U01HG012069

Predicting Context-Specific Molecular and Phenotypic Effects of Genetic Variation through the Lens of the Cis-Regulatory Code - Abstract

A central challenge in human genomics is to interpret the regulatory functions of the noncoding genome and to identify and interpret variants with regulatory functions. In this project, we plan to leverage recent advances in experimental functional genomics, including single-cell methods and high-throughput perturbation methods, alongside recent progress in deep learning models of gene regulation, to make fundamental progress on these problems.

We have assembled a team of investigators with diverse and complementary expertise in deep learning, single-cell genomics, cellular QTLs and GWAS, and high-throughput validations. Our goal is to build, test, and implement predictive models for interpreting disease associations. Specifically, we aim to:

(1) Develop interpretable base-resolution deep-learning models for regulatory sequences.

(2) Predict and validate cell type-specific effects of regulatory variants on molecular phenotypes and disease.

(3) Collaborate with the IGVF Consortium to build nucleotide-level regulatory maps.

Our ultimate goal in this project will be to create a nucleotide-resolution cis-regulatory map of the human genome to connect disease variants to functions and phenotypes in diverse cell types, states, and spatial contexts.

The Leland Stanford Junior University

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]

Palo Alto, California 943041049 United States

Single Zip Code

Developing Predictive Models of the Impact of Genomic Variation on Function (U01 Clinical Trial Not Allowed) (RFA-HG-20-047)

Amendment Since initial award the total obligations have increased 818% from $352,213 to $3,232,570.