UG3HG014376

PATIENT CENTERED PREDICTION OF CLINICALLY IMPORTANT OUTCOMES ARISING FROM PATHOGENIC VARIANTS - PROJECT SUMMARY / ABSTRACT AS GENETIC TESTING BECOMES MORE COMMON IN MEDICAL CARE, AN INCREASING NUMBER OF INDIVIDUALS WILL DISCOVER THAT THEY CARRY A PATHOGENIC VARIANT. FOR SOME, THIS RESULT WILL EXPLAIN CURRENT SYMPTOMS AND AID IN DIAGNOSIS. FOR OTHERS, THE FUTURE HEALTH IMPACTS OF A PATHOGENIC VARIANT MAY BE LESS CLEAR, CAUSING UNCERTAINTY BUT ALSO PRESENTING AN OPPORTUNITY TO PREVENT OR MITIGATE SERIOUS HEALTH OUTCOMES IN THE FUTURE. THIS UNCERTAINTY ARISES FROM INCOMPLETE PENETRANCE AND VARIABLE EXPRESSIVITY. WHETHER A SYMPTOM MANIFESTS IN A CARRIER DEPENDS ON NUMEROUS INDIVIDUAL FACTORS (ONLY SOME OF WHICH ARE KNOWN), CREATING A DILEMMA FOR PRACTITIONERS REGARDING WHETHER AND HOW TO INTERVENE. USING WHAT WE CAN LEARN FROM PAST CLINICAL EXPERIENCE IN VARIANT CARRYING INDIVIDUALS CAPTURED IN A GROWING NUMBER OF RESOURCES LIKE BIOBANKS, WE CAN ADDRESS THIS CLINICAL DILEMMA BY CREATING A MACHINE LEARNING / ARTIFICIAL INTELLIGENCE (ML/AI) TOOL THAT PREDICTS THE LIKELIHOOD A PATHOGENIC VARIANT CARRIER WILL DEVELOP DISEASE. BUILDING ON OUR EXTENSIVE EXPERIENCE IN CREATING COMPUTABLE AND PORTABLE PHENOTYPES FROM DATA IN THE ELECTRONIC HEALTH RECORD (EHR) THAT ACCURATELY REPRESENT CLINICAL TRAJECTORIES IN PATHOGENIC VARIANT CARRIERS, WE PROPOSE TO REFINE OUR UNDERSTANDING OF DISEASE PREDICTION BY MODELING FACTORS AFFECTING VARIANT EXPRESSIVITY AND USING LONGITUDINAL PATIENT TRAJECTORIES TO IDENTIFY EARLY, OFTEN SUBTLE, PHENOTYPIC INDICATORS OF DISEASE PROGRESSION. FINALLY, WE WILL USE A BAYESIAN TRANSFER LEARNING APPROACH TO SYNTHESIZE MULTIMODAL DATA FOR GENERATING INDIVIDUALIZED PREDICTIONS OF RISK OF KEY CLINICAL OUTCOMES IN THE CONTEXT OF A GIVEN PATHOGENIC VARIANT. TO DEVELOP A VIABLE MODEL FOR CLINICAL TRANSLATION THAT ADDRESSES THE SIGNIFICANT RISKS AND CHALLENGES ASSOCIATED WITH DEVELOPING ML/AI TOOLS, WE WILL EMPLOY A KNOWLEDGE-GUIDED FRAMEWORK THAT INCORPORATES INPUT FROM ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) EXPERTS, CLINICIANS, STATISTICIANS, GENETICISTS, AND INFORMATICIANS AT EVERY STAGE OF THE DESIGN PROCESS, FROM DEFINING KEY CLINICAL OUTCOMES, SELECTING AND ENGINEERING MODEL INPUTS, AND DEVELOPING APPROACHES TO COMMUNICATE PREDICTIONS TO PATIENTS AND PROVIDERS. OUR FRAMEWORK WILL ALLOW US TO SYNTHESIZE CURRENT KNOWLEDGE OF PATHOGENIC VARIANTS WITH THE PATTERNS MINED FROM REAL-WORLD DATA WHILE ADDRESSING THE SIGNIFICANT ELSI CONCERNS INHERENT IN ML/AI TOOL DEVELOPMENT. OUR PROPOSAL BRINGS TOGETHER A TRANSDISCIPLINARY TEAM OF EXPERTS IN INFORMATICS, ETHICS, MACHINE LEARNING, CLOUD COMPUTING, GENOMICS, AND CLINICAL MEDICINE, AND LEVERAGES EXCEPTIONAL LOCAL DATA RESOURCES TO BRING THE POTENTIAL OF ML/AI GENOMIC MEDICINE. WITH THIS INNOVATIVE PROPOSAL, WE AIM TO CREATE RESOURCES THAT WILL ENABLE THE DEVELOPMENT AND VALIDATION OF VALUABLE GENOMIC MEDICINE TOOLS FOR THE FUTURE.

Vanderbilt University Medical Center

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]

Nashville, Tennessee 37203 United States

Single Zip Code

ML/AI Tools to Advance Genomic Translational Research (MAGen) - Development Sites (UG3/UH3 Clinical Trials Not Allowed) (RFA-HG-24-004)

Amendment Since initial award the total obligations have increased 3% from $3,073,346 to $3,173,346.