Trialect

Active

Notice of Special Interest (NOSI): Methods Development for Genomic Studies of Genetic Variation, Function, and Disease

National Institutes of Health

The National Human Genome Research Institute (NHGRI) is issuing this Notice of Special Interest (NOSI) to encourage applications that develop novel computational or experimental approaches for genomic studies of how genetic variants relate to genomic function, phenotype, and disease.

The Human Genome Project produced the reference human genome, and then projects such ENCODE characterized many functional elements in the genome. Projects such as the International HapMap Project, the 1000 Genomes Project, and many disease sequencing studies found over 900 million variant sites in the genome. Many genome-wide association (GWAS) studies discovered statistical associations among these variants and numerous diseases and traits. The Impact of Genomic Variation on Function (IGVF) Consortium is an NHGRI project to develop a framework for systematically understanding the effects of genomic variation on genome function and how these effects shape phenotypes.

Relating variants to function and disease risk is a large scientific area. The key open question is: How do variants in genomic elements result in differences in how those genomic elements function, resulting in differences in regulation and molecular phenotypes that lead to differences in disease risk or traits? An understanding of these risk variants can contribute to personalized risk prediction and the development of therapies focused on risk variants.

Even with the efforts mentioned above, new methods are still needed; many new ideas in this field will be best developed through investigator-initiated work such as called for in this NOSI.

NHGRI seeks applications that will develop methods to provide a better understanding of how genetic variation relates to function, phenotype, and disease risk or traits. For this NOSI, the term “disease risk or traits” is used broadly, to encompass diseases, risk of diseases, protective effects against diseases, molecular phenotypes, organismal phenotypes, clinical phenotypes or outcomes, traits, responses to therapeutic drugs or vaccines, and other outcomes relevant to human health and disease.

The focus should be on developing approaches that can be applied generally to many or all genes, variants, diseases, or phenotypes. Approaches may be developed and tested using specific genomic elements, variants, cell types, diseases, traits, regulatory interactions, or networks; however, the generalizability of the approach must be explained well. Approaches that are comprehensive across the genome and assay many or all variants at once are encouraged. This NOSI is not intended for approaches that are only applicable to or focus on specific diseases, genes, or variants. This NOSI aims to support the development of novel approaches, so applications whose major aim is the production of data sets using existing approaches are also not appropriate for this NOSI.

This notice applies to receipt dates on February 5, 2022, and subsequent ones through October 5, 2024, for new applications, and November 5, 2024, for renewal and resubmission applications.

NOT-HG-22-007