks renewal of the National Human Genome Research Institute’s large-scale sequencing program. This program has successfully completed the human genome sequence and the genomic sequences of many organisms of importance for biomedical research and comparative genomics, characterized detailed genetic variation in human populations, and initiated many medical sequencing projects to identify genomic changes implicated in inherited disease and cancer. NHGRI intends to renew its large-scale sequencing program, continuing its record of increasing production and decreasing costs over time, which will allow application of high throughput sequencing to increasingly challenging questions, for example the basis for complex inherited disease. The program will continue its emphasis contributing to understanding the underlying role that DNA-based changes contribute to biological systems. The renewed program will also emphasize the increasingly challenging issue of identifying and designing new project types that address the most compelling new questions that can be answered as high throughput sequencing continues to evolve, and also the increasingly challenging bioinformatics and integration issues that attend such studies. During the next four years, NHGRI anticipates that the type and number of important large-scale sequencing products will continue to expand, requiring new flexibility from the components of the program. Applicants to this program are required to submit a parallel application to the Initiative to Maximize Research Education in Genomics (R25)

Key Dates
Posted Date
Open Date (Earliest Submission Date)

Not Applicable

Letter of Intent Due Date

February 3, 2011

Application Due Date(s)

March 3, 2011

AIDS Application Due Date(s)

Not applicable

Scientific Merit Review

July, 2011

Advisory Council Review

October, 2011

Earliest Start Date(s)

December, 2011

Expiration Date

March 4, 2011

Due Dates for E.O. 12372

Not Applicable

Required Application Instructions

It is critical that applicants follow the instructions in the PHS398 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. While some links are provided, 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 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

Nature of Research Opportunity and Background. This solicitation seeks applications for support of genomic sequencing and analysis centers, which will constitute the renewal of the NHGRI large-scale sequencing program. In the last five years the NHGRI’s large-scale sequencing program (for a program description see has made major contributions to a broad range of activities and biomedical questions that can be addressed by high-throughput sequencing, including:

This range of activities was enabled over the last four years by startlingly rapid increases in sequencing efficiency and throughput, enabled by next generation sequencing platforms. In the last four years the annual throughput of the NHGRI program rose from 150 Gbases to over 35,000 Gbases, under roughly constant levels of funding (~$120M per year).

In addition to marked increases in efficiency of data production, at least three other factors were essential to the success of the program:

Project design: Increased understanding about how to apply sequencing capacity to a range of important biomedical problems, including cancer and complex disease studies.

Data analysis: Increased understanding about how to analyze sequence data in new project types, for example to find well-validated variants associated with phenotypes.

Together with the above, development of informatics including infrastructure and software tools required for analysis, from LIMS systems to tools for basecalling, sequence alignment, identification of variants and analysis of metagenomic data.

Thus, over the last five years, the useful outputs of the large-scale sequencing program--from project designs through sequence production and data analysis--have broadened, become more integrated, and their value has increased for addressing significant biomedical questions. NHGRI expects that this trend will continue in the next four years, across a similarly broad range of applications, though concentrating largely on the identification of genomic changes implicated in heritable disease and the elucidation of the genetic changes associated with cancer.

Another development over the last five years is that many more scientific groups outside the large centers have access to significant sequencing capacity, both because of the demonstrated value of sequence data, and the increased capacity of the newer sequencing platforms. This places additional importance on the idea that the NHGRI program must continue to improve and define the state-of-the-art in both data production and in what can be called sequencing know-how the development of project designs, analysis methods and tools, which can then be disseminated to the wider community that is increasingly undertaking sequencing projects at all scales.

Scientific Knowledge to be Achieved. This discussion highlights what NHGRI seeks in its renewal of the large-scale sequencing program:

Each of these will be discussed in detail below.

Sequencing Project Target Selection. During the past five years, the specific sequencing targets addressed by the NHGRI program have been chosen in several ways. Initially, organismal targets and some medical sequencing targets were recommended to the NHGRI and the National Advisory Council for Human Genome Research (NACHGR) by working groups composed of members of the research community. However, as sequencing capacity and analysis capabilities grew, this mechanism was not optimal considering the rate of change in sequencing and the new types of project and project designs that were thus becoming possible, and to foster collaborations, sometimes including additional funds, with other NIH institutes. As a result, additional mechanisms were required to identify compelling new projects that were appropriate for the program capabilities. For example, The Cancer Genome Atlas ( was conceived of as a collaboration between NHGRI and the National Cancer Institute, with subsequent sequencing project design carried out by project working groups, with ongoing management in order to ensure that the project design evolved together with the technology. Similar collaborations include a medical sequencing project on autism developed with the National Institutes of Mental Health (NIMH), with NIMH providing funding (through the American Recovery and Reinvestment Act) to peer-reviewed applications, and NHGRI providing genome sequencing capacity; the Human Microbiome Project, a trans NIH project supported by the NIH Common Fund and NHGRI’s sequencing program, proposed by program and approved by the NIH centrally and medical sequencing projects identified through a collaboration with the Genes, Environment and Health Initiative (GEI), again with GEI using peer review to identify projects and NHGRI providing matching sequencing capacity. The 1000 Genomes project ( was identified, and an initial design proposed by international collaborators including NHGRI, at a joint workshop held in 2007; the concept was approved at NHGRI in consultation with the NACHGR. As with other large projects, 1000 Genomes requires ongoing project management and a project design that evolves with improving technology and analysis results. Finally, during the last award period, NHGRI provided for Center Initiated Projects (CIP s) in which the sequencing centers themselves identified projects. These projects generally are expected to be scientifically compelling, unlikely to be identified through other available means, and are intended to encourage and test state-of-the-art applications (new technologies, analyses, designs, etc.). CIPs are reviewed by NHGRI staff, in conjunction with the Scientific Advisory Panel for the sequencing program cooperative agreements (see Section VI.2 of this document). In the next award period, NHGRI expects to continue to require this variety of mechanisms for selecting new sequencing targets, given the new compelling scientific opportunities, the need for developing sequence resources to serve the broad interests of the NIH community, the range of different project types, designs, and scales, and the continuing rapid evolution of sequencing technology. NHGRI remains committed to undertaking high-quality projects proposed by communities of investigators, so these target selection mechanisms will include a community-driven component.

Development of this FOA was informed by discussions raised at an Institute-sponsored workshop on the future of genomic sequencing, (see, by the National Council for Human Genome Research, and by other scientists involved in the NHGRI sequencing program (both current grantees and advisors). These considerations were also discussed in the context on NHGRI’s current panning process ( It is important to note that the resulting recommendations included soliciting a renewal of the NHGRI large-scale sequencing program, but also encouraged the creation of smaller sequencing centers focused on specific questions to take increased advantage of the dispersal of sequencing capabilities and community creativity; and the development of sequencing informatics tools and infrastructure to further the use of sequence data in many settings. Solicitations addressing these recommendations will be released at the same time as this FOA (please see RFA-HG-10-016 Mendelian Disease Sequencing Center; RFA-HG-10-017 Clinical Sequencing Exploration Centers; and RFA-HG-10-018 and RFA-HG-10-019 Informatics Tools for High-Throughput Sequence Data Analysis).

Objectives. This FOA seeks applications for research applicationapplications to implement genome sequencing centers that maintain and extend the state of the art for high throughput, low cost genomic sequence data. However, excellence in producing high quality whole genome shotgun sequence data in a highly efficient manner, while a requirement, will not be sufficient for receipt of an award as an NHGRI genome sequencing and analysis center in the next project period. Two additional features are required. First, centers must be scientifically flexible and creative enough to identify, design, and carry out a wide variety of sequencing projects, from those of established design and of compelling scientific importance, to those that develop novel applications of sequencing enabled by new technologies and methods. Moreover, the flexibility must extend to many different types of biomedical questions of broad interest to NIH, including medical sequencing and organismal sequencing. Second, NHGRI intends that the participants in the sequencing program contribute deliverables beyond production of data and community resource projects, for example the program must identify and address highly significant biomedical questions that can be informed by high-throughput sequence data, and provide sequencing know-how to the community in the form of knowledge about how to design a project, analysis methods and tools, and informatics tools for sequencing thus serving as intellectual resources in this critical area for the scientific community, and to stimulate further the adoption of high-throughput sequence approaches in the wider community.

State-of-the-art, flexible genome sequencing centers. A cardinal accomplishment of the NHGRI large-scale sequencing program has been the substantial improvement in the state of the art for large-scale sequencing. In responding to this FOA, the applicant should provide plans for how s/he will continue to drive the state of the art and continue to obtain gains in the efficiency of genomic and other sequencing. In setting technology improvement as a continuing goal of the program, NHGRI recognizes that the renewal of its genomic sequencing program comes at a time when several different sequencing platforms are operating at scale in production pipelines. It is clear that still other technologies will be tested, and some adopted, during the next four years. Experience shows that introduction of new technologies, while providing a benefit, entails significant challenges, including implementing the new platforms in production, understanding the characteristics and best uses of the data, and integration into the pipeline, from sample preparation through analysis of data and validation (including considerable changes to informatics pipelines). In renewing the sequencing program, NHGRI intends to provide adequate funding to encourage sequencing centers to explore further development of the present technologies, and, as appropriate, adoption of the new technologies. Therefore, the applicant should discuss how the center will remain at the state of the art across multiple different project types, how center activities will improve existing platforms and/or adopt new technologies, and what considerations are critical in deciding to use a specific platform or mix of platforms for different project types likely to be done over the award period. As part of this discussion, the applicant should address his/her past record of technology development and implementation, including experience in implementing new sequencing platforms.

Continuing gains in efficiency. The applicant should also include a discussion of how sequencing costs and data characteristics can be expected to change over the term of the award, in the context of what kinds of projects can be undertaken, and how they will affect projects that are already ongoing. If realized, cost decreases will undoubtedly lead to changes in the scientific opportunities afforded by sequence data. Projects once seen as important but too expensive will become reasonable, and entirely new kinds of highly significant projects will become possible. Such changes will be reflected in the targets addressed by the NHGRI sequencing program over time. Applicants should discuss cost and other improvements in relation to the range of project types currently underway within the NHGRI program e.g., medical sequencing to elucidate the basis for inherited disease; cancer genome sequencing; cataloging variation; metagenomic sequencing; organismal sequencing; non-genomic (RNA, epigenomic) sequencing--- with reference to ongoing projects that are good examples of appropriate use of capacity, project design, and compelling science. In addition to currently feasible project types, applicants to this FOA are expected to contribute to identifying these new opportunities, and should discuss continuing gains in efficiency in relation to what new questions and project designs are likely to present themselves in the next four years.

The ability to conceive of, design, and carry out well-justified, highly significant, and integrated projects. Applicants must provide evidence for their ability to undertake sequencing projects across the broad range of current NHGRI interests. Applicants should discuss the full range of activities associated with a project, for example from sample acquisition, sample preparation, sequencing, initial analysis, validation, data deposition, and interaction with the relevant communities. While most of the future emphasis will be on medical and cancer sequencing, NHGRI expects activities to continue across a range of topics, including:

Medical sequencing. Finding sequence variants that underlie inherited diseases. NHGRI is currently engaged in multiple medical sequencing projects in both Mendelian and complex disease, ranging from deep sequencing of small numbers of loci, to whole exome sequencing, to whole genome sequencing. For some projects, designs may include sequencing to understand transcriptomes or epigenomes. As capacity and analysis capabilities improve, these projects will become more numerous and ambitious. Medical sequencing may also extend beyond understanding disease phenotypes, to phenotypes generally related to health.

Cancer sequencing. The highest profile NHGRI efforts in cancer sequencing have been in conjunction with TCGA. It is anticipated that cancer sequencing will continue, both as part of the TCGA effort to participate in a comprehensive survey of cancer types, and to explore cohorts/samples in that can address more detailed questions (for example resistance to treatment or relapse; surveying transcriptomes).

Cataloguing human variation. The 1000 Genomes project will be largely completed by the start of the term of award of this FOA, yet much work remains to be done, either in exploring rarer variation, or in expanding the number of populations that are sampled. NHGRI is likely to be significantly involved in cataloguing human variation in the future. In addition to making comprehensive catalogues to aid interpretation of medical sequencing studies, understanding human variation is also essential to understanding of many basic issues in population genetics of relevance to human health, including recent adaptations in human populations (in response e.g. to climate, geography, diet, and pathogens).

Metagenomic sequencing of the human microbiome: The Human Microbiome Program will complete its five year term as a trans-NIH and NHGRI supported project in FY 13. The HMP is of finite scope but there remain many other interesting approaches possible, such as: improving the catalog of human microbes, exploring changes in the human microbiome under numerous environmental and medical conditions, correlating human microbiome content with the human genotype, etc.

Organismal sequencing. Notably, the new short read sequencing platforms have not been as successful for whole genome assembly projects for large genomes, as they have for re-sequencing projects over the last five years. Thus the need for improvements in organismal sequencing remains. Compelling projects are likely to arise in any one of the following areas:

Comparative sequencing has been shown to be one of the most efficient and powerful means to delineate important functional features in genomes (including our own) and to provide insight into major biological innovations. While much has been accomplished, a great deal remains to be learned. For example, it would be very attractive to sequence the primate lineage in more detail, in order to identify lineage-specific elements and to highlight the genomic differences between ourselves and our closest relatives. In addition, we do not yet have a sufficient amount of comparative data to reliably delineate all of the conserved functional elements in the human genome---including cis-regulatory sequences, microRNA genes and target sites, splice enhancers/inhibitors, constrained regions of proteins, and others---to the desired resolution. Comparative genome sequencing can also help inform our understanding of how genomes evolve, including understanding of genome duplication, evolution of gene regulatory pathways, and speciation.

Basic knowledge in population genetics to inform understanding of human population genetics, including the genomic basis for rapid adaptation within populations.

Eukaryotic pathogen and vector genomes. NHGRI plans to continue to devote a portion of its sequencing capacity to additional human pathogens and vectors.

New model systems. While many of the major model systems have been sequenced, NHGRI is still approached by model organism communities about sequencing the genomes of the organisms that they are studying.

In addition to demonstrating an ability to carry out projects of the kind that are currently underway, applicants should propose new areas, and/or new or significantly modified approaches to current project types (see Target Selection and Prioritization, below). These ideally should be well-justified, highly significant, integrated projects that take best advantage of high-throughput sequencing to answer important biomedical questions, and which will be examples of types of sequencing project that are likely to be widely undertaken.

Target selection and Prioritization. New sequencing targets will be added over the course of the award period. Overall and long-term priorities will be determined by the NACHGR and NHGRI staff. As discussed above, NHGRI anticipates that it will use a range of mechanisms to approve and prioritize specific sequencing projects within center pipelines, including NHGRI-initiated projects and collaborations with other institutes and other funding agencies, including international collaborations, projects proposed by the community to be approved by a number of mechanisms including standing working groups, and center-initiated projects approved by NHGRI staff in conjunction with the Scientific Advisors to the program. Applicants are expected to identify initial center-initiated projects in their applications, which should, in combination with any ongoing NHGRI-funded projects, occupy the first twelve to eighteen months of anticipated center capacity. This FOA does not limit the capacity that may be devoted to center-initiated projects. However, NHGRI anticipates that at least 50% of program capacity will be required for NHGRI- and community initiated projects over the course of the award period, and will prioritize those projects. The target selection mechanisms will be evaluated on an ongoing basis by NHGRI, the Sequencing Advisory Panel (SAP), and the NACHGR, and modified if warranted.

Note on ongoing projects/maintenance of NHGRI sequencing resources. Successful grantees will be expected to contribute to ongoing NHGRI projects that will not be completed by the time of the new award, including for example completing NHGRI commitments for ongoing improvements in organismal reference sequences. One important NHGRI activity is its participation in the Genome Reference Consortium ( Applicants may request funds for this activity (and must then include a discussion of activities to be carried out), but only a single applicant will receive funds for it.

The ability to analyze data from these projects. Applicants should discuss their analysis pipelines, including plans for how analysis methods and tools will keep pace with changes in sequencing throughput increases, new technologies and new projects types or designs. Analysis is meant here in its broadest sense, to include e.g., validations and/or the ability to productively interact or collaborate with the scientific community that may have specific expertise in, for example, organismal biology, metagenomics or population genetics, in order to maximize the contribution of the sequence data produced by the centers.

Provide leadership. As stated above, NHGRI intends to expand the explicit deliverables of the program beyond the production of sequence datasets to include the dissemination of sequencing know-how , including recognizing compelling new applications for large-scale sequencing, developing new project designs and analysis methods that will be generally useful for additional studies of the same type, and developing informatics tools for, e.g., medical sequencing. Applicants should therefore discuss their past record in this regard and how their center will contribute to these deliverables. More generally, applications will be judged in part on the likelihood that the resulting centers will be community leaders in sequence-based biomedical studies, during a time when sequencing expertise and capacity is likely to become more dispersed, and to be applied to many new projects at many scales.

In summary, this solicitation seeks applications for genome sequencing and analysis centers that will operate at and extend the state of the art of large-scale genomic sequencing with respect to cost, throughput, and quality, and which will contribute significantly to addressing the many questions where high-throughput sequence data is essential. The successful applicant will have a proven track record for producing high quality genome projects. As guidance in preparing an application, NHGRI considers the current state of the art for a genome sequencing centers to encompass most or all of the following:

In addition to maintaining and defining state-of-the-art capability, this FOA seeks applications for centers that will be flexible enough to be rapidly responsive to the new scientific and technological opportunities discussed above. Fundamentally, this solicitation seeks large-scale sequencing centers that can address the most important scientific opportunities, while consistently improving the state-of-the-art in all production areas. Beyond sequence production, this FOA seeks centers that can contribute to sequencing know how for example by identifying the most compelling projects that are appropriate for high-throughput sequencing and which will be examples of project types likely to be useful to many investigators, by developing useful analysis methods and sequence informatics tools, and finally by addressing compelling questions in all of the areas discussed in this solicitation, including cancer and complex disease genetics, metagenomics and organismal biology.

Training Objectives: Diversity Action Plan (DAP). Applicants to the large-scale sequencing program are required to submit a parallel application to the Initiative to Maximize Research Education in Genomics (R25) There is abundant evidence that the biomedical and educational enterprise will directly benefit from broader inclusion of groups traditionally under-represented in genomic research. Recent studies have supported the argument that diversity enhances the quality of education in multiple settings. Studies have suggested that racially and culturally concordant scientific staff may be more successful in recruiting individuals from minority groups into clinical trials. Racially similar physician-patient dyads also may be related to greater patient satisfaction in ways that could enhance communication and participation in clinical research settings. There is no question that the need for a diverse workforce permeates all aspects of the nation's health-related research effort.

The very nature of genome and ELSI research demands the inclusion of a diversity of points of view and scientific interests. One of the major emphases of genomics is to investigate how DNA sequence variation affects phenotypic differences, especially differences in susceptibility to disease among various groups. The significant societal ramifications of this research will also need to be addressed. It is clearly desirable to have individuals involved who bring diverse perspectives to this research, including an interest in understanding diseases that disproportionately affect medically underserved populations. Genome research will affect all populations and thus all groups need to participate in setting the research agenda and examining the broader issues raised by it.

The NHGRI wants to ensure that the next generation of genome scientists will have representation from populations that are currently underrepresented in genomic science as researchers in genomic science, including American Indian or Alaska Native, Black or African American; Hispanic or Latino; Native Hawaiian or Other Pacific Islander, individuals with disabilities, and individuals from disadvantaged backgrounds. The large-scale sequencing program is among the initiatives that have been identified as preferred incubators for research education and training in genomics. Initiatives targeted to those at the undergraduate level and/or beyond, including the faculty level, are encouraged and will be given the highest priority. The main focus should be on ensuring that individuals: (a) successfully transition to the next career level; (b) remain in a science, technology, engineering, and mathematics (STEM) field; (c) pursue doctoral degrees or advanced training in fields relevant to genomics; and (d) pursue careers in genomics. Examples of how these objectives can be accomplished include, but are not limited to, academic enhancement programs, appropriate laboratory experience; mentoring adequate for the career level; career development activities; enhancements in writing scientific papers and fellowship/grant applications; and developing scientific presentation and interviewing skills. The duration of the research education and training program must coincide with that of the parent grant application.

The types of research experiences that can be supported under this award include, but are not limited to: (1) short-term research experiences for undergraduate and graduate students; (2) up to two years of post baccalaureate research and academic support with the objective of transitioning to a F31 support for graduate school; (3) up to 24 months of graduate school support with the objective of transitioning to a F31; (4) up to 24 months of postdoctoral fellowship support with the objective of transitioning to a F32; and (5) research experiences for faculty to provide preliminary data for research grant applications. Exceptions to accommodate research experiences for high school students will only be made for competing continuations of the parent grant that have in the past supported such students. In such cases, support of high school students must represent less than 10 percent of total support requested.

The proposed research education and training initiative may complement other ongoing research training and education programs at the applicant institution, but the proposed educational experiences must be distinct from those research training and research education programs currently receiving federal support and provide added value. The R25 is not a substitute for an institutional research training program (T32) and cannot be used to circumvent or supplement Ruth L. Kirschstein National Research Service Award (NRSA) mechanisms.

The NIH encourages all proposed programs to foster the participation of individuals from racial and ethnic groups underrepresented in biomedical and behavioral research, individuals from disadvantaged backgrounds, and individuals with disabilities.

Awards for this FOA will not be made in the absence of a DAP program. If your institution already has a Diversity Action Plan that is funded through NHGRI, contact program staff listed in this FOA.

Data and Resource Release. NHGRI strongly endorses rapid release of genomic data and materials. Applications submitted in response to this FOA should include a plan for data release, and plans for disseminating informatics tools that will be developed. The NHGRI policy on release of sequence data is available at The purpose of this FOA is to fund genome sequencing centers that will produce large amounts of DNA sequence data. The utility of the data is largely dependent on how quickly they can be deposited into public databases for use by the scientific community. NHGRI considers its large-scale genomic sequencing program to be a community resource project as discussed in the report Sharing Data From Large-Scale Biological Research Projects - 2003: A System of Tripartite Responsibility available at Because some of the medical sequencing information that would be produced through projects as described in this FOA could raise issues about patient confidentiality, it may be appropriate for some medical sequencing information to be released with certain safeguards of confidentiality. NHGRI has developed policies for such data release ( Applicants should discuss data release in the context of these policies. NHGRI deposition policies evolve with time. Currently, NHGRI is developing policies regarding the specific data to be released from short-read sequencing technologies, and policies regarding public notification about individual sequencing projects and terms of use of data from those projects. Applicants should check for updates that may occur during the time this FOA is being competed. All successful applicants will be expected to abide by policies during the award period.

Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (

See Section IV.2 Content and Form of Application Submission Other Submission for specific discussion about what should be included in the application.

Section II. Award Information
Funding Instrument

Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, scientific or program staff will assist, guide, coordinate, or participate in project activities.

Application Types Allowed

The OER Glossary and the PHS398 Application Guide provide details on these application types.

Funds Available and Anticipated Number of Awards

The following NIH components intend to commit the following amounts in FY 2011:
NHGRI; at least $90 M/year; up to three awards anticipated

Award Budget

Individual application budgets should not exceed $45M per year, direct costs and must reflect actual needs of proposed project.

Award Project Period

The total award period requested for this FOA may not exceed four 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



Non-domestic (non-U.S.) Entities (Foreign Organizations) are not eligible to apply. Foreign (non-U.S.) components of U.S. Organizations are not allowed.

Required Registrations

Applicant organizations must complete the following registrations as described in the PHS398 Application Guide to be eligible to apply for or receive an award. Applicants must have a valid Dun and Bradstreet Universal Numbering System (DUNS) number in order to begin each of the following registrations.

All Program Directors/Principal Investigators (PD/PIs) must also work with their institutional officials to register with the eRA Commons or ensure their existing eRA Commons account is affiliated with the eRA Commons account of the applicant organization.

All registrations must be completed by the application due date. Applicant organizations are strongly encouraged to start the registration process at least four (4) weeks prior to the application due date.

Eligible Individuals (Project Director/Principal Investigator)

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Project Director/Principal Investigator (PD/PI) 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 PHS398 Application Guide.

The lead Principal Investigator must devote at least 3.6 person/months, based on a 12-month calendar to this Cooperative Agreement.

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

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

NIH will not accept any application in response to this FOA that is essentially the same as one currently pending initial peer review unless the applicant withdraws the pending application. NIH will not accept any application that is essentially the same as one already reviewed.

Section IV. Application and Submission Information

1. Address to Request Application Package

Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.

2. Content and Form of Application Submission

It is critical that applicants follow the instructions in the PHS398 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.

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:

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

The letter of intent should be sent to:

Adam L. Felsenfeld, Ph.D.
Program Director, Large-Scale Sequencing
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892
Telephone: 301-496-7531

Application Submission

Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and three signed photocopies in one package to:

Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)

At the time of submission, two additional paper copies of the application and all copies of the appendix files must be sent to:

Rudy Pozzatti, Ph.D.
Office of Scientific Review
National Human Genome Research Institute
5635 Fishers Lane
Suite 4076, MSC 9305
Bethesda, MD 20892
Telephone: (301) 496-7531

Page Limitations

All page limitations described in the PHS398 Application Guide must be followed, with the following exceptions or additional requirements:

Research Plan

All instructions in the PHS398 Application Guide must be followed, with the following additional instructions:

The NHGRI has conducted several competitions for large-scale projects and it has been our experience that there are specific information items and presentation formats that the reviewers have found to be critical for their ability to assess applications for such efforts effectively. The following guidance summarizes that experience in the form of a format that the applicant may use to provide that information. If there is additional information, not addressed in this Guidance, that the applicant wishes to present, s/he is encouraged to provide it in a concise form, in addition to the information requested here.

Applications in response to this FOA should include three Research Plan sections: I. Overall Center Management Plan (30 pages); II. Large-Scale Sequencing plan (30 pages); III: Center Initiated Projects.

I. Overall Center Management Plan

This section (30 pages maximum) should contain an extensive Progress Report including an introduction and rationale, and also retrospective information about the investigator’s track record in large-scale sequencing, as detailed below. It should also include a proposal and plan for overall center management, decision-making, coordination, management of collaborations, etc.

I.1 Progress Report. The progress report should represent the applicant's past accomplishments, rather than future plans. Brief, concise summaries are encouraged, and the total length of this section must not exceed 20 pages. The Progress Report should address each of the factors discussed in the RESEARCH OBJECTIVES section above, and should include the following:

I.1.a. General introduction and justification. One important aspect of the NHGRI sequencing program has been how it has advanced biomedical knowledge. Therefore, the application should include a brief discussion of how the applicant’s sequencing work has contributed to the advancement of biology and medicine. The track record in outreach to the community using the sequence information generated should be discussed. If the applicant has participated as part of the NHGRI Research Network, or another collaborative research group, efforts to facilitate the success of that larger group should be described.

I.1.b. Genome sequencing. The applicant should include in the progress report a concise description of past experience in large-scale sequencing and describe any relevant sequencing products, including directed sequencing datasets, whole exome and whole genome shotgun data sets, whole genome shotgun assemblies, directed sequencing data sets, refined or finished genome sequence data sets, transcriptome data sets, and so on. Past experience should be related explicitly to the description of the state of the art in large-scale sequencing as discussed in the Research Objectives section above. Each of the following factors should be addressed (the applicant may change the order of the presentation):

Identification and Design of projects that are novel and/or significant applications of large scale sequencing. The applicant should discuss his/her accomplishments relating to the identification, design, implementation, and completion of significant sequence-based projects appropriate to and that are examples of the contemporary state of the art in large-scale sequencing.

Throughput and production costs. Applicants must provide throughput and cost information. In presenting the quantitative cost and throughput information requested in this section, the applicant may choose, but is not required, to use the suggested production throughput and cost reporting table entitled available at to report retrospective production and cost data. This suggested table may be used for the convenience of the applicant; its purpose is to facilitate a uniform summary of the information from applicants to ensure equitable review. Whether or not the specific table is used, applicants should include all information described below in reporting throughput and cost.

All throughput and cost information should be provided for the most recent three-month period or quarter. All modes of high-throughput sequencing should be included (that is, whole genome or exome resequencing, metagenomic, epigenomic, RNA sequencing except as specified for whole genome and whole exome sequencing, where only human resequencing should be considered).

i. Production & Quality Metrics

ii. Production costs

Other sequencing activities not covered above, and that are relevant to proposed activities. Include e.g. de novo sequencing/assembly, finishing/refinement, clone-based sequencing. Capacity and recent costs (as discussed above) should be discussed.

Assessment of quality of various sequencing products. The applicant should describe how the quality of each of the sequencing products that have been produced has been measured or assessed.

Prior experience in attaining production milestones. The applicant should discuss his/her track record in attaining production milestones.

Informatics. The applicant should discuss his/her experience with all aspects of informatics related to the production aspects of large-scale sequencing, including basic IT infrastructure, laboratory information management (LIMS), and data handling and deposition. Applicants should also discuss experience with informatics and software development related to analysis of sequence data, including analysis of medical sequencing data, base calling, read mapping, variant calling, genome assembly, automated annotation, etc. Discussion should include the successful adoption, if any, by groups outside the center.

Technology Development. The applicant should address any experience that s/he has had in developing and improving technology for large-scale sequencing, especially in integrating new sequencing platforms. The discussion should describe, in quantitative terms, the effect that such technology improvements have had in process improvement and decreased production costs.

Outreach and dissemination. The applicant should address past experience in collaborating with individual research communities on specific genome projects. Of particular interest is experience in dissemination of knowledge about how to use the genome sequence , and the scientific outcomes of those collaborative relationships. Applicants should also discuss how any project design principles that they developed have been taken up or extended by the community.

I.2 The Overall Center Management Plan Proposal. The P.I. of a large-scale project funded under this FOA is expected to devote at least 3.6 person/months, based on a 12-month calendar (equivalent to 30% of his/her time and effort) to the project. The application should describe the management plan for the proposed center, and how it will support the goals proposed. It should describe the organization of the proposed center and its management structure, including integration of the separate components to form an efficient pipeline, key personnel, section leaders, and reporting relationships.. The applicant should discuss project management including how s/he would manage what are likely to be multiple ongoing collaborative relationships across many types of project. The plan should discuss how human subjects approvals associated with e.g., medical sequencing projects will be handled, in order to avoid this becoming a significant administrative bottleneck. The plan should describe how the various components of the proposed center will be integrated. The issue of how any other, ongoing large-scale sequencing projects would be integrated with the one to be funded under this FOA should be discussed.

Awardees must agree to the "Cooperative Agreement Terms and Conditions of Award" in Section VI "Award Administration Information".

Awardees and up to four additional key personnel from each center will be required to attend one research network meeting per year; applicants should request funds for this meeting.

II Large-Scale Sequencing Plan

This section (30 pages maximum) comprises the applicant's proposed plan for a large-scale genome sequencing center that will meet the objectives of this FOA. The organization suggested below for this section of the application is based on the NHGRI’s staff's current understanding of large-scale sequencing. The applicant is free to use an alternative presentation but, in so doing, must address all of the issues raised below.

II.1. Introduction including a one-page list of specific aims for the entire proposal, major scientific and technical directions and areas of emphasis for the center, a general justification for the importance of those areas, and why the current and near-future state-of-the-art in large-scale sequencing makes them appropriate opportunities.

II.2. Sequence production. The application should describe the sequence production component of the proposed center in the context of the overall sequencing objectives of the center and the NHGRI, the strategy or strategies the center will take to generate various sequencing products, the projected throughput, the expected or needed read characteristics and quality, and all other pertinent factors.

The applicant should present a clear plan, including concrete milestones, for meeting and exceeding the current state of the art in all areas of production sequencing discussed in this FOA, including whole genome sequencing, directed sequencing, de novo genome assembly, finishing/refinement, and others. All phases of the production process from sample acquisition through deposition of data--- must be addressed, as well as:

A. the overall projected cost and throughput of the proposed center, and how those will be attained for each type of production sequencing product. Costs, throughput, and quality must be discussed using the definitions given above in the description of the progress report for the Management Plan section. The most detail should be provided for the initial year of the award, including explicit cost and throughput projections for the final quarter of the first year (see suggested format at; applicants need not use this format, but all cost/throughput,/quality definitions should be used) but applicants should discuss overall plans and expectations, with justifications, for all years of the award. This discussion could also include, for example, expectations for changes in technology, and how anticipated new platforms will affect cost and quality of sequencing, and plans for adopting new platforms that are now available.

B. potential bottlenecks or other problems that can be anticipated, as well as proposed solutions;

C. timelines and quantitative milestones where appropriate, especially for throughput, cost, quality, and adoption of new technologies;

D. how the center will maintain the flexibility needed to produce the variety of sequencing products and to undertake the range of project types that have been discussed in this FOA.

II.3. Informatics and informatics development. Applicants should discuss the informatics that will be used to support sequence production, including routine IT/systems administration, LIMS, etc.

Applicants should discuss informatics pipelines that will be used in generating data for, and in aid of analysis for interpreting all different project types, for example for medical sequencing and related project types, the applicant should describe any informatics that would be used to interpret such data for example to identify reliable variants in heterozygotes. Applicants should discuss any proposed sequence assembly informatics that will be used in genome assembly.

Applicants may propose to develop new informatics for any of the areas above. In the application, a distinction should be made between routine or incremental improvements to existing software, and the development of entirely new capabilities (so-called radical informatics development). All development activities should be justified in terms of how they will improve sequencing throughput, efficiency, analysis and/or utility to the community. The costs of radical informatics development activities must be clearly described.

II.4. Analysis and Project Design. Because this FOA anticipates that centers will have analysis and project design capabilities, applicants should discuss how they will design projects, and should propose appropriate analysis methods and pipelines for the project types discussed above and any others proposed in the application. Note that while NHGRI expects centers to have analysis capabilities, we also expect that very extensive analyses may need to be done in collaboration with the wider community. Applicants should provide details in the about the extent of analysis to be done, justifying choices based on the utility of the data to the user community, and defining the point at which initial analysis (of medical sequencing projects, genome assemblies, finished genomes, etc.) will be considered to be complete enough for hand-off to the community.

II.5. Validation and Quality Assessment. Applicants should discuss their plans for validation and quality assessment for any major project types proposed.

II.6. Technology development. The Research Plan should include a separate section describing plans for technology development efforts to improve the efficiency of the production pipeline. Incremental and exploratory (or radical ) technology development should be discussed separately. Any issues involved in integrating new sequencing technology platforms into the production pipeline should be addressed. All technology development must be justified in terms of its utility for increasing efficiency of production or quality of the product, or for addressing new, compelling project types. Expected costs of technology development activities must be described.

II.7 Outreach and dissemination. The applicant should discuss how s/he would work with the various research communities that are consumers of sequence data, including a description of what the applicants believe is the best product for different research communities, the end-point for particular kinds of projects, and how s/he would propose to increase the ability of those communities to use the sequence data over the short- and long-term. The applicant is encouraged to demonstrate his/her ability to play this role by proposing collaborations, educational opportunities, and other means to develop a wider community of genomic sequence users. NHGRI has not set a limit on the portion of the budget that can be used for this activity, but the applicant must provide a clear description of plans for these activities and a well-justified budget request. The applicant should explicitly discuss the amount of funds proposed for these activities.

The applicant should also discuss how the center s activities will contribute to disseminating sequencing know how to the growing community of researchers with access to high-throughput sequencing capacity, including dissemination of important software tools, data formats, project designs, novel applications, etc.

II.7. Ongoing NHGRI projects. Applicants should discuss their commitment to, and plans for, participation in significant ongoing NHGRI projects, including TCGA, ongoing large medical sequencing projects, and the Genome Reference Consortium.

III Center Initiated Projects

A final research application section (no more than 12 pages) should propose center-initiated projects that will occupy approximately 50% of the initial 12-18 months of the applicant's sequencing capacity, with the understanding that existing and new NHGRI-selected projects may have priority. Center initiated projects (CIP s) may include ones that the center is already engaged in, but has not yet completed (if these are included they should be explicitly identified as such). Because there is not adequate space in the application to propose each project in detail, such project descriptions should be very brief (1-2 pages each). These projects should be justified in terms of their significance, how the sequence information will be used, and how they are appropriate for a large-scale center for example how they take best advantage of the current state-of-the- art in high-throughput sequencing; how they drive the development of important new project capabilities, how they are distinct from other projects going on at lower scale or by other means, etc. A brief sequencing plan, including a discussion of samples, costs, and duration should be included for each project. Ideally, the choice of ongoing and newly proposed CIP’s will illustrate of the overall scientific goals and priorities of the sequencing center, as described elsewhere in the application. The specific quality of individual center-initiated project plans (approach) will not be a significant component of the review. However, their overall combined level of significance, their appropriateness for taking best advantage of current high-throughput sequencing, and their potential contribution to defining or refining how similar projects could be done, will be considered in the review. See Section V. Applicant Review Information.

Other special guidance:

Diversity Action Plan Application. Applicants are required to submit a simultaneous, parallel application to the Initiative to Maximize Research Education in Genomics (R25) If your institution already has a Diversity Action Plan that is funded through NHGRI, contact program staff listed in this FOA.

Budget Request. The budget requested must be described clearly and be well justified. Applicants should submit the Detailed Budget for the Initial Budget Period (page 4 of PHS-398) and the Budget for Entire Proposed Period of Support (page 5 of PHS-398).

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 PHS398 Application Guide.


Do not use the appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS398 Application Guide,

Other information about application content and form

In addition to the instructions above regarding the three Research Plan sections, the application should include the following.

A resource sharing plan. NIH considers the sharing of unique research resources developed through NIH-sponsored research an important means to enhance the value of, and advance research. When resources have been developed with NIH funds and the associated research findings published or provided to NIH, it is important that they be made readily available for research purposes to qualified individuals within the scientific community. If the final data/resources are not amenable to sharing, this must be explained in Resource Sharing section of the application. See

Data sharing plan.

The application for a large-scale sequencing center is expected to include a plan for sharing research data. NHGRI strongly endorses rapid release of genomic data and materials. The specific NHGRI policy on release of sequence data is available at Because the purpose of this FOA is to fund large-scale sequencing centers, and the utility of such data is largely dependent on how quickly it can be deposited into public databases, NHGRI considers this FOA to be funding a community resource project as discussed in the report Sharing Data From Large-Scale Biological Research Projects - 2003: A System of Tripartite Responsibility available at The general NIH data sharing policy is available at All investigators responding to this funding opportunity should include a description of how research data will be shared.

Responses to this FOA should propose a plan for data release, as quality of the data release plan will be a criterion in the review of the application. Appropriate data release plans will be made a condition of the awards made as a result of this FOA. Each of the following items should be discussed separately:

Intellectual property management plan

A primary objective for the " Genome Sequencing and Analysis Centers is to maximize the public benefit of the data produced. Accordingly, awardees should manage intellectual property (IP) and data in a way that achieves this goal. In the case of the TCGA, as well as many of the medical sequencing projects, awardees are expected to generate a large collection of data that will serve as a foundation for the scientific community to develop future diagnostics, therapeutics and other medical applications. To achieve the objective of producing and broadly sharing the resources generated by both TCGA and the medical sequencing portion of the proposed sequencing capacity, applicants should develop a comprehensive IP and data management strategy that is consistent with the NIH Research Tools Policy ( and other NIH sharing policies ( Examples which applicants may wish to consider include the recommendations cited in NIH’s Best Practices for the Licensing of Genomic Inventions (

It is intended that the tools of scientific discovery necessary to rapidly and effectively develop new diagnostics, therapeutics and other medical applications be widely available for research use. Accordingly, awardees will be expected to manage IP in a way that is consistent with the goals of the initiative and in accordance with applicable NIH guidelines and best practices. Applicants should submit an IP Management Plan that assures that data is rapidly released according to approved criteria (see above), that licensing and sharing practices ensure the availability of data and research resources for future use by the scientific community, and that research collaboration or sponsorship agreements are consistent with meeting the goals and the requirements of the TCGA and the NHGRI medical sequencing program. IP Management Plans, once approved, will also become Terms and Conditions of award.

Restrictive licensing and sharing practices for TCGA and medical sequencing data could substantially diminish the value and public benefit provided by this community resource project. Management practices that would prevent or block access to, or use of TCGA or medical sequencing data and resources for research use will be considered to be hindering the goals of the NHGRI sequencing program. Applicants are encouraged to clearly demonstrate in their IP Management plan how their strategies will achieve the desired public benefit and programmatic goals through effective sharing of TCGA and medical sequencing data and tools.

Sharing Research Resources

NIH policy expects that grant awardee recipients make unique research resources readily available for research purposes to qualified individuals within the scientific community after publication (NIH Grants Policy Statement and Investigators responding to this funding opportunity should include a plan for sharing research resources especially significantly useful sequencing informatics tools-- addressing how unique research resources will be shared or explain why sharing is not possible.

The adequacy of the resources sharing plan and any related data sharing plans will be considered by Program staff of the funding organization when making recommendations about funding applications. The effectiveness of the resource sharing will be evaluated as part of the administrative review of each non-competing Grant Progress Report (PHS 2590, See Section VI.3. Reporting.

Applicants should discuss the following:

3. Submission Dates and Times

Part I. Overview Information contains information about Key Dates.

Information on the process of receipt and determining if your application is considered on-time is described in detail in the PHS398 Application Guide.

Applicants may track the status of the application in the eRA Commons, NIH s electronic system for grants administration.

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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.

Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, 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,

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.

Overall Impact

Reviewers will provide an overall impact/priority 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?

Is there a high likelihood that the proposed center can produce high-quality genomic sequence, based on the applicant’s past experience and the proposed future plans for generating high quality read data and other kinds of large-scale sequencing products as discussed in this solicitation? Is there a high likelihood that the applicants can accomplish this at and beyond current state-of-the-art levels of throughput, data quality, and cost?

Is there a high likelihood that the center will make significant contributions to the state-of-the-art in sequencing, including new applications and/or project designs for important types of project?

Are the questions being asked or approaches being developed by the applicant of high relevance for genomics in particular and biomedical science in general?

Considered as a collection, is the significance of proposed center-initiated projects high? Do they take good advantage of the current state-of-the-art in high throughput sequencing? Do they drive the state-of-the-art e.g. in adaptation of technology or project design? Do they have a high potential to make a significant contribution to defining or refining how similar projects could be done in the future by other groups with increasing access to significant sequencing capacity as costs decrease?

Is there a high likelihood that the center will provide significant leadership for sequence-based biology?


Are the PD/PIs, 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?

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?

Does the applicant have adequate plans for increasing throughput while lowering costs? Does the applicant have a successful record in this regard?

Has the applicant proposed creative applications that are likely to yield significant new knowledge in the field being studied?

Does the applicant have adequate plans for technology development related to large-sale sequencing, identifying and solving critical integration problems, and adopting new sequencing platforms to increase efficiency and lower costs? Does the applicant have a successful record in this regard?

Does the applicant have adequate plans for bioinformatics related to large-scale genomic sequencing, including infrastructure/laboratory information management, assembly, and primary annotation? Does the applicant have a successful record in this regard?

Is the proposed approach to sequencing adequate, especially as it may relate to the flexibility to address the variety of potential sequencing targets available? Does the applicant have a successful record in this regard?

Are the plans adequate for release of sequence data? Is there evidence that the systems are in place to support rapid data release? Are there adequate plans for release or distribution of other resources, software, or technologies developed under this award? Does the applicant have a successful record in this regard?

Is there an adequate management plan appropriate to the scope of the proposed work? Will the various components proposed be well-integrated?

If collaborations are proposed, for example with organism communities, investigators with human sample collections, or with other sequencing centers, are the plans adequate to ensure a productive collaboration? Does the applicant have a successful record of coordinating efforts with other large-scale sequencing centers in the U.S. and abroad? With disease and organism communities?

Does the applicant have adequate and forward-looking plans to disseminate information about genomes and to collaborate in effective ways with user communities? Does the applicant have a successful record in this regard?

For individual center initiated projects, the approach should not be incuded as a consideration.


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/priority score, but will not give separate scores for these items.

Special instructions for Section III of the Research Plan:

Section III of the Research Plan, "Center Initiated Projects" is intended to be reviewed as a collection with regard to their overall significance and/or novelty, rather than the specific approach for any single project. Per the instructions above, this section may include both ongoing center-initiated projects, or newly proposed ones, Criteria for evaluating the collection of Center Initiated Projects include:

Are they, as a collection, highly appropriate for pursuing at a large-scale sequencing center (of the scale sought by this FOA)?

Collectively, do they have high significance in terms of contribution to biological or biomedical science?

Do they advance the use of high-throughput sequencing for example in providing a motivation to modify technical approaches, requiring the development of new analytical methods, strategies, or project designs, particularly if these are likely to inform general approaches, or become early, good examples for similar project types undertaken by others in the field?

Do they generally highlight new opportunities or address gaps in the communities overall knowledge related to how to use large-scale sequencing to address important biological and biomedical questions?

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.


Not applicable


For Renewals, the committee will consider the progress made in the last funding period.


Not Applicable

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/priority score.

Applications from Foreign Organizations

Not applicable

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 National Human Genome Research Institute. (assignments will be shown in the eRA Commons), in accordance with NIH peer review policy and procedures, using the stated review criteria.

As part of the scientific peer review, all applications will:

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center and 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 on 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 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, CCR 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

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:

The P.I. of a genome sequencing production center will:

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

The Project Scientist will:

Areas of Joint Responsibility include:

The Steering Committee will:

Further terms and conditions relevant to The Cancer Genome Atlas program (TCGA)

In addition to the rights and responsibilities described above, the following rights and responsibilities will apply to the centers that participate in TCGA, a programmatic collaboration between NHGRI and the National Cancer Institute.

The P.I. of a Genome Sequencing Center that participates in TCGA will:

Project scientist responsibilities for TCGA:

Areas of joint responsibility for TCGA:

It is anticipated that decisions in all appropriate activities will be reached by consensus of the TCGA Research Network and that NHGRI and NCI staff will be given the opportunity to offer input to this process.

A Steering Committee will serve as the main governing board of the TCGA Research Network. The Steering Committee membership will include the NHGRI and NCI Project Scientist(s) and the P.I. of each of the awarded cooperative agreement for sequencing centers that engage in cancer genome sequencing and the P.I.s of each of the NCI-funded TCGA Characterization Centers. 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:

TCGA Panel of Scientific Consultants

The TCGA Panel of Scientific Consultants (PSC) will be responsible for reviewing and evaluating the progress of the members of the TCGA Research Network toward meeting their individual and collective goals. The PSC will be responsible for approving final plans for targeted sequencing undertaken by the centers. The ESC will provide recommendations to the Director, NHGRI and the Director, NCI about continued support of the components of the TCGA Research Network. The PSC is composed of senior scientists and clinicians with relevant expertise in genomics, cancer and ethics who are not P.I.s of a cooperative agreement involved in the TCGA Research Network. The membership of the PSC may be enlarged permanently, or on an ad hoc basis, as needed.

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

Reporting for TCGA

Awardees will be required to submit the PHS Non-Competing Grant Progress Report, Form 2590 annually ( and financial statements as required in the NIH Grants Policy Statement.

Awardees will also be required to submit periodic (quarterly) progress reports in a standard format, as agreed upon by the Steering Committee and the ESC.

Each awardee will be asked to define a set of yearly milestones for cancer genome sequencing at the time of the award and to update these milestones annually at the anniversary date. These will be made a condition of the award. In accord with the procedures described above, NHGRI may withhold or reduce funds for a project that substantially fails to meet its milestones or to maintain the state of the art. Sequencing

Human subjects. Many Medical Sequencing and Cancer sequencing projects entail sequencing of human samples. NHGRI has determined that applications in response to this FOA should indicate that they will use human subjects, even though most of the samples that will be sequenced will be anonymized and come from outside the center. Applicant institutions should ensure that adequate procedures are in place and that consideration will be given to potential human subjects issues associated with this award. Relevant policies for NHGRI are available at ( and for TCGA are available at

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.

3. Reporting

When multiple years are involved, awardees will be required to submit the Non-Competing Continuation Grant Progress Report (PHS 2590) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and Financial Status Report are required when an award is relinquished when a recipient changes institutions or when an award is terminated.

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

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Telephone 301-710-0267
TTY 301-451-5936

eRA Commons Help Desk(Questions regarding eRA Commons registration, tracking application status, post submission issues)
Phone: 301-402-7469 or 866-504-9552 (Toll Free)
TTY: 301-451-5939

Scientific/Research Contact(s)

Adam L. Felsenfeld Ph.D.
National Human Genome Research Institute ()
Telephone: 301-496-7531

Peer Review Contact(s)

Rudy Pozzatti, Ph.D.
Office of Scientific Review
National Human Genome Research Institute
5635 Fisher Lane
Suite 4076
Bethesda, MD 20892
Telephone: (301) 496-7531
FAX: (301) 435-1580

Financial/Grants Management Contact(s)

Cheryl Chick
Grants Management Branch()
Telephone: 301- 496-7531

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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