Key Dates

Related Announcements

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-260 - PHS 2020 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)

PA-19-270 - PHS 2019-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)

RFA-HG-21-006 -Transformative Nucleic Acid Sequencing Technology Innovation and Early Development (R01 Clinical Trial not Allowed)

RFA-HG-21-007 -Transformative Nucleic Acid Sequencing Technology Innovation and Early Development (R21 Clinical Trial not Allowed)

Issued by

National Human Genome Research Institute (NHGRI)

Purpose

Purpose

The National Human Genome Research Institute (NHGRI) is issuing this Notice of Special Interest (NOSI) to encourage applications focused on developing novel laboratory-focused tools and technologies that enable new lines of scientific inquiry and clinical applications in human genomics.

Research Objectives

The field of genomics has repeatedly benefited from the development of new methodologies and substantial advances in genomic technologies. NHGRI seeks applications for genomic technology development research that would, if successful, have an impact in a three to seven-year time frame to move the field of genomics beyond the likely next steps in technological advances. It is expected that applicants will develop scientific and practical definitions of optimal cost, quality, bio-materials quantity, scale, time to result and other important features enabling the significant genomics technology development proposed. Ultimately these technologies should have the capability to be used in a high-throughput, production setting to generate high-quality data. Priority will be given to applications that propose improvements of at least an order of magnitude (based on state of the art at the time the application is submitted). Such improvements may be achieved by focusing on one critical factor or a combination of important ones.

Many proposals will benefit from computational elements planned as part of a well-integrated technology development effort. Co-development of methods for analysis of the new or improved data types generated can maximize usefulness and derive additional information content. However, work predominantly focused on computational approaches alone is beyond the focus of this notice for genomic technology development and may be more appropriate for other calls like Investigator Initiated Research in Computational Genomics and Data Science (R01 Clinical Trial Not Allowed along with the related R21 and R43/R44).

Some areas of NHGRI technology development interest, like research focused on Novel Synthetic Nucleic Acid Technology Development are covered by Requests for Applications (RFAs) (RFA-HG-20-014 , RFA-HG-20-015 and RFA-HG-20-016) and fall outside of the domain of this NOSI.

Background

The ability to assay a variety of genomic features extensively from a large and ever-growing knowledge base of genomic modifications and contextual information, coupled with the free dissemination of genomic data, have dramatically changed the nature of biological and biomedical research and have enabled advances in clinical applications of genetics and genomics.

Comprehensive genomic approaches have been made possible by the enormous reduction of costs, development of many informative assays, and the co-development or modification of companion bioinformatic tools. A broad swath of technology advances has enabled research projects that are producing stunning insights into genomics, genetics, biology and disease, as well as new clinical genomics applications. Extending beyond DNA sequencing, novel technologies have been developed for a range of genomic investigations, including those to determine contiguous chromosomal sequences, nucleotide modifications, somatic variation, gene regulation, chromatin state, nuclear organization, molecular phenotypic effects, and dynamics of those features. Nevertheless, the cost to perform a comprehensive evaluation of important features of genomes of single cells or mixed populations of cells remains high; some assays only indirectly measure the feature or function of interest; and many of the assays are complex to perform and implement, increasing the barriers to uptake. We remain far from consistently achieving direct measurements, precision, high quality, low costs, and rapid time to results needed to use comprehensive genomic information in many research applications and in individual health care.

Applicants are expected to work with the coordinating center NHGRI is establishing to accelerate technology development and progress in the field of genomics via RFA-HG-20-019). This includes attending and actively participating in a yearly grantee meeting to accelerate progress in the field. At that meeting, substantial information sharing will be expected as appropriate and consistent with achieving the goals of the Genome Technology Program (GTP). Intellectual property concerns will need to be managed appropriately in the context of these meetings and for other opportunities for information sharing. Grantees should also plan to work with the coordinating center as needed to assist in achieving the goals of this NOSI and the GTP, including collaborating to synthesize findings and disseminate advances, developing and promoting standards for genomic technologies, and facilitating technology transfer to research and clinical utilization, as appropriate

Research proposed in response to this NOSI should be generalizable, comprehensive, high-throughput and genome-scale. In some cases of very novel or new technologies, they may initially be developed at less than genome-scale as a proof of concept. In those circumstances, a justification should be given as to why the assay is an important area of interest at the pilot scale, along with a proposal for the potential to scale to genome-wide approaches.

Some examples of possible research topics are:

• Assays to quantify or map gene expression, chromatin accessibility, epigenomics, somatic variation, structural variation, epitranscriptomics, and nuclear architecture;
• Functional genomics technologies such as genome editing, base editing, epigenome editing, epitranscriptome editing or massively parallel reporter assays to comprehensively characterize regulatory elements, gene expression control or other aspects of genome function;
• Assays bringing spatial or temporal resolution to gene expression, chromatin accessibility, somatic variation, structural variation, epigenomics, epitranscriptomics or nuclear architecture;
• Methods measuring functional interactions between genetic variants and regulatory elements, in cis or trans;
• Methods that identify somatic variation in tissues, single cells or small sets of cells, and characterize related functional differences;
• Methods for epitranscriptome sequencing and detection of multiple specific modified bases;
• Methods to routinely sequence multi-megabase or larger regions of the genome in a phased manner including difficult to resolve regions;
• Methods for native, full length and comprehensive direct RNA sequencing;
• Molecular phenotyping methods to assay the effects of genetic variation on any of the functional data types above;
• Multiple informative assays on the same sample;
• Methods for single-cell or sub-cellular resolution for the kinds of assay examples above;
• Genomic recorders that track the activity of genes, regulatory elements, cell lineage or cell fate;
• Methods for sample and library preparation along with direct native nucleic acid sequencing that ideally includes modified base determinations; and
• Improvements of accuracy, throughput, and parallelization of nucleic acid sequencing.

Application and Submission Information

This notice applies to due dates on or after February 5, 2021 and subsequent receipt dates of current and reissued FOAs through January 10, 2024.

Applications for this initiative must be submitted using any of the following funding opportunity announcements (FOA) or any reissues of these announcements through the expiration date of this notice:

PA-20-185 - NIH Research Project Grant (Parent R01 Clinical Trial Not Allowed)

PA-20-195 - NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

PA-20-260 - PHS 2020 Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications (Parent SBIR [R43/R44] Clinical Trial Not Allowed)

PA-19-270 - PHS 2019-02 Omnibus Solicitation of the NIH for Small Business Technology Transfer Grant Applications (Parent STTR [R41/R42] Clinical Trial Not Allowed)

Applicants are encouraged to contact NHGRI staff early in the application process, and also to review the NHGRI guidance to potential applicants for NHGRI support: https://www.genome.gov/research-funding/Funding-Opportunities/guidance.

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

• For funding consideration, applicants must include NOT-HG-21-018 (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.

Inquiries

Scientific/Research Contact(s)

Stephanie A. Morris, Ph.D.

National Human Genome Research Institute (NHGRI)

Telephone: 301-435-5738

Email: [email protected]

Peer Review Contact(s)

Examine your eRA Commons account for review assignment and contact information (information appears two weeks after the submission due date).

Financial/Grants Management Contact(s)

Monika Christman

National Human Genome Research Institute (NHGRI)

Telephone: 301-435-7860

Email: [email protected]