Leveraging All of Us Biospecimens to Advance Precision Medicine Research

The All of Us Research Program is interested in partnering with NIH ICOs to fund investigator-initiated applications that leverage already-collected All of Us biospecimens to learn more about how differences in lifestyle, environment, and biology influence health and disease. 

Areas of interest include: 

• Large-scale projects that make optimal use of participant-donated biospecimens
• Generation of data on the entire population or large subsets of participants 
• Broadly applicable assays with the potential to provide insights into biological pathways that underlie common, chronic, or pressing health conditions
• Assays that generate data that are applicable to a broad range of future scientific questions from registered researchers on the All of Us Researcher Workbench 

The National Center for Complementary and Integrative Health (NCCIH) is interested in studies using genomics, epigenomics, proteomics, metabolomics, immune profiling, and other multi-omic approaches to elucidate the biological, behavioral, social, and environmental factors that promote health, resilience, and whole person health outcomes are encouraged. NCCIH also supports research on interactions among physiological systems; biomarkers of pain, recovery, and treatment response; and mechanisms underlying the transition from acute to chronic pain and its resolution. Applications that create broadly useful datasets, promote data sharing, reuse and integrate new data into the All of Us Researcher Workbench (e.g., the Whole Person Health Index) are strongly encouraged.

NCI is interested in investigator-initiated applications utilizing All of Us biospecimens to generate data to address questions relevant to NCI's mission of supporting innovative cancer research aimed at improving cancer prevention, detection, diagnosis, treatment, and survivorship.

 Areas of Interest (Examples):

• Studies using All of Us biospecimens to generate multiomic data to elucidate cancer susceptibility, cancer biology, the exposome, and modifiable risk factors and their contributions to cancer risk and outcomes (e.g., survival, treatment response, quality of life) 
• Molecular epidemiology studies using biospecimen-based approaches to investigate familial cancer, exposures, and U.S. regional variation in cancer risk and outcomes
• Studies using biospecimens to support the discovery, development, or validation of novel cancer diagnostic, predictive, or prognostic biomarkers, including those to improve cancer screening, early detection, and treatment-related adverse effects

NEI is interested in investigator-initiated applications using All of Us biospecimens with available eye imaging, genomic, clinical, survey, and participant data to address questions relevant to NEI’s mission to prevent and treat eye disease and vision loss. NEI encourages studies that use these resources to define molecular, genetic, and systemic features of ocular health and disease. 

Areas of interest include:

• Generating and integrating multi-omic data with All of Us genomic, clinical, phenotypic, and retinal or other ophthalmic imaging data.
• Linking biospecimen-derived data with imaging-derived ocular phenotypes to identify biomarkers, pathways, and predictors of disease risk or progression.
• Developing computational or AI/ML approaches combining molecular, imaging, electronic health records (EHR), and participant-reported data.
• Examining drivers of eye health and vision disparities.
• Generating multimodal datasets, tools, or resources for vision research.

NHGRI is interested in investigator-initiated applications using existing All of Us biospecimens to address questions relevant to NHGRI's mission.

NHGRI is particularly interested in large-scale genomic and multiomic analyses that complement the cohort's existing short-read whole genome sequence data. Of specific interest are applications that:

• Generate long-read sequencing data to capture genomic variation missed by short-read approaches, including structural variants, repeat expansions, and complex regions.
• Integrate new multiomic data layers (epigenomic, transcriptomic, proteomic, metabolomic) with All of Us genomic and phenotypic data to advance understanding of gene function, regulation, and genotype-phenotype relationships.
• Develop new methods to examine the genomic and molecular basis of diseases or traits, leveraging the cohort's large, ancestrally diverse population.
• Produce broadly accessible, population-scale multiomic reference datasets for the genomics community.

NIAAA encourages applications leveraging All of Us biospecimens and linked clinical data to characterize biological states associated with alcohol exposure, alcohol-associated disease, treatment response, recovery, and prevention. Although biospecimens were collected cross-sectionally, they capture molecular states representing a snapshot of individual biology at sampling that can be linked to subsequent clinical outcomes.

Areas of interest include:

• Generation and integration of multiomic data to define biological states.
• Identification of molecular endotypes of AUD and alcohol-associated organ injury not captured by conventional diagnoses.
• Integration and harmonization of multiomic, clinical, environmental, and complementary external datasets for discovery and cross-study replication/validation.
• Development of scalable multiomic pipelines and reference resources.
• Studies that leverage biological states to inform individualized prevention and treatment.

NIAMS is interested in applications that use All of Us biospecimens for multi-modal data analyses to advance understanding of biological mechanisms underlying arthritis, musculoskeletal, and skin diseases.

Applications of interest using All of Us biospecimens include, but are not limited to:

• Generate multi modal data (e.g., epigenomic, transcriptomic, proteomic, metabolomic) from All of Us biospecimens to elucidate biological mechanisms underlying NIAMS conditions. 
• Integrate newly generated multi omic data with existing All of Us resources (e.g., genomics, environmental, electronic health records, and surveys) to enhance diagnosis, phenotyping, and biomarker discovery; improve assessment of disease risk and progression, treatment response, and health outcomes; and advance precision medicine approaches for the diverse populations. 
• Leverage biospecimens to define cellular and molecular causal mechanisms, and tissue level signatures that inform therapeutic target identification. 

NICHD is interested in applications that leverage All of Us Research Program biospecimens to advance health and functioning across the lifespan. Interests include but are not limited to: 

• Biomarker, multiomic, and other biospecimen-derived approaches to investigate biological, environmental, behavioral, and social factors that influence health relevant to priority populations outlined in the NICHD strategic plan. 
• Development of datasets that accelerate discoveries to improve health across and within populations 

Applicants are strongly encouraged to contact a NICHD program official prior to submission.

NIDA is interested in discovering biomarkers to diagnose, predict trajectories, and treatment outcomes for substance use disorders. The application of machine learning techniques to integrate genetic, epigenetic, metabolomic, and proteomic data associated with substance use trajectories offers new opportunities for development of these biomarkers. In addition, All of Us biospecimens, along with linked survey and electronic health records data; as well contextual data from outside sources, can advance research on clinical epidemiology, prevention and care at the intersection of substance use and co-occurring conditions such as HIV and Hepatitis C Virus (HCV).

The All of Us cohort provides a unique opportunity to investigate biological, environmental, and behavioral factors that influence communication and sensory health. NIDCD is interested in applications that use All of Us biospecimens and data resources to advance research across NIDCD mission areas and support precision medicine approaches.

Areas of interest include, but are not limited to:

• multiomic studies of sensory and communication function and disease mechanisms;
• identification of biomarkers associated with risk, diagnosis, prognosis, disease stratification, or treatment response;
• integration of newly generated molecular data with existing All of Us resources; and
• identification of clinically relevant subpopulations to improve prevention, diagnosis, or treatment of communication and sensory disorders

In the context of this topic, NIDCR encourages investigator-initiated research that aligns with the objectives of the topic and advances research relevant to dental, oral and craniofacial (DOC) biology, health, and disease. Specifically, multi-omics studies, systems biology, and other data-driven science leveraging multidimensional, scientific data, including Real World Data are encouraged to achieve holistic understanding of DOC mechanisms and interplay of factors in the context of overall health.

NIDDK is interested in the use of All of Us biospecimens to conduct large scale biomarker and omics analysis of common chronic conditions within the NIDDK mission, including diabetes, endocrine and metabolic disease, obesity, liver and gastrointestinal diseases, and kidney, urologic and hematologic diseases. Interests include:

• Generation of multiomic data that can be integrated with existing All of Us data to understand disease etiology, pathophysiologic mechanisms and biological heterogeneities;
• Development of new biomarkers for prediction of: 
  • disease risk, progression, or trajectory;
  • risk for complications; or
  • response to treatment
• Integration and association of multiomic or biomarker data from All of Us samples with phenotype data types relevant to NIDDK diseases, including: 
  • continuous glucose monitoring;
  • diet and nutrition;
  • medication;
  • behavioral and environmental data.

The National Institute of Environmental Health Sciences (NIEHS) is interested in applications that utilize existing All of Us samples and data to advance exposomics and precision environmental health. Environmental exposures of interest include, but are not limited to, air pollutants, pesticides, trace elements, nanomaterials and microplastics, endocrine disrupting chemicals, contaminants of emerging concern, and environmental exposures related to extreme weather or disasters.

Relevant studies include:

• Characterizing environmental exposures and integrating new data into the All of Us Researcher Workbench to advance the understanding of environmental determinants of health and disease 
• Combining genomic and environmental data to enable precision environmental health approaches that can better inform disease susceptibility, mechanisms, and high-risk subpopulations
• Developing or applying novel computational strategies for exposomics research leveraging All of Us data

NIMH is interested in studies that use All of Us biospecimens to accelerate genomic and biospecimen-derived molecular discovery relevant to mental illness.

Area of interest include:

• Studies of genetic and genomic and multi-omic contributions to mental disorders, related illnesses, and traits. 
• Neurodevelopmental disorders (e.g., autism spectrum disorder, intellectual disability), psychotic disorders (e.g., schizophrenia), mood disorders (e.g., bipolar disorder, major depressive disorder), and mental health and neurocognitive complications associated with HIV, as well as post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders, suicidal thoughts and behaviors, and analyses across diagnostic categories.  
• Long-read sequencing, genome-wide methylation profiling, and RNA sequencing technologies, and molecular datasets generated from All of Us biospecimens. 

 Applicants planning projects using peripheral biomarkers are encouraged to contact the NIMH Scientific Contact. 

NIMHD supports solutions-oriented research that advances precision medicine research and reduces health disparities by using existing All of Us biospecimens along with other data domains including EHRs, survey data, physical measurements, and digital health data. Projects must include validated behavioral, clinical, or biomedical outcomes. Priority areas include but are not limited to:

• Analyzing biomarkers to quantify how social and contextual factors alter biological pathways to drive differences in conditions like cardiovascular or metabolic diseases
• Examining biospecimens for environmental biomarkers to understand how geography, built environment, and exposures drive distinct physiological vulnerabilities and disparate health outcomes
• Leveraging wearable data with biospecimens to link objective digital signatures of sleep, heart rate, or physical activity to physiological markers of stress and health

NINDS encourages investigators to explore the All of Us (AoU) Research program data and biospecimens and leverage it to test hypotheses within NINDS mission areas. 

NINDS anticipates that AoU research data and biospecimens may be leveraged to conduct exploratory or confirmatory studies in some of the following research areas:

• Studies using AoU biospecimens to evaluate biomarkers associated with neurological disorders and stroke
• Alzheimer’s disease-related dementias (ADRD), including Frontotemporal degeneration (FTD), Lewy body dementia (LBD), Vascular contributions to cognitive impairment and dementia (VCID), and Multiple-etiology dementias (MED)
• The neural exposome comprises all environmental factors experienced across the lifespan that influence brain health and disease. Analyses of the AoU data to determine how the exposome contributes to neurological disease risk, progression, or resilience. See Neural Exposome Factors that Affect Brain Health and Neurological Disorders.

NINR supports rigorous, solutions-oriented research that uses multilevel approaches to promote health and prevent disease. Among NINR’s research priorities are addressing health differences, chronic disease prevention, and implementation science focused on clinical and community health outcomes. NINR encourages community-partnered research approaches to ensure that scientific discoveries work in the real world. 

NINR recognizes that the All of Us biobank offers unique opportunities to understand how biological factors interact with the conditions of people's lives to influence health outcomes. For this topic, NINR is particularly interested in research that advances understanding of the interplay between biological, behavioral, social, and environmental factors that influence health and well-being across the lifespan. Research conducted by scientists from any discipline is welcome.

NLM is interested in investigator-initiated applications that leverage already-collected All of Us biospecimens to develop, evaluate, and disseminate biomedical informatics and data science methods, tools, and resources that advance NLM’s mission.

Areas of interest include, but are not limited to: 
             

• Use of All of Us biospecimen-derived molecular data to enable broadly applicable informatics innovation, including trustworthy and reproducible AI
• Scalable data integration, benchmarking frameworks, and interoperable tools
• Freely available end-products, such as software, pipelines, standards, metadata schemas, benchmarks, and evaluation frameworks
• Methods and resources designed to generalize to comparable datasets and settings beyond All of Us

ORWH, in partnership with NIH ICOs, supports use of All of Us biospecimens to advance precision medicine research relevant to women’s health across the life course. 

Areas of interest: 

• Biomarker and multiomic studies of sex-related biological influences to improve understanding of disease risk, diagnosis, and prognosis, and disease stratification 
• Studies supporting the production, curation, and analysis of biomarkers and multiomic data of conditions that uniquely, disproportionately, or differentially affect women across the life course 

In conjunction with collaborating ICs, the Office of Autoimmune Disease Research in ORWH is interested in supporting research seeking to leverage All of Us Research Program biospecimens for:  

• Studying fundamental mechanisms of autoimmunity and autoimmune disease  
• Investigating drivers of autoimmune disease signs, symptoms, and flares 
• Researching co-occurring and co-morbid conditions