Notice Number: NOT-HG-19-009
Key DatesRelease Date: October 25, 2018
National Human Genome Research Institute (NHGRI)
The National Human Genome Research Institute will issue multiple FOAs to fund a Human Genome Reference Program (HGRP) that is intended to replace and update its current commitment to activities now undertaken by the Genome Reference Consortium (GRC). The GRC provides a resource used by essentially all researchers who need to align and read-map experimental or patient genome sequence data. It also serves as a consensus coordinate system for reporting results. The GRC improves the reference, curates and releases updates and new reference builds, develops representations and alignment tools so that the community can use the reference and alternative haplotype information within it, resolves error reports from the community, and performs outreach. The GRC operates as an international consortium, with support provided by NHGRI, as well as the Wellcome Trust and the National Center for Biotechnology Information.
This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.
The FOA is expected to be published in the winter of 2018 with an expected application due date in the winter of 2019.
This FOA will utilize the U01 activity code. Details of the planned FOA are provided below.
Research Initiative Details
This Notice of Intent covers one component of this overall activity, Research and Development for Genome Reference Representations (GRR). The FOA will be released in conjunction with at least two other FOAs, one for a Human Genome Reference Center (HGRC), and one for production of High Quality Human Reference Genomes (HQRG). NHGRI intends to also fund two related activities in Research and Development for Comprehensive Genome Sequencing and Informatics Tools for the Pangenome. The awards under these FOA will constitute the NHGRI Human Genome Reference Program (HGRP). Successful applicants for this and related FOA are expected to collaborate with each other, and with other international resources and efforts related to genomic references. NHGRI will seek competitive applications from all eligible institutions, whether currently supported for human genome reference activities or not.
As an outgrowth of the International Human Genome Project, the current human genome reference has sustained and supported genomic research for more than the last decade. However, the opportunity for improvement has developed in several areas. First, the reference does not adequately represent human population genetic diversity. This results in suboptimal ability to map short-read genome sequencing data to the reference, in a way that is biased to favor the populations already represented in the reference. Second, it is clear that additions of multiple new individual sequences to the reference will require development of improvements to the ways that the information is represented, in order to ease computation and downstream use. Third, the community of users of the reference continues to expand and diversify, meaning that new informatics tools will need to be developed to make the reference easily usable for multiple communities.
A key goal of the new HGRP is the development of a human reference that faithfully and usefully represent sequences from diverse haplotypes and populations. Currently the linear genome reference has been extended to include alternative pathways (“alt paths”) that are added on top of standard reference sequence to show some population-based variation. However, there is a recognized need for more advanced representations, such as graph representations. A full graph representation is expected to provide better ways to understand haplotype diversity and complex variation such as structural variation, copy number variation, and repetitive sequences. Graph methods may also support efficient genome data management by compressing out redundancy in population-based sequences and enable use of network algorithms developed in other domains.
The specific purpose of this FOA will be to develop improved representations of the information in the increasing numbers of diverse genome assemblies that will make up the human reference sequence. While the concept of the graph representation of the pangenome is well-established, further research and development is needed to refine and implement it to be usable as a practical human genome reference. Work is needed to demonstrate efficiency, scalability, computational speed, ease of use, adoption, and ability to foster analysis tool development for a wide range of purposes. In addition, next-generation representations other than graph representations may emerge. An FOA would fund multiple projects that will together help set benchmarks and standards in this domain for a pangenome representation. A primary requirement is to adhere a high level of open science including open-source tools, standards, and specifications to enable this core resource to be integrated in the larger community and support outside contributions.
Representations developed by this effort will be candidates for adoption within the HGRC. However, successful efforts should also be independent and based on common standards. This would allow for the field to evolve to allow for broader efforts, such as the development of community specific references.
Applicants should anticipate that they will be working collaboratively with the NHGRI HGRP as a whole, especially for the purposes of implementing representations as part of the human genome reference through the HGRC, interacting with downstream user tool development, and helping to assess the overall quality of the reference resource.
In general, this program will not directly support genome reference work on other than human, we expect that methods and tools developed under this FOA will be applicable broadly.
NHGRI anticipates accepting applications in this area both under this specific FOA, and also under its regular programs.
Estimated Total Funding Up to $1,500,000 total costs per year.
Expected Number of Awards four
Estimated Award Ceiling Application budgets must reflect the actual needs of the proposed project, but are not limited to the total cost limit.
Primary CFDA Numbers 93.172
Anticipated Eligible Organizations
Public/State Controlled Institution of Higher Education
Private Institution of Higher Education
Nonprofit with 501(c)(3) IRS Status (Other than Institution of Higher Education)
Nonprofit without 501(c)(3) IRS Status (Other than Institution of Higher Education)
For-Profit Organization (Other than Small Business)
Indian/Native American Tribal Government (Federally Recognized)
Indian/Native American Tribally Designated Organization (Native American tribal organizations (other than Federally recognized tribal governments)
U.S. Territory or Possession
Indian/Native American Tribal Government (Other than Federally Recognized)
Please direct all inquiries to:
Rudy O. Pozzatti, Ph.D.
National Human Genome Research Institute
For Fiscal Information
Ms. Deanna Ingersoll
National Human Genome Institute