ABSTRACT
The AU of Us Research Program is building a national biomedical research resource from an
historically diverse population to empower and accelerate the understanding, diagnosis, and
treatment of human diseases in a representative and equitable way. The Broad Institute of MIT
& Harvard has a 35 year track record of delivering on transformative projects in the field of
genomics. Beginning with the Human Genome Project in the 1990s, our center has played a
leadership role in the design, data generation, and methods development in almost every major
genomic resource initiative that the NIH has launched. Over the last two decades, Broad has
sequenced the genomes of over 630,000 people, with >290,000 of those being for participants of
All of Us. Similarly, we have genotyped - 1.8 million samples with - 180,000 of those being AoU
participants. Color Health's clinical programming brings improved risk assessment,
identification, and disease management directly to large populations. Color's genetic services
laboratory (Color Dx) has sequenced and retumed clinical results to >200,000 individuals, with
as many as 10,000 results in a single month's time.
Together Broad and Color propose to continue to serve as a genome center and clinical
validation laboratory for the All of Us Program. Our group has a proven track record of high
quality data generation, collaboration across the AoU ecosystem, scaled capacity for retum of
results, and driving innovation through a suite of pilots, demo, and driver projects. We propose to
leverage our economies of scale to allow the program to meet all its commitments and maximize
value while also delivering new and powerful data types into the hands of the scientific
community. We propose an aggressive cost reduction and cost sharing plan to meet these goals.
We further offer a vision, for a future where additional funding is available, to accelerate
the adoption of the All of Us cohort data by providing a diverse set of pilot and demo project
proposals across the spectrum from innovative multiomic data generation, to longitudinal
studies, to elucidation of the interplay between exposures a participant may have had to markers
in their genetic, epigenetic, or proteomic profiles.
Our group brings together expertise in management of large scale genomics projects,
novel assay development, interpretation of human variation, clinical validation, regulations,
information security, and scientific vision. We also bring our network of scientific colleagues and
collaborators for the analysis of expression, long read, and proteomic data and for future studies
to further elucidate the mechanisms of complex traits and genes x environment interactions.
Specifically, for this award we propose to support the core genomic assays of whole
genome sequencing and genotyping at the desired scales, utilizing the same validated, secure,
and compliant workflows we have used over the last 5 years. We further propose to complete the
suite of innovative multiomic assays we have started on a core set of participants. We further
propose a variety of pilot, demo and driver projects that could be prioritized for future adoption
should additional funding be sourced.