U24HG011453

The Association to Function Knowledge Portal: A Genomic Data Resource for Translating GWAS Associations to Biological Effects - Abstract

Genome-wide association studies (GWAS) have produced associations between many thousands of genetic variants and many hundreds of traits. The "functional effects" of most associations, however, have not yet been elucidated – that is, the causal variants and effector genes responsible for them, and the tissues and pathways through which they act, remain largely unknown.

Over the past few years, three classes of genomic data have arisen for inferring the functional effects of GWAS associations: summary association statistics (effect sizes and p-values for associations between SNPs and traits), genomic annotations (assays of regulatory activity and genomic functional elements), and bioinformatic methods (computationally predicted functional effects).

We argue that two gaps exist in the current resources that aggregate these data: first, no current resource aims to comprehensively curate and catalog all that is known, and all data or methods that could help predict, the functional effects of GWAS associations; second, existing resources are developed with (at best) limited involvement from experts who either originally generated the genomic data and/or understand how to best use them.

We propose to address these gaps by building a new genomic community resource – the Association to Function Knowledge Portal (A2FKP) – using a general software platform we initially developed for type 2 diabetes. Our approach makes use of a key innovation to build a resource that is both high quality and comprehensive: we collaborate with disease expert communities to build dedicated knowledge portals for them, motivating them to contribute their data and expertise, and we then integrate these data alongside those of other communities, providing users with access to a comprehensive resource.

Specific Aim 1 addresses gaps in the comprehensiveness and quality of the data aggregated by current resources regarding the functional effects of GWAS associations. It will establish and manage collaborations with a wide range of disease, data, and method experts, and then work with these communities to identify, aggregate, and curate data for 11 classes of disease.

Specific Aim 2 addresses gaps in current schemas and software platforms for the myriad types of data used for predicting the functional effects of GWAS associations. It will build pipelines for processing genetic and genomic datasets through bioinformatic methods for predicting the functional effects of GWAS associations, apply these pipelines to data aggregated in Aim 1, and transform their outputs to relationships among entities in a knowledge graph.

The goal of Specific Aim 3 is to provide users with direct and visual access to the resources aggregated or computed in Aims 1 and 2. It will develop REST APIs and web portals for querying and visualizing data within the A2FKP.

Significance: The project would produce a high-quality and comprehensive genomic resource of data and methods for predicting the functional effects of GWAS associations. Easy access to such a resource will accelerate the pace by which GWAS associations can be translated into insights into complex disease.

The Broad Institute

NHGRI SUPPORTS THE DEVELOPMENT OF RESOURCES AND TECHNOLOGIES THAT WILL ACCELERATE GENOME RESEARCH AND ITS APPLICATION TO HUMAN HEALTH AND GENOMIC MEDICINE. A CRITICAL PART OF THE NHGRI MISSION CONTINUES TO BE THE STUDY OF THE ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) OF GENOME RESEARCH. NHGRI ALSO SUPPORTS THE TRAINING AND CAREER DEVELOPMENT OF INVESTIGATORS AND THE DISSEMINATION OF GENOME INFORMATION TO THE PUBLIC AND TO HEALTH PROFESSIONALS. THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM IS USED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM IS USED TO FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.

93.172 - Human Genome Research

National Human Genome Research Institute (NHGRI) [HHS - NIH]

Cambridge, Massachusetts 021421027 United States

Single Zip Code

Genomic Community Resources (U24) (PAR-17-273)

Amendment Since initial award the total obligations have increased 382% from $710,735 to $3,423,032.