Notice Number: NOT-HG-19-007

Key Dates

Issued by
National Human Genome Research Institute (NHGRI)

Purpose

The National Human Genome Research Institute will issue multiple FOAs to fund a Human Genome Reference Program 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 (funding the Sanger Center and the European Bioinformatics Institute) and the National Center for Biotechnology Information.

The FOA is expected to be published in winter 2018 with an expected application due date in winter 2019.

This FOA will utilize the U41 activity code. Details of the planned FOA are provided below.

Research Initiative Details

This Notice of Intent covers one component of this overall activity, a Human Genome Reference Center (HGRC). The FOA will be released in conjunction with at least two other FOAs, one for High Quality Reference Genomes, and one for Research and Development for Genome Reference Representations. NHGRI intends to also fund related activities in Research and Development for Comprehensive Genome Sequencing, and Informatics Tools for the Pan-Genome. The awards under these FOA 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, there is need for improvement in several areas. First, the reference does not adequately represent human population genetic diversity. This will result 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, we need improved approaches for representing variation from multiple individual sequences, in order to fully capture human diversity in a pangenome , improve how that information is represented, and 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.

For this specific FOA, the HGRC will be the central group within the HGRP that will maintain and update the human reference. This group will also work with other HGRP members and the larger scientific community to prioritize sample choice and develop quality standards for new high-quality genome assemblies; implement state-of-the-art representations of alternate haplotypes (including those developed by other program components); identify and respond to diverse community needs (e.g., clinical and basic genomics), liaise with other resources that represent human genomic sequence and variation and/or that provide reference resources for human and other organisms. The HGRC is expected to integrate with the GRC and other international efforts that also have responsibility for providing genome references.

This program will not directly support genome reference work on data other than human.

The FOA will seek applications that address the following needs and activities:

1. Construct and release new human reference sequence versions (including patches and full updates); incorporating high quality human genome sequence data provided by another program component and from elsewhere if available; receive and resolve error reports.2.
2. Promote and adopt state-of-the-art reference representations that include alternative haplotypes. Provide basic tools for community use of the reference.
3. Provide community outreach and training for use of the reference; act as an aggregator of informatics tools created by the community for use of the reference.
4. Be the logistical and scientific coordinating center for the NHGRI HGRP, working to implement a framework for the human pangenome reference in a way that maximizes its value to the community.

Funding Information

Estimated Total FundingUp to $2,500,000 total costs.
Expected Number of Awards One
Estimated Award Ceiling Budgets must reflect the actual needs of the proposed project, but are not limited.
Primary CFDA Numbers 93.172

Anticipated Eligible Organizations

Inquiries

Please direct all inquiries to: