Featured Speakers and Presentation Content
Joshua C. Denny, M.D., M.S.
ABSTRACT: We will introduce the session by briefly presenting an overview of the All of Us Research Program and progress to date in the program’s efforts to drive participant engagement, build a data-driven enterprise supporting research, and develop more effective ways to improve health outcomes. All of Us is building a national research cohort of one million or more participants with rich diversity, particularly including those underrepresented in biomedical research, and is currently enrolling adults age 18 and older in the United States. Participants are recruited through more than 350 enrollment clinics across the United States through both health care provider organizations and direct volunteer sites. The longitudinal data collections include health surveys, electronic health records, physical measurements, biospecimens, and digital health data. To date, more than 350,000 participants have signed consents to share data, and more than 270,000 participants have completed all core aspects of the program. More than 80% of the core participants represent populations historically underrepresented in biomedical research.
Engaging Underrepresented Research Participant Communities in Genomic Research
Consuelo H. Wilkins, M.D., M.S.C.I.
ABSTRACT: It is increasingly apparent that to be relevant and impactful, research must engage individuals outside the research communities, such as patients, participants, and community representatives. Yet this type of engagement typically occurs in community-based participatory and patient-centered outcomes research, not large-scale genomics or precision medicine research. The All of Us Research Program, which will enroll at least one million participants from diverse backgrounds, has committed to actively engaging participants as partners in all aspects of the program—from research design through governance. With guiding principles on privacy and trust and a mission to empower participants, All of Us intends to promote transparency, reciprocity, and involvement of participant communities in the governance, oversight, design, implementation, and evaluation of the program. This engaged and participant-centric approach represents a substantial shift in large biomedical research initiatives, which until recently had little, if any, public involvement. This presentation will discuss lessons learned by the All of Us Engagement Core in developing the infrastructure, tools, and resources to meaningfully engage participants as partners. Key areas of emphasis will include identifying and selecting a diverse group of participants to engage at multiple levels in the program; effectively engaging participants as members of the executive committee, steering committee, and other governance bodies; eliciting input from participants in the design, conduct, and return of value; assessing the impact of participant engagement on the research; and preparing researchers, including those with limited experience in engagement, to work with participants from diverse backgrounds in these roles.
Innovative Sequencing and Array Technologies at All of Us
Richard A. Gibbs, AC, Ph.D.
ABSTRACT: A foundational activity within the All of Us Research Program is the generation of genomic data from participants, with the eventual goal to have completed whole genome sequences (WGS) for all, with exhaustive and complete interpretation of all possible genetic factors. Genome sequencing is, however, a demanding and evolving technology. To maintain the most valuable ongoing data generation and analysis of participants’ samples while both adopting and exploring innovations in genome methods, All of Us is utilizing a staged data generation and interpretation approach. First, a state-of-the-art Illumina technology–based array genotyping has been established. A custom DNA chip has been produced with more representation of DNA variation from diverse populations than ever before. This DNA chip contains approximately 1.9 million sites and will inform ancestry, some recreational genetic traits, many pharmacogenetic markers, and known disease alleles. As the program moved toward genome data production, a refined version of the chip was produced to optimize these capabilities. Meanwhile, the default WGS pipeline was established using the latest Illumina DNA sequencing chemistry. The three participating All of Us Genome Centers established optimal parameters for sample management and processing and agreed on stringent quality control standards. A harmonized and unified analysis pipeline was also crafted, resulting in equivalent WGS products being produced at each site. These methods can produce the best available genome data at this time. As an ongoing exercise, alternate technologies are being evaluated and tested, including the generation of “long DNA reads” using the Pacific Biosciences and Oxford Nanopore Technologies platforms. If advantageous and cost-effective, these new data types may be incorporated for genome sequence analyses from All of Us Research Program participants. All data are also subject to potential reanalysis to take advantage of any developments in analytical software that may, for example, improve the accuracy of calling specific classes of genetic variation, such as DNA repeats. In aggregate, the All of Us Research Program is ideally situated to both provide the best possible current genomic data and quickly take advantage of any technical developments for further improvements.
Returning Genetic Results at the Population Scale
Alicia Zhou, Ph.D.
ABSTRACT: The All of Us Research Program has already recruited more than 350,000 participants who offer their health and genomic information for the purposes of scientific research. A key aspect of the partnership with participants is the return of genomic results, which involves many challenges and considerations, especially considering the broad diversity of the participants. We will describe the All of Us approach to responsible return of health-related results at scale to participants, with a focus on delivering genetic findings tied to 59 genes associated with risk of specific hereditary disease conditions. Over the course of the program, we expect that 2% to 3% of participants will have a positive result, such as a pathogenic variant in the BRCA1 gene, that may be important for treatment or screening. Therefore, we will also highlight the support framework that exists to educate participants about their results and to provide genetic counseling, a hand-off to medical care, and advice for cascade testing. Finally, we will discuss the return of recreational genetics, such as non–health-related traits and genetic ancestry, that have been among the top requests from All of Us participants. These insights will be delivered to participants through a user-friendly, web-based platform. In the first year, we expect to return results to more than 10,000 participants, including 200 to 300 positive results. We will assess the consequential operational metrics, including technical, engagement, satisfaction, and population characteristics.
Pharmacogenomic (PGx) Framework and Approach for PGx Return of Results
Philip Empey, Pharm.D., Ph.D.
ABSTRACT: PGx data are increasingly valued by health care providers and patients as a wealth of information associating genetic variation with differences in drug pharmacokinetics and response. The All of Us Research Program is committed to returning PGx results as well as other medically actionable information, such as hereditary diseases risk reports, to diverse groups of participants. Returning PGx results and delivering maximum value while mitigating potential risks is challenging and has additional complexity because of the diverse genetic backgrounds of the participants. Whole genome sequencing will be conducted in the All of Us Genome Centers, and participants will obtain their PGx reports from the All of Us Data and Research Center through engaging and participant-centric processes. The program has been working closely with the Food and Drug Administration (FDA) to return these research results with drug information that is supported by the highest level of evidence. This presentation will discuss the program’s highly collaborative efforts to achieve program goals through a robust PGx testing framework and return-of-results strategy. We will also discuss the approaches to consideration of rare alleles that are specific to ethnic groups. Our guiding principles for gene/allele selection and the reporting of actionable findings will be discussed with a particular focus on evidence review. Finally, the design of the report to achieve high user comprehension and sharing of results with health care professionals will be discussed.
Researcher Workbench Demonstration and Developing Tools for Genomic Analyses
Andrea Ramirez, M.D., M.S.
ABSTRACT: The All of Us Research Program is committed to the ambitious mission of collecting health data from one million or more participants to accelerate scientific discoveries in precision medicine. Delivering on this mission will result in the largest biomedical research dataset ever assembled. At this scale, downloading a dataset and storing it locally is expensive and impractical. Moreover, few researchers will have the necessary computational or security infrastructure to perform local analyses on such a large dataset. To address challenges in cost, accessibility, and security, the All of Us Data and Research Center brings researchers to the data in a cloud-based analytical platform, known as the All of Us Research Hub, that meets robust security and regulatory requirements. Contained in the Research Hub is the Researcher Workbench, which includes user-friendly tools for study cohort identification and characterization for feasibility testing, data exploration, covariate selection, and analysis. This presentation will show the expansion of the Workbench tools to accommodate genomic data and early looks at scalability and performance and to delve into Consortium efforts to demonstrate the quality, utility, and diversity of genomic data generated for general research use.
Learn more about joining the All of Us Research Program.