It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

The purpose of this FOA is to invite applications for the Artificial Intelligence for Multimodal Data Modeling and Bioinformatics (AIMDMB) Center as part of the Nutrition for Precision Health consortium. The overall goals of the AIMDMB Center are to develop comprehensive dietary intervention algorithms that can predict biological responses to a myriad of input data, and to enable adaptive visualization and interrogation of multimodal data with advanced mathematical and computer modeling tools, Examples of such advanced tools and techniques include, but are not limited to in silico human dietary response replicates or digital twins (e.g., user-tailored, high-fidelity models that incorporate environmental, behavioral, multi-omic, social, clinical or other data to predict health trajectories). These tools would be utilized by researchers to understand nutritional perturbations at the individual to population level as well longitudinal dynamics of human health, and subsequent transition to disease, by way of nutritional patterns.

This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress.

Applicants responding to this FOA are expected to familiarize themselves with the five other companion FOAs listed below since the AIMDMB will be expected to communicate, coordinate, and collaborate with the awarded components of these FOAs.

Companion FOAs of the Nutrition for Precision Health Consortium

• RFA-RM-21-002: Nutrition for Precision Health, powered by the All of Us Research Program: Metabolomics and Clinical Assay Center (U24 Clinical Trial Not Allowed). A Metabolomics and Clinical Assays Center will perform metabolomics analyses and other clinical assays on biospecimens.
• RFA-RM-21-003: Nutrition for Precision Health, powered by the All of Us Research Program: Microbiome and Metagenomics Center (U24 Clinical Trial Not Allowed). A Microbiome and Metagenomics Center will perform microbiome, metagenomics and metatranscriptomics analyses on stool samples for all participants.
• RFA-RM-21-004: Nutrition for Precision Health, powered by the All of Us Research Program: Dietary Assessment Center (U24 Clinical Trial Not Allowed). A Dietary Assessment Center will apply at least two innovative approaches to assess dietary intake in all participants, and improve these methodologies through validation, evaluation, and modeling efforts with data from free-living and controlled feeding studies.
• RFA-RM-21-005: Nutrition for Precision Health, powered by the All of Us Research Program: Clinical Centers (UG1 Clinical Trial Required). Clinical Centers will engage, consent, and enroll participants from All of Us and conduct 3 diet modules (usual dietary assessment, a controlled feeding dietary intervention and a domiciled dietary intervention).
• RFA-RM-21-006: Nutrition for Precision Health, powered by the All of Us Research Program: Research Coordinating Center (U24 Clinical Trial Not Allowed). The Overall study coordination and data management (this FOA) will be provided by a Research Coordinating Center (RCC).

The set of six companion FOAs and existing All of Us Research Program components will establish the Nutrition for Precision Health consortium.

AIMDMB Center: Artificial Intelligence for Multimodal Data Modeling and Bioinformatics Center

DAC: Dietary Assessment Center

DRC: Data Research Center

NPH: Nutrition for Precision Health

RCC: Research Coordinating Center

Background

Strategic plan for NIH Nutrition Research

The 2020-2030 Strategic Plan for NIH Nutrition Research was released in 2020 and will guide NIH-supported nutrition research over the next decade. The Plan was organized around a unifying vision of precision nutrition research.

Research is needed to provide more precise and dynamic nutritional recommendations than currently possible through population-wide guidance. This in turn will facilitate a deeper understanding of how human biological systems and molecular pathways interact with or mediate the relationships among dietary patterns, environmental, social, and behavioral factors to influence health status. Through advances in -omic technologies and mobile devices combined with the large and diverse participant sample and existing infrastructure of theAll of UsResearch Program, innovations in artificial intelligence, machine learning, computational and mathematical modeling of complex biological systems an unprecedented opportunity exists currently to predict dietary responses and to design targeted dietary interventions aimed at improving health and quality of life.

The goal of the Nutrition for Precision Health, powered by the All of Us Research Program consortium (referred to as Nutrition for Precision Health in this document) is to develop algorithms that predict individual responses to foods and dietary patterns.

Nutrition for Precision Health, powered by the All of Us Research Program

Enrollment: Nutrition for Precision Health will enroll current All of Us participants through targeted enrollment. All of Us participants will not be required to participate in Nutrition for Precision Health, and a participant s decision whether or not to enroll in Nutrition for Precision Health will not affect the participant’s status as an All of Us participant. Nutrition for Precision Health will use a separate enrollment process from the All of Us Research Program, and, in order for a participant to enroll in Nutrition for Precision Health, they must already be enrolled in All of Us.

Data Collection, Generation and Integration: All data from the Nutrition for Precision Health study will ultimately be deposited in the All of Us Researcher Workbench, where it will be integrated with All of Us-collected data, analyzed by Nutrition for Precision Health researchers, and made available for use by the scientific community. Data will be generated and collected by the Clinical Centers, Dietary Assessment Center, Microbiome and Metagenomics Center, and Metabolomics and Clinical Assays Center. These Centers will send raw and processed data to the Research Coordinating Center for further curation and processing. The Research Coordinating Center will coordinate with the All of Us Data and Research Center to deposit the data into the Researcher Workbench. Nutrition for Precision Health investigators, including the AIMDMB Center, will access and work with Nutrition for Precision Health data in the Researcher Workbench. By leveraging existing data collection approaches, metadata standards, APIs, and other tools compatible with the Common Fund Data Ecosystem (CFDE; https://commonfund.nih.gov/dataecosystem), the Nutrition for Precision Health consortium will facilitate interoperability of Nutrition for Precision Health data with other large NIH datasets and interrogation across datasets (e.g., by using the CFDE workspaces), as allowed by data protection status.

Modular Discovery Science: Nutrition for Precision Health is a modular discovery science study.

• Module 1 will follow approximately 10,000 participants for up to 14 days to examine baseline diet and physiological responses to test meal challenges. Module 1 is anticipated to consist of two clinic visits approximately two weeks apart, with remote data collection during the study period.
• Module 2 is expected to be a free-living controlled feeding study that will examine responses to three short-term (~14 days) intervention diets in approximately 1,500-2,000 Module 1 participants. Additionally, after each intervention diet, physiological responses to the test meal will be assessed.
• Module 3 is expected to be a domiciled controlled feeding study that will examine responses to the same three short-term (~14 days) intervention diets in approximately 500-1,000 participants from Module 1. Additionally, after each intervention diet, physiological responses to the test meal will be assessed.

In all 3 modules, investigators will collect dietary, microbiome, physiological, metabolic, behavioral, cognitive, environmental, social, demographic, cultural, and contextual data, and leverage standard All of Us-collected genomic, electronic health, and survey data to model the impact of diet and dietary patterns on physiological responses.

All Nutrition for Precision Health awardees must work collaboratively to plan and execute a large precision nutrition study that will catalyze precision nutrition research in transforming the application of targeted dietary approaches to improve health and reduce chronic diseases. The product will be predictive algorithms that inform targeted dietary approaches.

This project will be embedded in the All of Us Research Program and will enroll existing All of Us participants. The All of Us Research Program is guided by a set of Core Values that will also guide the Nutrition for Precision Health consortium.

The goal for the field of precision nutrition, a subset of precision medicine, is to provide more precise and dynamic nutritional recommendations than currently possible through population-wide guidance. To advance this field, research is needed to achieve a deeper understanding of the interplay of human biological systems with the wide variety of factors known to underlie interindividual differences in dietary responses. Individual differences in genetics, epigenetics, microbiome ecologies, biology, nutritional status, behaviors, environments, and socioeconomic influences and disparities may influence these interrelationships. Progress in development of new large data sets and advanced methods for mining them offer an opportunity for precision nutrition to advance its goal.

New advances in data science, including approaches to the description, collection, storage, integration, and analysis of large, heterogeneous, structured and unstructured data sets, as well as new computational methods utilized for analysis and prediction probability (e.g., machine learning, deep learning, and artificial intelligence - AI) are expected to transform biomedical and behavioral research and lead to improved health for individuals to populations. These advances offer biomedical research the ability to computationally make predictions based on data (e.g., probability projections of multiple outcome trajectories). For example, AI can be applied to -omic data, imaging data, traditional data collection systems (e.g., electronic medical records, national health systems, surveillance, surveys) and/or other contextual metadata for machine-assisted learning and prediction from diverse, high-content data. AI can be used for both the prerequisite integration of multimodal data as well as for the modeling and predictive output. Most recent progress in AI for biomedical applications has been restricted to well-defined tasks not requiring integration of data across multiple modalities. For example, clinical successes have been achieved for digital pathology and radiomics. Although, the impact of AI for the biomedical sciences has been constrained by the availability of appropriate training and benchmarking datasets (e.g., bias, noise, sample size, sharing/acquisition policies, data complexity, and protected health information/personal identifiable information protection) as the predictive value of the AI-generated models are only as valuable as the input data. This presents a challenge to realizing the primary benefit of AI in the biomedical sciences (e.g., predictive analytics from the totality of medical evidence) as human health, and subsequent transition to disease, occuras a longitudinal set of perturbations over the course of life, requiring context (e.g., diet, past medical history, -omics, laboratory results, health disparities, social and behavioral determinants).

Nutrition for Precision Health aims to overcome past nutrition barriers in order to acquire signatures of human health with respect to nutrition. This begins with the generation of multimodal, metadata-complete, human data sets that exemplify adherence to specific rubrics from a large sub-population of All of Us Research Program participants. Thus, offering appropriate sample size as well as consistent data provenance and quality from both data collection and measurement, these data sets will enable AI-based informatics tools to be trained and ultimately utilized for understanding human health with respect to nutrition, and other elements that play a role, in the transition to disease. Furthermore, a prospective analysis of signatures of health and nutritional intake will enable tools that facilitate more effective decision making by individuals and their nutritional intake.

This FOA invites researchers to submit applications as to the development of robust and artificially intelligent informatics platforms to model and interrogate multimodal, metadata-complete, human data sets from the Nutrition for Precision Health consortium. With the ultimate goal of producing algorithms that predict individual responses to foods and dietary patterns, the proposed AIMDMB Center projects will develop a suite of computational tools to perform data integration, harmonization, analysis and visualization of the multi-modal and multi-fidelity data as well as incorporate an adaptive design for future data incorporation, while within the All of Us Researcher Workbench. The AIMDMB Center will generate actively learning algorithms to predict human biological response to different foods, nutrients, food components, and dietary patterns as well as advance understanding, from the individual and population level, of longitudinal dynamics from multimodal data with advanced mathematical and computer modeling tools (e.g., with in silico human dietary response replicates or user-tailored, high-fidelity models that incorporate environmental, behavioral, multi-omic, social, clinical or other data to predict health trajectories). The proposed AIMDMB Center will be a hub in communicating state of the art for AI-ready' biomedical data (e.g., well-annotated metadata, requisite sample size and data granularity, data provenance, multimodal data dynamics and curation needs) to Nutrition for Precision Health and be a hub of discovery from artificial intelligence for biomedical research excellence.

Research Objectives and Scope

The objective of this FOA is to enable AI-assisted learning, visualization and, ultimately, prediction from diverse, longitudinal data acquired from both non-targeted -omic data (e.g., genomics, epigenomics, proteomics, metabolomics, transcriptomics, metagenomics) as well as other targeted inputs (e.g., continuous or discontinuous metabolic, endocrinologic, physiological, wearable device data, cognitive and behavioral measures, surveys, questionnaires, electronic health records, data from social media apps and, and community/environmental data). Although diversity of data types will be broad, the measurement methods and provenance will be consistent, furthermore, will be acquired from a large sample size representative of the U.S. population. A goal for the Center will be to leverage multidisciplinary approaches and technologies, including advanced computing, predictive computational modeling and AI, to derive new knowledge and generate hypotheses through active learning for precision nutrition.

The scope of this FOA covers data integration, informatics technology, and software development for multimodal data from the Nutrition for Precision Health consortium in the All of Us Researcher Workbench, as well as AI-guided data integration, modeling and prediction. As such, the AIMDMB Center should consist of a set of projects and cores that can synergistically work in tandem and with the Nutrition for Precision Health consortium to deliver both platform technologies as well as scientific discovery from biomedical data. Applicants are required to develop multidisciplinary (e.g., biomedical data science, bioinformatics, clinical/health informatics, biostatistics, machine learning, artificial intelligence, nutrition, -omics, or other biological and physical sciences) expertise and encouraged to have multisector (e.g., public, private, non-profit, or government collaborations) teams to lead and perform the AIMDMB Center research and development efforts. While innovative new solutions are encouraged, so is building upon existing open-source community tools or projects. It is also critical, to maintain flexibility and innovation both in the types of data science research undertaken during the course of this project as well as software engineering approaches that will be adopted. A key consideration is that Nutrition for Precision Health data will be deposited and shared in the All of Us Research Program s Researcher Workbench (https://www.researchallofus.org/workbench/); it is important to pursue technological and computational strategies that enable acceptable and facile data flow with the Researcher Workbench.

Potential Areas of Research

While the specific area(s) the AIMDMB Center application proposes to address will be determined by the applicant, potential topics, especially in the context of the needs for the broader Nutrition for Precision Health consortium, that should be considered include, but are not limited to:

• Development of methods and protocols to seamlessly integrate multimodal data into a common framework for processing and computer modeling;
• Development of a modular data integration workflow, data and analytic standards, harmonization protocols, and defining requirements for AI-ready data to guide development of predictive algorithms for the Nutrition for Precision Health consortium as well as future biomedical researchers;
• Development of computational tools to perform data analyses, integration, harmonization, and modeling of multi-modal and multi-fidelity data. These tools could allow for quality control with respect to data provenance, facile adaptation for incorporation of other data types (e.g., data agnostic), and evolving data standards;
• Development or expansion of informatic tools and statistical methodologies to analyze multi-dimensional -omics data, behavioral data, and related complex data;
• Development and use of shared platforms for leveraging of large health datasets that enable discovery of emergent patterns of human health (especially in the context of nutrition or dietary patterns) as well as longitudinal risk;
• Data-driven and computational approaches for examining developmental trajectories of nutrition, health and subsequent transition to disease (including disparities, life-course patterns, and/or generational differences);
• Development of adaptive, transparent, and mechanism-based computationally-enabled modeling algorithms to specific questions or problems identified and prioritized by the Nutrition for Precision Health consortium. This could take place during initial or in subsequent years and can be addressed with pilot projects built into the Administration and Coordination Core (see below);
• Data science technologies and approaches for behavioral health interventions that leverage novel data sources, wearable devices and smart phone applications, new and emerging sensors, and emerging machine learning approaches;
• Development of multimodal data presentation and visualization platform(s) that allows in silico human dietary response replicates or digital twins (e.g., user-tailored, high-fidelity models that incorporate environmental, behavioral, multi-omic, social, clinical or other data to predict health trajectories) for Nutrition for Precision Health and other stakeholders. These tools could allow for data input from retrospective data (e.g., from natural history studies) and a predictive analytical output or trajectory across cohort populations, sub-populations, and individual level; and
• Development of adaptive, ethical, unbiased (e.g., representative of the U.S. population), transparent, and mechanism-based computationally-enabled modeling algorithms to:
• predict biological response to different foods, nutrients, food components, dietary patterns using all available study data across cohort population, sub-populations, and at the individual level;
• predict human health outcomes by way of nutritional or behavioral patterns with respect to multi-omics (e.g., genomics, epigenomics, transcriptomics, epitranscriptomics, proteomics, or other biomarkers) to advance applied research efforts in the development of polygenic risk scores;
• improve methods (or develop correction factors) to improve dietary assessment with respect to energy expenditure (e.g., room calorimetry or doubly labeled water); and
• monitor, prevent, and/or reduce nutritional health disparities originating from novel algorithm design, selection of training datasets, and communication and information dissemination across diverse populations.

Team Expertise

To address the goals of this FOA, the team of the proposed AIMDMB Center could include, although not limited to, the following group / types of experts:

Expertise in biomedical data science, bioinformatics, clinical / health informatics, and/or machine learning / artificial intelligence;

Expertise in nutrition science, intermediary metabolism, and / or physiology;

Expertise in advanced computational and data analysis approaches (or biostatistics necessary to support data efforts), and software platform development.

AIMDMB Center Structure

Each Artificial Intelligence for Multimodal Data Modeling and Bioinformatics (AIMDMB) Center should contain several interconnected structural/functional units:

• Administration and Coordination Core (required, maximum of one);
• AIMDMB Research Projects (required, minimum of two; maximum of four);
• AIMDMB Data Management and Analysis Core (required, maximum of one); and,
• AIMDMB Shared Resource Cores (optional).

Administration and Coordination Core: Given the need for integration of multidisciplinary efforts in the AIMDMB Center, the scientific leadership and other senior members of the team are expected to have considerable experience in collaborative, multidisciplinary research and development relevant to the goals of the AIMDMB. The Center must organize an Administrative and Coordination Core to facilitate effort coordination and support the operation of the Center. This core leads the projects/cores, maintains the organization of the Center (and its external collaborations), and ensures that the projects and cores are being supported to achieve the AIMDMB Center goals. The Administrative Core facilitates and coordinates communication of results, accomplishments, and implications of the AIMDMB Center research to stakeholders, including appropriate NIH staff, the Nutrition for Precision Health consortium's Research Coordinating Center (RCC), Nutrition for Precision Health consortium's Steering Committee, and other stakeholders in a context that makes the research applicable to the target audiences. The Administrative Core has the critical role in assisting project/core leaders in translating their research outcomes and activities to appropriate audiences (including industry partners for applicable commercialization of AIMDMB Center-related innovations); ensuring the accurate and timely use of products and sharing of findings; and advancing appropriate ethical, legal, and social implications of research tied to research projects. This core also has the primary role of initiating partnerships, arranging appropriate subawards, determining and distributing award funds, etc. as partnerships expand over the course of the award. It is anticipated that an iterative cycle of both technological and intellectual development flowing between the AIMDMB and other components of the Nutrition for Precision Health consortium (including components of the All of Us Research Program) will be coordinated by the Administration and Coordination Core of the AIMDMB Center to ensure a continued engagement by all parties and that this will escalate in sophistication over the project period.

Additionally, a key component of the Administrative and Coordination Core must involve a mechanism to provide sub-award support for pilot projects that have significant potential to address developing needs and opportunities while being shorter term and varying throughout the period of award. These pilot projects will allow the AIMDMB Center and the broader Nutrition for Precision Health consortium to take advantage of new directions stimulated by the evolving needs and science. Further, to form new partnerships, provide support to early-stage investigators to undertake data science-related research and innovation in or related to nutritional science, and support relevant cross-consortium projects. For example, these projects could include: optimization of data platforms developed by other Nutrition for Precision Health consortium components, AI grand challenges or 'hackathons' to drive algorithm development, focus on elements that were not originally proposed by AIMDMB Center yet are needed from the evolving nature of the broader consortium, etc. The pilot projects will be initiated by way of the collective decision, as to their focus and needs, from the Nutrition for Precision Health consortium's Steering Committee. It is expected that the AIMDMB Administrative and Coordination Core will establish and manage a solicitation, review, and selection process for collaborative sub-award pilot projects, including the distribution of yearly sub-award funds. AIMDMB Centers are required to fund a minimum of one sub-award project per year and allocate a minimum of $250K per year direct costs, beginning in Year 2 of the research funding cycle.

AIMDMB Research Projects: A set of two to four individual Research Projects are required for each AIMDMB Center. These projects should be synergistic to represent an integrated research program and support the overarching goals for both the Center and the Nutrition for Precision Health consortium. One research project must be solution-oriented through the development or adaptation of a product (software or hardware) or new technology that is needed for the collection of new data within the consortium. Other research projects proposed will be up to the applicants to define relative to the needs outlined above and the investigator-initiated ideas as to how to build the Center for delivering the needs for the Nutrition for Precision Health consortium. Projects should primarily focus on use of data that will be obtained during the Nutrition for Precision Health study and with respect to the Consortium Data Workflow (see below). Research Projects may be supported by optional Shared Resources Core(s).

AIMDMB Data Management and Analysis Core: Data represent important research products and attention is needed to provide for its stewardship and to treat it as an asset. To promote best practices and support NIH data sharing policies (https://grants.nih.gov/policy/sharing.htm), the AIMDMB Center must have one Data Management and Analysis Core (DMAC). The primary purpose of the DMAC is to support the management, integration, and interoperability (as appropriate) of data assets across the Center, including research projects and all pilot projects, and ensuring interoperability and compatibility of APIs and other tools with the Common Fund Data Ecosystem. The DMAC will support management and analysis of both pre-existing data used by the Center and new data produced through the Nutrition for Precision Health consortium, as well as the development of tools for data assessment. Developing creative approaches that foster the development or strengthening of artificial intelligence ready data sets (AI-Ready) is desired. The DMAC should also establish, coordinate, and monitor processes for data analysis and work closely with project (and core) leaders to ensure high data quality throughout the entire lifecycle of the data. The DMAC also has a coordinating role to work with project/core leaders to identify opportunities for integrating Nutrition for Precision Health consortium data with other existing datasets, as appropriate. Importantly, the AIMDMB DMAC will ensure that algorithms are developed and trained from ethical and unbiased data sets (e.g., inclusive of racial and ethnic minorities, geographic area, and other health disparities). It is anticipated that data from the Nutrition for Precision Health consortium study will be collected across a broad cohort that is representative of the U.S. population.

Consortium Data Workflow

It is expected that the platforms, tools, algorithms or other to be developed by an AIMDMB Center will include a distinctive and integrated combination of them, as appropriate to the above objectives and scope. These are anticipated to be built within the framework of the AIMDMB Center with respect to the Nutrition for Precision Health consortium's data workflow.

Nutrition for Precision Health Consortium Formation and Governance

The award(s) funded under this FOA will be a cooperative agreement (s). Close interactions amongst the awardee, awardees from the companion FOAs, awardees from existing All of Us components (Biobank, Data and Research Center, and Participant Technology Systems Center), and NIH staff will be required. Shortly after the award, the PDs/PIs and NIH program staff will form the Nutrition for Precision Health Steering Committee. One PD/PI per award and select NIH staff will be voting members of the Steering Committee. Consortium governance rests with the Steering Committee and is subject to oversight by an NIH Nutrition for Precision Working Group of the NIH Common Fund, which will include NIH representatives from the All of Us Research Program.

The NIH will appoint co-chairs of the Steering Committee from among the Nutrition for Precision Health PDs/PIs. The Steering Committee Co-Chairs will preside at all Steering Committee meetings and serve on an Executive Committee. The Executive Committee will assist as necessary with annual progress reports and appoint and charge members of subcommittees. These subcommittees will facilitate development, implementation, and monitoring of specific Nutrition for Precision Health functions/activities as needed, such as recruitment and retention, participant engagement, biospecimen quality control, and publications and presentations. Representatives from various components of Nutrition for Precision Health consortium will be expected to serve on subcommittees as appropriate according to their expertise.

The Steering Committee will meet in person in Bethesda, Maryland twice during the first year and at least annually thereafter. Monthly teleconferences will be held for the Steering Committee and its subcommittees, and these may be more frequent at times to facilitate planning, etc. The RCC will be responsible for organizing and facilitating the meetings and teleconferences. Applicants should plan to attend an initial planning meeting of the Steering Committee in Bethesda, Maryland, to be held within 4 months of the initial award.

The Steering Committee will have responsibility for developing the overall scientific direction of the program, setting the policies and procedures for the governance of the program, assuring compliance with these program policies and procedures, designing study protocols, implementing studies, ensuring data quality and completeness, planning for analysis and interpretation of data, developing data sharing policies and reporting results in presentations and publications. The Steering Committee must work cooperatively and interactively during the first year to develop the final protocols and the materials necessary to begin the study twelve months after award. The final plan, with a study timeline and milestones, will be submitted for the consideration of the NIH Nutrition for Precision Health Working Group and the NIH Division of Program Coordination, Planning, and Strategic Initiatives (DPCPSI) before the second year of funds will be awarded.

First year planning activities for all consortium components include, but are not limited to:

• Developing consortium committees, policies, and procedures for the smooth governance of the Steering Committee;
• Developing a detailed plan for enrollment of participants according to All of Us diversity goals;
• Developing protocols and plans for the assessment of physiologic, metabolic, behavioral, environmental, contextual, dietary, and other phenotyping of participants;
• Developing a plan to support study participants, clinical staff, and other study staff by facilitating and developing training materials and videos and providing staffing for help lines (staffed by dietitians) related to mobile technologies and dietary assessment; Standardizing measures and surveys;
• Refining inclusion/exclusion criteria and sample size;
• Determining numbers and timing of biospecimen collection from participants;
• Overseeing plans to address the various bio-ethical issues and concerns (e.g., handling of sensitive data, participatory risk, involvement of vulnerable populations, incidental findings) that are likely to arise during the conduct of the research;
• Obtaining approvals as needed at the consortium Site institutions, such as IRB approval;
• Preparing a Manual of Operations with primary responsibility residing with the RCC;
• Developing a detailed plan for storage and shipping of all biospecimens;
• Developing detailed plans for the thorough analysis of biospecimens collected in the Clinical Centers, including metagenomics, meta-transcriptomics, and metabolomics. This includes deciding which tissues will be analyzed by each method and adjusting these decisions as results and technologies become available;
• Planning for data standards, anonymization, assembly, curation, provenance, access, analysis, and storage;
• Planning for deposition of data into the All of Us Researcher Workbench to ensure data access to the broader scientific community;
• Planning for return of results to All of Us participants; and
• Developing a detailed timeline with concrete milestones for the entire study.

As the Nutrition for Precision Health study data will begin to be available by the second year, additional planning activities specific to the AIMDMB Center could include:

• Collaboration with the All of Us Research Program to develop transparent, ethical protocols and procedures for working with study data within the All of Us Researcher Workbench;
• Collaborating with other NIH Common Data Framework efforts for artificial intelligence in biomedical research (for example, NIH Bridge to Artificial Intelligence (Bridge2AI)) or other federal agency efforts (for example, the National Institute of Standards and Technology (NIST)) to guide future data standards and defining AI-Ready requirements;
• Development of adaptive, transparent, and mechanism-based computationally-enabled modeling algorithms to specific questions or problems identified and prioritized by the Nutrition for Precision Health consortium. This would take place during initial year or in subsequent years; and
• If needed to help drive development of platform technologies as well as successful completion of project(s) aims, leveraging existing relevant data sets of sufficient similarity (e.g., All of Us, or other), to guide and / or optimize Center’s informatic platform development, data integration, algorithm development or data visualization tools prior to study data delivery

External Study Monitoring

Four to six External Program Consultants will provide input based on their individual areas of expertise as needed over the course of the program. They will assist the NIH Nutrition for Precision Health Working Group regarding processes and substantive issues that arise during the project and will help ensure that the resources to be delivered by the program are as useful as possible for the end users.

An independent Data and Safety Monitoring Board (DSMB) will be established to monitor and provide recommendations to the NIH regarding participant engagement/enrollment, safety, data quality, and other issues, as appropriate. The DSMB will also review the Steering Committee-approved common protocol, informed consent templates, milestones, and monitoring plans prior to the start of enrollment. A single central Institutional Review Board (IRB) should be used to streamline the protocol approval process and to standardize the monitoring of human subjects protection in Nutrition for Precision Health. The RCC will be responsible for developing and finalizing the Data and Safety Monitoring Plan and for managing DSMB and IRB logistics.

Common Fund Data Ecosystem

The NIH Common Fund (CF) programs are intended to provide resources that accelerate discovery across many different biomedical research fields. These resources include large data sets and associated digital tools needed to mine and analyze the data. To maximize their impact, data sets and tools generated by the CF programs must be usable together. Towards achieving this goal, the Common Fund created the Common Fund Data Ecosystem (CFDE), a data management infrastructure where the interconnected ecosystem facilitates scientific advances by ensuring CF data and digital objects are usable and useful both within a program and in combination with data from other programs. Aims of the CFDE are to enhance the ability to ask scientific questions; enable the uptake, reuse, and addition of data sets generated by the future, current and ended CF programs and support their sustainability; and provide training that maximizes scientists ability to use the CF data sets and tools. The CFDE is composed of a CFDE Coordination Center (CFDE-CC) and the data coordinating centers (DCCs) of the participating CF Programs. CFDE teams will work towards standardizing the data deposition/structuring/handling to make data FAIR, adapting data and metadata standards to enable interoperability, and providing training about the available CF resources to the scientific community.

New CF programs (e.g., Nutrition for Precision Health) are expected to engage in the CFDE from the start. This can be achieved by designing the program components such that they: i) construct a data infrastructure which ensures FAIRness of the data, and ii) adapt the appropriate data and metadata standards to enable interoperability of the generated data with other data sets. The Nutrition for Precision Health Research Coordinating Center will be the primary point of contact with the CFDE. Applicants are expected to discuss their plans for ensuring compatibility with the CFDE and other Common Fund datasets and resources (e.g., via the CFDE portal, Metabolomics Workbench and the MoTrPAC Data Hub) in their application.

Leveraging STRIDES for Cloud Computing Activities

The NIH Science and Technology Research Infrastructure for Discovery, Experimentation, and .Sustainability (STRIDES) initiative has established partnerships with commercial cloud service providers (CSPs) Google and Amazon Web Services (AWS) to provide favorable pricing for cloud-based costs. The NIH Common Fund, managed by the Office of Strategic Coordination, is using the STRIDES partnerships to provide in-kind support for CSP costs. For more details, please see NOT-RM-20-009.

IMPORTANT NOTE: Researchers uncertain as to whether their intended framework for a AIMDMBC Center meets the requirements of this FOA are encouraged to contact NCI scientific staff listed in Section VII. Agency Contacts.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government, including NIH Intramural Program
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.

Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) Applicants must complete and maintain an active registration, which requires renewal at least annually. The renewal process may require as much time as the initial registration. SAM registration includes the assignment of a Commercial and Government Entity (CAGE) Code for domestic organizations which have not already been assigned a CAGE Code.
• o NATO Commercial and Government Entity (NCAGE) Code Foreign organizations must obtain an NCAGE code (in lieu of a CAGE code) in order to register in SAM.
• eRA Commons - Applicants must have an active DUNS number to register in eRA Commons. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration, but all registrations must be in place by time of submission. eRA Commons requires organizations to identify at least one Signing Official (SO) and at least one Program Director/Principal Investigator (PD/PI) account in order to submit an application.
• Grants.gov Applicants must have an active DUNS number and SAM registration in order to complete the Grants.gov registration.

Program Directors/Principal Investigators (PD(s)/PI(s))

All PD(s)/PI(s) must have an eRA Commons account. PD(s)/PI(s) should work with their organizational officials to either create a new account or to affiliate their existing account with the applicant organization in eRA Commons.If the PD/PI is also the organizational Signing Official, they must have two distinct eRA Commons accounts, one for each role. Obtaining an eRA Commons account can take up to 2 weeks.

Any individual(s) with the skills, knowledge, and resources necessary to carry out the proposed research as the Program Director(s)/Principal Investigator(s) (PD(s)/PI(s)) is invited to work with his/her organization to develop an application for support. Individuals from underrepresented racial and ethnic groups as well as individuals with disabilities are always encouraged to apply for NIH support.

For institutions/organizations proposing multiple PDs/PIs, visit the Multiple Program Director/Principal Investigator Policy and submission details in the Senior/Key Person Profile (Expanded) Component of the SF424 (R&R) Application Guide.

In view of the goals for this FOA, applicants should assemble a multi-disciplinary team with expertise in biomedical data science, systems biology, artificial intelligence, and nutrition as well as other biological and physical science expertise, if viewed as necessary to facilitating a successful outcome when preparing the application and as outlined in Section I.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.

Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:

• A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission (A1) application.
• A resubmission (A1) application that is submitted before issuance of the summary statement from the review of the previous new (A0) application.
• An application that has substantial overlap with another application pending appeal of initial peer review (see NOT-OD-11-101).

Any individual designated as a PD/PI must not be designated as a PD/PI on another AIMDMB Center application.

The application forms package specific to this opportunity must be accessed through ASSIST or an institutional system-to-system solution. A button to apply using ASSIST is available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Multi-Project (M) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Email: [email protected]

Available Component Types	Research Strategy/Program Plan Page Limits
Overall	12
Admin Core (use for "Administration and Coordination Core)	6
Core (use for AIMDMB Data Management and Analysis Core and, if any, Shared Resource Core(s))	6
Project (use for AIMDMB Research Project)	12

Additional page limits described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide, and should be used for preparing a multi-component application.

The application should consist of the following components:

• Overall: required
• Administration and Coordination Core: required; maximum of one
• AIMDMB Data Management and Analysis Core: required; maximum of one
• AIMDMB Shared Resource Core(s): optional; maximum two allowed
• AIMDMB Research Project(s): required; minimum of two; maximum of four projects allowed

When preparing your application, use Component Type Overall .

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete entire form.

Note: Human Embryonic Stem Cell lines from other components should be repeated in cell line table in Overall component.

Follow standard instructions. with the following modifications:

Project Summary/Abstract: For the Overall Component, applicants must provide overall goals/abstract/summary for the entire AIMDMB Center application. The Project Summary should provide an overall indication of the proposed methods and science as to what is proposed to accomplish. For example, the summary should describe research approaches, data science methodologies, available infrastructure, new data required to answer research questions, technology development, etc. In addition, the summary should highlight aspects of the application that are particularly innovative or paradigm-shifting. The primary activities of the cores should be integrated into the summary. The benefits of the AIMDMB Center (in terms of improving healthcare or public health through data science and innovation) should also be included. Note: the project summary should be written in plain language for a diverse set of reviewers while providing a depth of understanding of the science and activities of the AIMDMB Center application.

Project Narrative: In the "Project Narrative", the relevance of the AIMDMB Center research and platform development to the Nutrition for Precision Health consortium in terms of: nutrition research, biomedical data science, and public health should be stated in lay language.

Facilities & Other Resources: In addition to standard items, describe existing facilities and/or other resources (such as existing institutional shared resource cores) available to the proposed AIMDMB Center. As applicable and pertinent to the proposed research, describe partnerships (e.g., U.S. government agency, private sector, non-profit, or academic shared resource collaborations) that will provide relevant capabilities (e.g., technology development, computational expertise, data access to All of Us Research Program's Researcher Workbench, federated database systems, high performance computing, other clinical study data that would be of relevance to the Nutrition for Precision Health study).

Other Attachments: Include attachment named " Previous Platform or Tools Experience." In the attachment, provide a summary documentation for all members of the Center team (preferably in tabular format) to document:

a) Previously developed or used informatics, AI, and biomedical data modeling platforms, tools or software relevant to nutrition research and/or biomedical data science; and

b) any non-nutrition or biomedical data science related informatics, AI, and biomedical data modeling platforms, tools or software previously developed that will be relevant to, and used by, the proposed Center.

Note: This attachment should be formatted as a cumulative summary of informatics, AI, and biomedical data modeling platforms, tools or software for the entire team arranged by aspects a-b listed above. Indicate the institution of technology originators or users as appropriate (e.g., by a column in a table). Justification of the use or need within the project / Center for these items should be saved for the research plan section.

The following item should be included as attachments under Other Attachments.

Consortium Assurance: The filename "Consortium Assurance.pdf" should be used.

The PD/PI should provide a letter stating his/her willingness to participate in Consortium activities, including sharing the scientific portion of the application, participating in meetings at the NIH and regular conference calls and abiding by approved Consortium policies, following all common elements in the protocol agreed to during the planning phase, providing clinical data to the Research Coordinating Center (RCC) in approved formats, and submitting biospecimens for storage at the All of Us Biobank throughout the study. In the letter, the PD/PI may discuss past experiences participating in multi-center studies.

In addition, the PD/PI and an authorized Institutional Official must provide evidence that the Institution is willing to sign a standard reliance agreement and use the single IRB proposed by the RCC, if required, as part of its application, in accordance with NIH policy on the use of a single Institutional Review Board for multi-site research, https://grants.nih.gov/grants/guide/notice-files/NOT-OD-17-076.html.

Enter primary site only.

A summary of Project/Performance Sites in the Overall section of the assembled application image in eRA Commons compiled from data collected in the other components will be generated upon submission.

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application.

Biographical Sketch:

List in sub-section D (Research Support) of biosketches for all key personnel any relevant experiences in operating large multidisciplinary research centers, program projects or other large-scale research endeavors.

A summary of Senior/Key Persons followed by their Biographical Sketches in the Overall section of the assembled application image in eRA Commons will be generated upon submission.

The only budget information included in the Overall component is the Estimated Project Funding section of the SF424 (R&R) Cover.

• Personnel Costs: Senior/Key Personnel and Other Personnel. The request under this category may include estimated costs of salary support (based on level-of-effort) for the PD(s)/PI(s) and other personnel responsible for the various aspects of operation within the functional components of the AIMDMB Center that must be commensurate with the efforts needed for their expected involvement.
• A minimal effort level of 1.8 calendar months for the U54 contact PD/PI; for each project lead the minimal effort is 1.2 calendar months (if both project PI and contact PI then 3.0 calendar months) and core leaders 0.6 calendar months; this effort cannot be reduced below these level during the entire project period.
• Travel: Appropriate travel funds must be included in the proposed budget to support travel for at least one AIMDMB PD/PI to participate in an Annual Steering Committee Meeting.

Applicants who anticipate requiring >$10,000 direct costs in commercial cloud services from either Google or AWS in any one year of the anticipated award are expected to request in-kind support via the Common Fund STRIDES partnerships rather than requesting direct cost support for these services. To request in-kind support for cloud services via STRIDES, applicants must outline the anticipated costs of commercial cloud services in the Budget Justification section, including, but not limited to, data storage, analysis, data movement/egress, professional services, training, and related activities. Please review NOT-RM-20-009 for important details about how to provide this information in your application.

A budget summary in the Overall section of the assembled application image in eRA Commons compiled from detailed budget data collected in the other components will be generated upon submission.

Specific Aims: State concisely the overall vision of the proposed Center. This should not be specific aims of the projects, but should be overarching and at a high level aims / goals / deliverables for the Center. This should highlight the project (and cores or other) and how all components of the Center will work in tandem towards the ultimate goals of both the Center as well as goals of the Nutrition for Precision Health consortium in developing algorithms to predict individual responses to dietary patterns and foods. This should highlight structure and synergy of the Center as well as collaborations to drive both scientific discovery and platform development. This should also highlight any resources that would be leveraged by the Center to amplify the Center impact for the Nutrition for Precision Health consortium beyond the funds awarded.

Research Strategy: The Research Strategy for the Overall component must consist of sub-sections outlined below.

The proposed Center is expected to demonstrate a high level of scientific competence and strong capability for innovation and collaboration. Present the overall vision for the Center, including descriptions of the following:

Center Overview

• Describe the vision of the AIMDMB Center and overall goals;
• Describe the projects/cores in short synopses and their respective aims as well as deliverables. Explain the rationale behind proposed projects (and cores), and how these will collectively:
• develop a suite of computational tools to perform data integration, harmonization, analysis and visualization of the multi-modal and multi-fidelity data as well as incorporate an adaptive design for future data incorporation;
• drive successful development of comprehensive dietary intervention algorithms that can predict biological responses, available energy, and individual health trajectories from multiple types of input data; and
• enable adaptive, predictive algorithms and visualization software / tools for interrogation of Nutrition for Precision Health study, retrospective, or future prospective data for the broader biomedical research community.
• Description of the innovative aspects of the AIMDMB Center should be included. Applicants should describe how the proposed data science-driven approaches lead toward novel solutions for nutritional health barriers or advance understanding of nutrition with respect to Precision Health;
• Description as to how related theoretical concepts, approaches or methodologies, data sets and infrastructure, and/or existing interventions (including novel adaptations of technologies from one field to another) are leveraged;
• Include overall Center milestones addressing how the key goals of the AIMDMB Center will be achieved. A milestone is defined as a scheduled event in the project timeline that signifies the completion of a major project stage or activity. Milestones must be performance-based to enhance the likelihood that the project will be completed on-time and on-budget. In the event of an award, the PD/PI(s) and NIH staff will negotiate the final list of milestones for each year of support. If at any time the project fails to make progress toward meeting milestones (e.g., developing a final protocol and/or manual of procedures including a detailed description of procedures and process details; completing development of platform technologies, etc.), the NIH may consider ending support and negotiating an orderly close-out of the award; and
• Include a timeline that illustrates the AIMDMB Center's vision of how the proposed tools, platforms, approaches, methods, and biological applications relate to one another and the relative target dates for their interactions or intersections.

Significance and Relevance to the Nutrition for Precision Health consortium

• The significance of the proposed research and development in terms of timeliness and potentially transformative outcomes in the context of nutrition research, multi-modal/-scale AI for biomedical data science and the broader biomedical research community. Also, the significance to other ongoing technology development efforts;
• Describe how the projects of the Center will interact to provide a functional, scalable platform and overall philosophy and workflow that will be used to guide the iterative relationship between projects as well as with other members of the Nutrition for Precision Health consortium;
• Describe the strategies to develop transparent, ethical, and unbiased protocols and procedures for working with the Nutrition for Precision Health consortium;
• Describe plans to maximize the impact of the AIMDMB resources by creating an open science framework with rapid data curation and sharing;
• Describe the strategies for adapting to different input data types, new discoveries in the Nutrition for Precision Health consortium, biomedical science, and dividing development among the proposed projects, if needed; and
• Identify the weakest points in the overall platform and propose alternative approaches for these points. Also, issues of data acquisition, data management, data storage, and analytical capability that the AIMDMB Center will confront should be discussed.

Leadership and Center Organization.

• Describe organization of the leadership structure and overall AIMDMB Center structure (provide respective organizational diagrams and include points of intersection, both from synergy and in time for connected milestones / deliverables);
• Outline the major strengths and relevant expertise of research team members and specific senior investigators in the context of the proposed AIMDMB Center (not duplicating information already provided in the Biographical Sketch), and the advantages of their respective research fields for driving successful outcomes for AIMDMB Center and the Nutrition for Precision Health consortium;
• The rationale for inclusion of partnerships (e.g., industrial, foundations) outside of the AIMDMB Center, if any;
• Outline how each of these investigators' groups will be directly involved with and actively contribute to the AIMDMB Center projects, DMAC, and optional AIMDMB Shared Resource Cores (such a relationship is required for each proposed project or core although does not need to be unique for each); and

Describe how the components of the Center, including key personnel, will interact within the AIMDMB Center, why each is essential for accomplishing the overall Center goals, and how the organization of the components into a Center will create an entity that is greater than the sum of its parts in terms of generating results that will be important for the Nutrition for Precision Health consortium as well the broader biomedical data science and biomedical research communities.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. NIH strives to ensure the dissemination of research resources developed with NIH Funds. Detailed Resource Sharing Plans for sharing of intellectual and technological resources is a fundamental aspect of the Nutrition for Precision Health consortium. Resource Sharing Plans should be described here and should be presented as summary of data sharing, management and analysis to be shared. Any proposed sharing plan needs to be consistent with the All of Us Research Program’s data sharing policies (https://allofus.nih.gov/about/core-values).

Further, as it is expected that the algorithms, platform technologies, and / or software the Center has developed, will be further validated and improved through the Nutrition for Precision Health consortium's research. Given the high profile of this study, the PD/PI’s tools could become an important resource that other investigators will want to utilize. While the investigators are expected to substantively participate in this research project, the applicants must develop a resource sharing plan inclusive to all Center projects and cores that explains how the developed resource will be made available to the investigator community in the future including the time course for that plan. The sharing plan may include fees for licensing or use of the tools, but may NOT have reach through agreements , for example that require the involvement of particular investigators in research grant applications, percent effort, future co-authorships or other collaboration requirements. The plan should also minimize administrative impediments to academic sharing of research resources.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

PHS Human Subjects and Clinical Trials Information (Overall)

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, there must be at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record within the application. The study record(s) must be included in the component(s) where the work is being done, unless the same study spans multiple components. To avoid the creation of duplicate study records, a single study record with sufficient information for all involved components must be included in the Overall component when the same study spans multiple components.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).

All instructions in the SF424 (R&R) Application Guide must be followed

All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Admin Core.

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide overall goals/abstract/summary for the Administrative Core.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Personnel: The budget should include a detailed justification for key personnel. The PD/PI or each of the component leads is expected to devote at least 3 person months of his/her efforts to the U54 Center. Salaries for support positions in the U54 Center are permitted. No overlap of time and effort between the U54 Center and other funded projects is permitted.

Supplies: Consumable supplies related to the operation of the U54 Center such as office materials are permitted.

Service Contracts: Service Contracts for major equipment items are allowed.

Consultants: Consultants and any associated costs are permitted.

Pilot program: Budget for the Administration and Coordination Core is required to fund a minimum of one sub-award project per year and allocate a minimum of $250K per year direct costs, beginning in Year 2 of the research funding cycle.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Succinctly describe the list of specific objectives and goals of the Administrative Coordination Core.

Research Strategy: This section will describe the Administration and Coordination Core and should include the following subheadings: Organizational Structure and Staff Responsibilities and Center Outcomes Vision.

Vision Statement of Center Outcomes: This section of the application should entail forward-looking statements about the AIMDMB Center's potential impact beyond the initial award period, addressing all the aspects identified below.

• Describe how anticipated achievements in the performance period would be leveraged to continue major advances in nutrition biomedical data science research and more broadly to public health with national impact;
• Describe plans to facilitate access and broader adoption of technologies developed within the AIMDMB Center award period through academic and/or industrial partnerships;
• Describe how the AIMDMB Center would transition technological and conceptual innovation into future projects and programs (e.g., Program Project Grants, SBIR); and
• Describe the metrics for determining success during the AIMDMB award period and how unanticipated obstacles to the plan may be overcome.

Organizational Structure and Staff Responsibilities:

• Describe and justify the overall structure of the AIMDMB Center and how the PD(s)/PI(s) and the proposed staff will be organized with respect to the Administration and Coordination Core, AIMDMB Research Projects and Shared Resource Core(s), if any, and their primary functions;
• Indicate the relationship of the Administration and Coordination Core to the administrative structure of the applicant institution and partnering institutions, if any. It should not be presumed that the best way to organize the AIMDMB Center is division along existing institutional boundaries, or the prior research activities of the individual PD(s)/PI(s);
• Describe the strategies that will be implemented to increase representation and career enhancement of underrepresented minorities in the biomedical research workforce who will participate in the Center’s research program;
• Describe strategies to work with the Nutrition for Precision Health consortium and All of Us Research Program, and other NIH AI initiatives to develop transparent, ethical protocols and procedures for working with biomedical data (e.g., data equity, privacy, governance, and bias reduction) as well as strategies to create AI-ready (e.g., well-annotated metadata, requisite sample size and granularity, provenance, multimodal data dynamics and curation needs) biomedical data sets within the All of Us Researcher Workbench;
• Describe the structural and procedural elements governed by the Administration and Coordination Core leadership that will ensure the respective AIMDMB Research Projects, DMAC, and optional Shared Resource Core(s), if any, function to create integration, iteration, and synergy;
• Describe the strategies that will be implemented to phase in and scale up the Center's research program during the first 18-24 months of the program while study data is not available;
• Describe criteria and processes by which AIMDMB Center members are acknowledged in publications resulting from AIMDMB projects and how the Administration and Coordination Core mediates disputes should they arise;
• Describe opportunities for involvement of scientists at all stages of the career pipeline, including students, post-docs, and early stage investigators, both from within and outside of the parent organization. Applicants should also consider what career enhancement opportunities will be provided, such as attending seminars and scientific meetings, writing papers, and giving talks. Long-term sustainability and institutional/governmental commitments to research education and independent career opportunities should be discussed; and
• Describe how the Administration and Coordination Core will manage respective Resource Sharing Plans in accordance with the core values of the All of Us Research Program.

Plans for Pilot Program Structure and Governance:

• Outline a specific mechanism for the selection and approval of the Pilot Projects to be established by the leadership of the proposed AIMDMB Center in consultation with Project and Core Leaders and the Nutrition for Precision Health consortium Steering Committee. Describe the expected participants and duration of the pilot projects, as well as the planned timeline for soliciting, reviewing, and selecting these projects. Potentially, these projects may lead to larger research activities through seeking of separate funding in their later stages;
• Outline strategy for aligning pilot project data sharing with other Nutrition for Precision Health consortium activities and for streamlined data management and analysis plans;
• Describe plans to facilitate these projects within the AIMDMB Center structure; and
• Describe plans for monitoring and evaluating pilot project progress and describe strategy for overseeing funded pilot projects, including the distribution of yearly sub-award funds, especially for those that aren't located at the AIMDMB Center.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Any proposed sharing plan needs to be consistent with the All of Us Research Program’s data sharing policies (https://allofus.nih.gov/about/core-values).
• Resource Sharing Plans should only be included in the Overall component.
• NIH strives to ensure the dissemination of research resources developed with NIH Funds. Detailed Resource Sharing Plans for sharing of intellectual and technological resources is a fundamental aspect of the Nutrition for Precision Health consortium. Resource Sharing Plans should be described here and should be presented as summary of data sharing, management and analysis to be shared. Further, as it is expected that the algorithms, platform technologies, and / or software the Center has developed, will be further validated and improved through the Nutrition for Precision Health consortium's research. Given the high profile of this study, the PD/PI’s tools could become an important resource that other investigators will want to utilize. While the investigators are expected to substantively participate in this research project, the applicants must develop a resource sharing plan inclusive to all Center projects and cores that explains how the developed resource will be made available to the investigator community in the future including the time course for that plan. The sharing plan may include fees for licensing or use of the tools, but may NOT have reach through agreements , for example that require the involvement of particular investigators in research grant applications, percent effort, future co-authorships or other collaboration requirements. The plan should also minimize administrative impediments to academic sharing of research resources.

Appendix:

Only limited items are allowed in the Appendix.Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Project

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: AIMDMB Research Project
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide overall goals/abstract/summary for the AIMDMB Research Project.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Project Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the specific objectives and goals of the AIMDMB Research Project in similar manner as traditional NIH single project applications. The specific aims section should also contain a brief statement about how the project relates with the overall goals of the AIMDMB Center and, as applicable, integration across projects and cores with respect to shared specific aims.

Research Strategy:

This section of the application should address the background and salient approaches and methods in the AIMDMB Research Project with enough detail for critical evaluation of both the quality of the research activities and how they contribute to the AIMDMB Center.

Applicants should highlight the significance of the research project, the expertise of the research team without duplicating information in the biosketches, the innovation of the science, the details of the experimental approach (including a rationale for the methodology), the strengths of the research environment, as well as a description of how the project contributes to the AIMDMB Center. The following subsections are recommended: Significance and Relevance to the Nutrition for Precision Health consortium; Investigators; Innovation; Approach; Environment; and AIMDMB Center Integration. Within the sub-sections, address the following additional aspects of the AIMDMB Research Project:

• Describe the rationale for the proposed technologies and how they relate to development of specific tools in the context-of-use for the Nutrition for Precision Health consortium;
• Describe, as appropriate, complementary technologies or approaches supporting a goal of interoperability, and ability of the project to be responsive to the emerging needs of the Center and the Nutrition for Precision Health consortium;
• The experimental plan that will be employed should be discussed in detail, including methods and technologies. The data to be analyzed should be identified and the research strategy must include data acquisition, storage, etc. (where applicable) relative to the Nutrition for Precision Health consortium and the specific methods by which the applicant plans to work with the All of Us Research Program’s Researcher Workbench. The plan can also include information as to data that will be leveraged to enable more robust methods development, algorithm optimization or other prior to Nutrition for Precision Health study data becoming available (e.g., previously generated or publicly available data that could enable the applicant to maximize impact when study data is available 1-2 years after start date of Nutrition for Precision Health consortium)
• Data science innovation as well as potential needs of the project should be clearly described, including issues of data acquisition, data management, data storage, analytical capability, technology development, intervention validation, etc. The data science and innovation activities may be embedded within the individual research components but should at least be aligned with the DMAC activities. Also, discuss the relevant investigators' multidisciplinary experience without duplicating information in the biosketches.
• The applicant should describe how data will be analyzed, as well as the research team's experience with the relevant data science methodologies. If technology/solution development is proposed, the applicant should describe how it will be assessed and validated, as well as the research team’s experience developing related technology platforms and implementing associated solutions or interventions
• Detail the process to pursue alternative approaches to solving technological problems in development of the methods or technologies, if the main conceptual thrust should prove unfeasible within the AIMDMB Center.

Research project milestones must be included for each project, defining how the applicants propose to achieve major goals of the project. An associated timeline should be included to provide further information regarding the timeframe of each element associated with each project milestone. These milestones and the timeline should be distinct from the overall AIMDMB Center milestones, albeit aligned, and more granular to address how applicants propose to achieve the specific goals of each research project.

Letters of Support: Include letters of support as appropriate.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start). All instructions in the SF424 (R&R) Application Guide must be followed.

When preparing your application, use Component Type Core

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: AIMDMB Data Management and Analysis Core
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide overall goals/abstract/summary for the AIMDMB Data Management and Analysis Core.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the specific objectives and goals of the AIMDMB Data Management and Analysis Core (DMAC). The specific aims section should contain brief statement about how the Core integrates with each of the research projects and cores as well as how it helps to achieve the Center's goals.

Research Strategy: This section of the application should address the resource functions of the AIMDMB Data Management and Analysis Core with enough detail for critical evaluation in the context of the AIMDMB Center.

Applicants should use the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach). Additionally, a comprehensive data management plan that describes the specific objectives and goals of the DMAC to support efficient data management and analysis should include plans for coordination with projects and cores, fostering data sharing and interoperability, as well as data quality assurance and quality control plans. It should also outline methods for measures to mitigate bias in datasets as well as the ethical use of them.

Within these sub-sections, address the following additional aspects of the AIMDMB Data Management and Analysis Core:

• Describe clearly, the relevance of the core to the goals of the overall AIMDMB Center and how this core integrates with other projects and cores. Activities of this core that could assist in solving the problem(s) that the Nutrition for Precision Health consortium is trying to address should also be described;
• Describe how metadata (e.g., data descriptors) and ontologies (or semantic relationships) will be used to harmonize data across the AIMDMB Center and Nutrition for Precision Health consortium to enable interoperability and compatibility as well as to identify the relationships between data. Common protocols where feasible should be used and should capture experimental conditions (i.e., standardized data documentation) and analysis tools (e.g., codes and scripts);
• Describe plans to demonstrate integration of data across AIMDMB Center. These should include discussion of ontology, data structures, standards, data platforms, interfaces, tools, and any data visualization approaches that may be used to facilitate data sharing and integration within the AIMDMB Center;
• Describe plans for DMAC personnel to work with the Center projects and cores to engage in iterative experimentation and/or feedback;
• Describe plans for interfacing with any larger institutional information technology infrastructure(s) and addressing requirements for database structures and security. This should include interfacing with the All of Us Research Program's Researcher Workbench (https://www.researchallofus.org/workbench/);
• Explain the DMAC's process to enabling project and core leaders, trainees as well as to the Nutrition for Precision Health consortium data to analyze shared datasets (for example, exploring new linkages between data and the formation of new hypotheses or other salient aspects of analysis to drive discovery of actionable data-inspired events);
• Describe plans for developing creative approaches that foster the development, or strengthening of existing knowledge about, of artificial intelligence ready data sets (AI-Ready) for biomedical or, more generally, public health utility;
• Plans to establish, coordinate, and monitor processes for data analysis and work closely with project and core leaders to ensure high data quality throughout the entire lifecycle of the data.
• Describe plans to coordinate with project and core leaders to identify opportunities for integrating Nutrition for Precision Health consortium data with other existing datasets, as appropriate.
• Detail the process by which the DMAC will turn over activities to other projects or Nutrition for Precision Health consortium for the iterative cycle of technology development and data inquiry;
• Description of data quality assurance and control procedure(s);
• Describe the overarching process by which AIMDMB Center project and core staff will be trained to implement quality assurance, and who will be responsible for training; and
• Describe plans to demonstrate integration of data across AIMDMB Center. These should include discussion of ontology, data structures, standards, data platforms, interfaces, tools, and any data visualization approaches that may be used to facilitate data sharing and integration within the AIMDMB Center.

Letters of Support: Include letters of support as appropriate. This is recommended for all resources to be leveraged by the DMAC.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

When preparing your application, use Component Type Core

All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions, as noted.

Complete only the following fields:

• Applicant Information
• Type of Applicant (optional)
• Descriptive Title of Applicant’s Project: AIMDMB Shared Resource Core
• Proposed Project Start/Ending Dates

Enter Human Embryonic Stem Cells in each relevant component.

Human Subjects: Answer only the Are Human Subjects Involved? and 'Is the Project Exempt from Federal regulations? questions.

Vertebrate Animals: Answer only the Are Vertebrate Animals Used? question.

Project Summary/Abstract: Provide overall goals/abstract/summary for the RTB.

Project Narrative: Do not complete. Note: ASSIST screens will show an asterisk for this attachment indicating it is required. However, eRA systems only enforce this requirement in the Overall component and applications will not receive an error if omitted in other components.

List all performance sites that apply to the specific component.

Note: The Project Performance Site form allows up to 300 sites, prior to using additional attachment for additional entries.

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.

Budget forms appropriate for the specific component will be included in the application package.

Note: The R&R Budget form included in many of the component types allows for up to 100 Senior/Key Persons in section A and 100 Equipment Items in section C prior to using attachments for additional entries. All other SF424 (R&R) instructions apply.

Specific Aims: Describe the specific objectives and goals of the AIMDMB Shared Resource Core. Further, specific aims section should contain a brief statement about how the Core integrates with the rest of the AIMDMB Center.

Research Strategy: This section of the application should address the resource functions of the optional AIMDMB Shared Resource Core with enough detail for critical evaluation in the context of the AIMDMB Center. Applicants must include the description of the Core, services to be rendered, methodological approaches to be used, and plans for prioritizing the use of the Core by AIMDMB Center members. This section must clearly present the facilities, techniques, and professional skills that the core will provide. Innovation, if not overtly inherent, can be addressed by focusing on the mission critical role that the Core plays for the AIMDMB Center and / or the Nutrition for Precision Health consortium. It should also describe how the AIMDMB Center will be more efficient than if the research projects themselves were to provide the functionality or how the Core provides added value beyond that which would be provided by acquisition through fee for service or commercial access agreements.

Applicants should use the standard structure of the Research Strategy section (i.e., sub-sections Significance, Innovation, and Approach).

Within these sub-sections, address the following additional aspects of the optional AIMDMB Shared Resource Core:

Explain how the Core's focus / function presents an opportunity to demonstrate and optimize AIMDMB Center development or other;

Describe plans for Core's personnel to work with the AIMDMB Center projects and cores and engage in iterative experimentation and feedback;

Explain the Core's process for evaluating success versus potential failures at different stages of the award period and the role of the Core in addressing, as appropriate, such aspects as the availability of new technologies, software, data infrastructures, or other under development;

Detail the process by which the Core will turn over activities, if applicable to its primary function, to the AIMDMB Center or Nutrition for Precision Health consortium in the iterative cycle between technology development and inquiry; and

Describe plans to coordinate with project/core leaders to identify opportunities for integrating Nutrition for Precision Health consortium data with other existing datasets, as appropriate.

Letters of Support: Include letters of support as appropriate. This is recommended for all resources to be leveraged by the Shared Resource Core.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Any proposed sharing plan needs to be consistent with the All of Us Research Program’s data sharing policies (https://allofus.nih.gov/about/core-values).
• Resource Sharing Plans should only be included in the Overall component.

Appendix:

Only limited items are allowed in the Appendix. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide; any instructions provided here are in addition to the SF424 (R&R) Application Guide instructions.

When involving human subjects research, clinical research, and/or NIH-defined clinical trials follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:

If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or a Delayed Onset Study record.

Study Record: PHS Human Subjects and Clinical Trials Information

All instructions in the SF424 (R&R) Application Guide must be followed.

Delayed Onset Study

Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov.

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies) using ASSIST or other electronic submission systems. Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

For information on how your application will be automatically assembled for review and funding consideration after submission go to: http://grants.nih.gov/grants/ElectronicReceipt/files/Electronic_Multi-project_Application_Image_Assembly.pdf.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) and component Project Leads must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management (SAM). Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

Should intramural scientists submit an application through this FOA, or should an extramural application include a collaboration with NIH intramural scientists, the requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.

If selected, appropriate funding will be provided by the Common Fund through the NIH Intramural Program. NIH intramural scientists will participate in this program as PD/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.

Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above and as described in the NIH Intramural Source Book.

Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.

Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission are evaluated for scientific and technical merit through the NIH peer review system.

For this particular announcement, note the following:

A meritorious AIMDMB Center application is expected to be well-balanced in multidisciplinary science that spans expertise in both biomedical data science technology development, computer modeling, and nutrition research (or corollary expertise across those general fields to drive goals of the AIMDMB Center with impact to the needs of Nutrition for Precision Health consortium). The overarching goal for Nutrition for Precision Health is to overcome past nutrition barriers in health outcomes. This will be implemented by way of a consortium with national impact that is at the forefront of developing the data, processes, and technology to acquire signatures of human health with respect to nutrition. Meritorious applications are anticipated to articulate how the iteration between the AIMDMB Center (and its projects and cores) as well as the broader Nutrition for Precision Health consortium will produce uniquely enabling resources that advance our fundamental understanding of human health with respect to nutrition.

The common study protocol for Nutrition for Precision Health will be developed during the first year of the award and implemented by all Centers beginning in year 2.

The first year will serve as a planning year.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the AIMDMB Center as a whole to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the Center proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a AIMDMB Center that by its nature is not innovative may be essential to advance a field.

Does the AIMDMB Center address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the AIMDMB Center are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: Are the platform technologies, software and computational approaches proposed for development by the AIMDMB Center likely to become an important resource for the Nutrition for Precision Health consortium researchers? In a broad sense, will the work proposed further our understanding of the field of precision nutrition? What is the potential for wider adoption of technical or conceptual innovation developed by the AIMDMB Center in the long-term by the broader biomedical and data science research fields?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the AIMDMB Center? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Specific to this FOA: How well does the proposed AIMDMB Center utilize combined expertise in artificial intelligence / computer modeling, bioinformatics platform development and nutrition research? Are the applicant PD(s)/PI(s) recognized as leaders in their respective fields with experience in managing multidisciplinary teams? Are collaborators likely to work together synergistically and enhance the potential impact of the research and activities proposed? Are the applicant PD(s)/PI(s) dedicating sufficient level(s) of effort to the AIMDMB Center?

Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed?

Specific to this FOA: Do the proposed data science-driven approaches lead toward novel solutions for nutritional health barriers or advance understanding of nutrition with respect to Precision Health? Does the application uniquely combine platform technologies, biomedical data science, and nutrition or -omics research in a manner that is 1) enabling for the Nutrition for Precision Health consortium and development of multimodal signatures of health with respect to nutrition, 2)toward novel solutions for nutritional health barriers or advance understanding of nutrition with respect to Precision Health and subsequent disease, and 3) for the broader biomedical research and data science communities?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the AIMDMB Center? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Specific to this FOA: How well does the application justify the rationale and motivation for selection of the theoretical concepts, technologies, approaches or methodologies, data sets and infrastructure, to address the research challenge(s) that defines the Nutrition for Precision Health consortium? Does the approach have the requisite synergy and structure of projects and cores to have overall additive value versus simply a collection of individual projects to achieve impact, in terms of the Nutrition for Precision Health consortium? Does the approach enable an iterative methodology to amplify new research findings or discoveries from the Center, Nutrition for Precision Health consortium, or external research community further, faster?

Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Specific to this FOA: Does the applicant institution(s) have existing technology development infrastructure, resources, or cores that can be leveraged to complement the proposed AIMDMB Center? Willexisting or proposed external partnerships through foundations or industry extend the resources for the AIMDMB Center? How well does the environment facilitate multidisciplinary relationships and the iterative flow between the AIMDMB Research Projects as well as between DMAC Core and AIMDMB Shared Resource Core(s), if any?

As applicable for the AIMDMB Center proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

Integration

Will the proposed AIMDMB Center be a truly integrated entity, rather than a collection of unrelated research projects and support services? Does the proposed AIMDMB Center address the need and the methodology to deliver a suite of computational tools to perform data integration, harmonization, analysis and visualization of the multi-modal and multi-fidelity data as well as incorporate an adaptive design for future data incorporation? Does the proposed AIMDMB Center address the need and the methodology to deliver comprehensive dietary intervention algorithms that can predict biological responses, available energy, and individual health trajectories from multiple types of input data by way of Nutrition for Precision Health study and / or other available data sets? Does the proposed AIMDMB Center address the need and the methodology to deliver adaptive, predictive algorithms and visualization software / tools for interrogation of Nutrition for Precision Health study, retrospective, or future prospective data for the broader biomedical research community? How well does the AIMDMB Center organization promote scientific, technical, and administrative integration, synergy and a cohesive research program? Does the application include overall Center performance-based milestones addressing how the key goals of the AIMDMB Center will be achieved as well as timeline for interactions of project and core milestones across the center? Does the applicant adequately describe plans to collaborate and share models, software, and other resources within the AIMDMB Center and across the Nutrition for Precision Health consortium? Do the proposed components require a Center-based research structure for success?

Consortium Activities

Have the investigators stated their willingness to collaborate with NIH scientists and staff, and with investigators and staff from other components of the Nutrition for Precision Health consortium, including the All of Us Research Program? Have the investigators stated a willingness to participate in planning the study and to use common protocols? Have the investigators agreed to uphold to the All of Us Research Program Core Values (https://allofus.nih.gov/about/core-values) and Privacy and Trust Principles (https://allofus.nih.gov/protecting-data-and-privacy/precision-medicine-initiative-privacy-and-trust-principles)?

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. The AIMDMB Research Project does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a AIMDMB Research Project that by its nature is not innovative may be essential to advance a field.

Impact Score

• Reviewers will provide an impact score to reflect their assessment of the likelihood for the research project to exert a sustained, powerful influence on the research field, in consideration of the following review criteria.

Significance

• Does the AIMDMB Research Project provide the rationale for the proposed technologies and how they relate to development of a specific tools in the context-of-use for the Nutrition for Precision Health consortium? How will successful completion of the aims change the concepts, methods, technologies, or services drive the field of biomedical data science of public health? Is the prior research that serves as the key support for the proposed AIMDMB Research Project rigorous? How well does the AIMDMB Research Project advance the overall research or collective output of the AIMDMB Center?

Investigator(s)

• Are the Project Lead(s), collaborators, and other researchers well suited to the AIMDMB Research Project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If the AIMDMB Research Project is collaborative or has multi-Unit Leads, do the investigators have complementary and integrated expertise? Does the AIMDMB Research Project optimally use the combined multidisciplinary research expertise? How does the AIMDMB Research Project benefit from the unique scientific expertise of the AIMDMB Center?

Innovation

• Does the application challenge and seek to shift current research or clinical practice paradigms by utilizing novel theoretical concepts, approaches or methodologies, instrumentation, or interventions? Does the project offer innovation by way of novel use of existing methods, technologies or tools, by formation of novel ones, or by both (any is appropriate as long as they drive the collective goals of the AIMDMB Center)? Are the concepts, approaches or methodologies, instrumentation, or interventions novel to one narrow field of research or novel in a broad sense? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, instrumentation, or interventions proposed? Does the project propose an innovative solution to a critical barrier to progress in the understanding of how biomedical data science and innovation can be leveraged to address critical health priorities for Nutrition for Precision Health? Is a refinement, improvement, or new application of theoretical concepts, approaches or methodologies, models, or interventions proposed?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the AIMDMB Research Project? Have investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the AIMDMB Research Project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility, and will particularly risky aspects be managed? Is a process to pursue alternative approaches to solving technological problems in development of the methods or technologies, if the main conceptual thrust should prove unfeasible within the AIMDMB Center reasonable? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the Center involves human subjects and/or NIH-defined clinical research, are the plans to address:

1) the protection of human subjects from research risks, and

2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?

Environment

• Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? Will the AIMDMB Research Project benefit from unique features of the scientific environment of the AIMDMB Center, Nutrition for Precision Health study population data, or other proposed collaborative arrangements?

• Reviewers will provide only one score/adjectival rating for the Administration and Coordination Core (criterion scoring is not used for this component). Reviewers will consider the following criteria to determine an impact score:
• Are the approaches, methods, and expertise proposed for the AIMDMB Data Management and Analysis Core adequate to achieve objectives to support the AIMDMB Center?
• Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the AIMDMB Data Management and Analysis Core?
• Are the objectives of the Data Management and Analysis Core appropriate to meet the needs of the Center? To the Nutrition for Precision Health consortium?
• Are plans for interfacing with any larger institutional information technology infrastructure(s) and addressing requirements for database structures and security appropriate? This should include interfacing with the All of Us Research Program's Researcher Workbench.
• Is the plan for leveraging the advances made by AIMDMB Center reasonable and achievable?
• Are the plans to support the data analytic, integration, and sharing efforts of projects and cores reasonable and adequate? Do these plans enable enhanced synergy and integration across the AIMDMB Center?
• Are strategies for developing creative approaches that foster the development, or strengthening of existing knowledge about, of artificial intelligence ready data sets (AI-Ready) for biomedical or, more generally, public health utility reasonable?
• Are the plans to demonstrate integration of data across AIMDMB Center reasonable? These should include discussion of ontology, data structures, standards, data platforms, interfaces, tools, and any data visualization approaches that may be used to facilitate data sharing and integration within the AIMDMB Center
• Are strategies to work with the Nutrition for Precision Health consortium, All of Us Research Program, and other NIH AI initiatives reasonable? Do they offer a well thought approach to amplify or benefit the broader biomedical data ecosystem or the application of AI for biomedical research?
• Is a process by which the Data Management and Analysis Core will turn over activities to other projects or Nutrition for Precision Health consortium for the iterative cycle of technology development and data inquiry as well as data quality assurance and control procedure(s) reasonable?
• Are the methods outlined for measures to mitigate bias in datasets as well as the ethical use of them appropriate?

• Reviewers will provide only one score/adjectival rating for the Administration and Coordination Core (criterion scoring is not used for this component). Reviewers will consider the following criteria to determine an impact score:
• Are the approaches, methods, and expertise proposed for the Shared Resource Core adequate to achieve objectives to support the AIMDMB Center?
• Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Shared Resource Core?
• Are the objectives of the Shared Resource Core appropriate to the AIMDMB Center appropriate to meet the needs of the Center and to the Nutrition for Precision Health consortium?
• Is the plan for leveraging the advances made by Shared Resource Core reasonable and achievable?
• Are the plans to support the efforts of projects (and cores) reasonable and adequate? Do these plans enable enhanced synergy and integration across the AIMDMB Center?
• Is the Shared Resource Core's process for evaluating success versus potential failures at different stages of the award period and the role of the Core in addressing, as appropriate, such aspects as the availability of new technologies, software, data infrastructures, or other under development adequate?
• Are strategies to work with the Nutrition for Precision Health consortium, All of Us Research Program, and other NIH AI initiatives reasonable? Do they offer a well thought approach to amplify or benefit the broader biomedical data ecosystem or the application of AI for biomedical research?
• Is a process by which the Shared Resource Core will turn over activities to other projects or Nutrition for Precision Health consortium for the iterative cycle of technology development and data inquiry as well as data quality assurance and control procedure(s) reasonable?

For research that involves human subjects but does not involve one of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed unit involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of individuals of all ages (including children and older adults) to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the AIMDMB Center proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan .

For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

Reviewers will consider whether the budget and the requested period of support are fully justified and reasonable in relation to the proposed research.

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by NIH Center for Scientific Review, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.

After the peer review of the application is completed, the PD/PI will be able to access his or her Summary Statement (written critique) via the eRA Commons. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the recipient’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.

All NIH grant and cooperative agreement awards include the NIH Grants Policy Statement as part of the NoA. For these terms of award, see the NIH Grants Policy Statement Part II: Terms and Conditions of NIH Grant Awards, Subpart A: General and Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.

HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.

• Recipients of FFA must ensure that their programs are accessible to persons with limited English proficiency. HHS provides guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see https://www.hhs.gov/civil-rights/for-individuals/special-topics/limited-english-proficiency/fact-sheet-guidance/index.html and https://www.lep.gov. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at https://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.
• Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html.
• HHS funded health and education programs must be administered in an environment free of sexual harassment. Please see https://www.hhs.gov/civil-rights/for-individuals/sex-discrimination/index.html; https://www2.ed.gov/about/offices/list/ocr/docs/shguide.html; and https://www.eeoc.gov/eeoc/publications/upload/fs-sex.pdf. For information about NIH's commitment to supporting a safe and respectful work environment, who to contact with questions or concerns, and what NIH's expectations are for institutions and the individuals supported on NIH-funded awards, please see https://grants.nih.gov/grants/policy/harassment.htm.
• Recipients of FFA must also administer their programs in compliance with applicable federal religious nondiscrimination laws and applicable federal conscience protection and associated anti-discrimination laws. Collectively, these laws prohibit exclusion, adverse treatment, coercion, or other discrimination against persons or entities on the basis of their consciences, religious beliefs, or moral convictions. Please see https://www.hhs.gov/conscience/conscience-protections/index.html and https://www.hhs.gov/conscience/religious-freedom/index.html.

Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) 2 CFR Part 200 Administrative Regulations, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, NIH Grants Policy Statement (which implements the aforementioned HHS Regulations (45 CFR Part 75), and other HHS, PHS, and NIH grant administration policies.

The administrative and funding instrument used for this program will be the cooperative agreement, an "assistance" mechanism (rather than an "acquisition" mechanism), in which substantial NIH programmatic involvement with the awardees is anticipated during the performance of the activities. Under the cooperative agreement, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients in a partnership role; it is not to assume direction, prime responsibility, or a dominant role in the activities. Consistent with this concept, the dominant role and prime responsibility resides with the awardees for the project as a whole, although specific tasks and activities may be shared among the awardees and the NIH as defined below.

1. Primary responsibilities of the PD(s)/PI(s)

The PD(s)/PI(s) will have the primary responsibility for:

• All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, setting project milestones, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms.
• Awardee(s) will provide goals and progress toward those goals at regular intervals as requested by NIH staff and ensure that the data produced meets the quality standards agreed to by the consortium.
• Awardee(s) will ensure that data are submitted in a timely fashion to the All of Us Researcher Workbench, that resources developed as part of this project are made publicly available according to consortium policies, and that results are disseminated in a timely manner. The PD/PI is responsible for the proper stewardship of the data, including accurate annotation, disclosure of any pre-processing, data use limitations, data provenance and other associated metadata as determined by any consortium and All of Us policies.
• Ensuring that software and other tools and resources developed as part of this project are made publicly available according to Nutrition for Precision Health and All of Us policies, and that research products of the project are published in a timely manner. The PD/PI is expected to fully disclose data, algorithms, software source code, and experimental methods to the other members of the consortium or the External Program Consultants for the purpose of scientific evaluation and use by other consortium members in collaborative projects.
• Awardee(s) will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."
• Agreeing to the governance of the consortium through the SC and the NIH WG, including accepting approved recommendations from the EPCs.
• Actively participating in the SC, including attending both in-person and teleconference meetings, and participating in collaborative activities and subcommittees and ensuring timely completion of key SC tasks, such as finalization of the protocol, finalization of data sharing or other policies. At least one in-person SC meeting will be held per year, for which Nutrition for Precision Health awardees will pay the travel for their attending members. The PD/PI is expected to attend at least one consortium meeting in person each year.
• Updating goals and milestones at the time of award and providing summaries of progress toward those goals at least yearly, as requested by NIH. The milestones will be reviewed annually (and at other times, if necessary), and new milestones will be negotiated, as needed by working with the NIH WG and Project Scientists as appropriate.
• Agreeing to abide by any policies and maintaining documentation of compliance -- including those regarding intellectual property, data and software sharing, publication of Nutrition for Precision Health consortium papers, reagent and protocol sharing, standards and calibration, metadata requirements, data use limitations and public copyright licensing -- that are recommended by the SC and approved by the NIH WG, as well as applicable NIH policies, laws, and regulations.
• Being prepared for annual administrative site visits or virtual site visits by NIH staff.
• Agreeing to participate in the collaborative activities of the consortium and agreeing not to disclose confidential information obtained from other members of the consortium including, without limitation, unpublished data, informatics tools, protocols, data analysis, confidential exchanges between members of the consortium, as well as any confidential information received by third party collaborators.
• Awardees will retain custody of and have primary rights to software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

2. NIH Staff Involvement

Definitions

• NIH Working Group (NIH WG): Consists of NIH programmatic staff from multiple Institutes and Centers of the NIH as well as the Office of the Director. This group will be primarily responsible for the stewardship of the Nutrition for Precision Health Program and will participate as non-voting members in the Consortium committees. The Nutrition for Precision Health WG is co-chaired by the Directors of the All of Us Research Program, NIDDK, NHLBI, NCI, and NICHD. It reports to the Directors of the Office of Strategic Coordination/Common Fund and the Division of Program Coordination, Planning, and Strategic Initiatives for final funding decisions.
• Nutrition for Precision Health Coordinators: Two Coordinators are NIH extramural scientists who serve as Program Managers and are responsible for the overall and day-to-day management of the Consortium, progress towards the program’s goals and monitoring interactions between the Consortium and the external community. They will have substantial involvement in assessing progress and making recommendations about future funding. The Nutrition for Precision Health Coordinators will have substantial scientific programmatic involvement in the direction of all the Nutrition for Precision Health awards and may consult other NIH and non-NIH experts in making determinations. They will participate as members of all Consortium committees and will review and approve Consortium policies. The Nutrition for Precision Health Coordinators will not co-author publications with project investigators.
• Steering Committee (SC): The purpose of the SC is to recommend direction for the Nutrition for Precision Health consortium consistent with the program goals, develop consortium policies and projects to build synergy and improve communication and collaboration between the projects, and to provide a forum for discussing progress, challenges and opportunities for the consortium. The SC will include PDs/PIs of each of the awards and NIH WG members. The SC will be chaired by two PD/PIs that are approved by the NIH WG. An Executive Committee (EC) composed of the co-chairs and the NIH Program Officers and Coordinators will meet to set the agenda for SC meetings. The SC will establish subcommittees to oversee the development and implementation of consortium policies including data release, publications and standards. It is expected that most of the decisions on the activities of the Nutrition for Precision Health Steering Committee will be reached by consensus. If a vote is needed, each project PD/PI (or Contact PI in the case of multi-PI projects) will have one vote. NIH staff will be non-voting members of the SC but will review and approve policies developed by the Steering Committee. When a vote is required, at least 60% of the votes will be required for approval. Steering Committee recommendations will go to the Nutrition for Precision Health Coordinators and the NIH Working Group for approval.
• External Program Consultants (EPCs): As part of the Nutrition for Precision Health program, NIH staff will engage 4-6 External Program Consultants (EPCs) not funded as part of the program but with relevant scientific and consortium experience to provide input and advice to the NIH WG. This could include reviewing and evaluating the progress of the entire Nutrition for Precision Health Program or individual awardees as well as recommending changes in priorities for the Nutrition for Precision Health Program based on scientific advances within and outside of the consortium. The EPCs will be senior, scientific experts who are not directly involved in the activities of the Nutrition for Precision Health Program and who agree to a confidentiality policy, engaged on an as-needed basis to advise on specific issues. NIH is solely responsible for appointing EPCs for variable durations of service. EPCs are invited to participate in consortium meetings and Steering Committees calls and the annual investigators meeting. A subset of EPCs may also meet by phone or web at other times of the year, as needed. Annually, the EPCs will provide individual assessments to the NIH of the progress of the consortium and will present individual expert recommendations regarding any changes in the Nutrition for Precision Health Program as necessary. The assessments and recommendations will be provided through the NIH WG to the Director of the Office of Strategic Coordination, NIH
• Nutrition for Precision Health Consortium: The Nutrition for Precision Health consortium is made up of Nutrition for Precision Health awardees, the NIH WG and other scientists and groups the SC agrees to include within the consortium. The consortium structure is meant to efficiently and effectively guide all the funded projects to meet the overall goals of the Nutrition for Precision Health Program.

For each individual award, NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• NIH Project Scientist(s) - One or more NIH Program Staff will serve as Project Scientists (PSs), for each Nutrition for Precision Health award and, as appropriate, to oversee collaborative projects amongst awardees and/or other consortium members. The PSs will serve as the scientific representatives of the NIH to the investigators in accordance with policies and procedures of the cooperative agreement mechanism. If there is more than one PS, one of them will be designated as the Lead PS. PSs will work closely with the PD/PI, the Steering Committee, and the PIs of all projects/cores to maximize progress towards the goals of the project and the program by providing advice and guidance to ensure that the project adheres to the objectives of the FOA, the Terms and Conditions of the award, and other agreements between the awardees and NIH. The Project Scientist may provide scientific and programmatic assistance to the PD/PI, including contributing to data analysis, key personnel selection, and promoting the availability of data and resources. The Project Scientist(s) will attend all official business meetings of the project's leadership The Project Scientist(s) will not make decisions about the funding of this project and will not be involved in any special reviews of the project that make recommendations about funding.
• The Nutrition for Precision Health Coordinators will work closely with the Program Officer and Project Scientist(s) to monitor progress of the project and coordinate collaborative projects, resource sharing and outreach as part of the consortium. The Coordinators will keep the PD(s)/PI(s) informed of consortium-wide activities, policies and issues. The Nutrition for Precision Health Coordinators will not co-author publications with project investigators

The NIH will designate program staff, including a Program Officer and a Grants Management Specialist to provide stewardship and administrative oversight of the cooperative agreement. The Program Officer and Grants Management Specialist will be named in the Notice of Grant Award.

• NIH Program Officer - A NIH Program Officer (PO) is responsible for the normal scientific and programmatic stewardship, including monitoring progress and compliance with general statutory, regulatory, or policy requirements; NIH also reserves the right to modify the budget or duration of funding or to curtail an award in the event of: (a) substantive changes in the project not approved in advance, (b) use of funds for activities not within the scope of the specific aims, (c) failure to make sufficient progress toward the project milestones, including timely pre-publication deposition of data or reagents in accordance with approved consortium Policies, (d) failing to comply with the terms and conditions of the award or establish necessary statutory, regulatory, policy approval required for conducting the project, or (e) ethical or conflict of interest issues.
• NIH staff and their respective Institutes and Centers will manage Conflicts of Interest and Management of Bias as detailed in the NIH Policy Manual. The Program Officer will not co-author publications with project investigators.
• Progress Reviews. The annual evaluation by the Program Officer and Coordinators will be based on the non-competing application and progress report, , and assessments by the Project Scientist(s). In addition, NIH staff may conduct interim reviews of scientific progress beyond the normal yearly non-competing progress review to determine progress and use information from progress reviews to inform future funding for the project.
• Special Reviews. In addition, if concerns are identified about the performance or the management of the project, the Program Officer may conduct special reviews of the project as he/she deems necessary. NIH may engage outside experts to assist in these reviews. If concerns about the project arise and are not resolved, NIH may reduce or restrict the budget or reduce the term of support to phase out the project.
• Funds may be restricted pending completion of key tasks, such as finalization of the protocol, finalization of data sharing or other policies, or transfer of data to the Research Coordinating Center and/or All of Us Researcher Workbench.

3. Areas of Joint Responsibility

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH during each phase of the program. The awardees, the PSs, and other designated NIH Staff will participate in the annual in-person investigator meeting and scheduled conference calls and share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings. EPCs will attend the annual in person meetings. Other government staff may also attend the annual investigators meetings.

The SC will serve as the main scientific body of the consortium, with the following roles:

• The SC will be responsible for coordinating the activities of the projects and is the committee through which the NIH WG formally interacts with the investigators. SC membership will include the PI(s) of each Project (limited to one vote for a Project with multiple PIs) and NIH staff (non-voting members). The SC Chair(s) will be appointed by the Nutrition for Precision Health Coordinators and drawn from the individual project PIs. The SC may add additional, non-voting, members, as needed.
• All major scientific and policy decisions will be determined by voting policies as established by the Charter for the Steering Committee. Specific activities of the SC will include, but are not limited to: developing and reviewing consortium policies; identifying impediments to program goals and strategies to overcome them; approving and reviewing development of shared tools and collaborative projects; identifying opportunities for sharing techniques, materials, information and tools developed within each individual Nutrition for Precision Health project; facilitating communication and fostering collaboration across the consortium; reviewing progress of the consortium towards meeting the overall consortium goals; developing, adopting or updating data standards, metadata requirements, data quality standards, and submission and release policies; ensuring the consortium leverages existing resources and programs to accelerate progress; helping organize the scientific agenda for the annual Investigator Meeting.
• The SC may choose to open consortium membership to collaborators not funded through the Nutrition for Precision Health Program, provided that such members agree to abide by policies enacted by the SC. The SC may generate additional conditions that apply to non-awardee members of the consortium.

The SC may set up subcommittees as needed to address particular issues. These subcommittees will include representatives from the Nutrition for Precision Health projects, NIH staff and possibly other experts. The SC will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees. The SC is responsible for recording and archiving decisions made, and for assessing the advice of subcommittees in a methodical manner. It is anticipated that multiple subcommittees may need to be formed to address important topics, including but not limited to policies, communications and engagement, recruitment and retention, publications and presentations, and data quality and completeness.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and post-submission issues)

Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
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Christopher M Hartshorn, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3315
Email: [email protected]

Jacinta Bronte-Tinkew, Ph.D.
Center for Scientific Review (CSR)
301-806-0009
[email protected]

Dawn Mitchum
National Cancer Institute (NCI)
Telephone: 240-276-5699
Email: [email protected]

Recently issued trans-NIH policy notices may affect your application submission. A full list of policy notices published by NIH is provided in the NIH Guide for Grants and Contracts. All awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75.