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 toall 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. Applicationsthat do not comply with these instructions may be delayed or not accepted for review,

Part 2. Full Text of Announcement

Section I. Funding Opportunity Description

Human BioMolecular Atlas Program (HuBMAP)

The vision for the Human BioMolecular Atlas Program (HuBMAP) is to catalyze development of a framework for mapping of the human body at high resolution to transform our understanding of tissue organization and function. This will be achieved by:

• Accelerating the development of the next generation of tools and techniques for constructing high resolution spatial tissue maps that quantify multiple types of biomolecules either sequentially or simultaneously;
• Generating foundational 3D tissue maps using validated high-content, high-throughput imaging and omics assays;
• Establishing an open data platform that will develop novel approaches to integrating, visualizing and modelling imaging and omics data to build multi-dimensional maps, and making data rapidly findable, accessible, interoperable, and reusable by the global research community;
• Coordinating and collaborating with other funding agencies, programs, and the biomedical research community to build the framework and tools for mapping the human body;
• Supporting pilot projects that demonstrate the value of the resources developed by the program to study individual variation and tissue changes across the lifespan and the health-disease continuum.

This program is funded through the NIH Common Fund as a short-term, goal-driven strategic investment, with deliverables intended to catalyze research across multiple biomedical research disciplines. The NIH Common Fund 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.

The HuBMAP Consortium will scale-up the range of tissues, technologies, data management and its community engagement activities throughout the duration of the program.

The five research initiatives that compose the program are:

• Transformative Technology Development?- This set of initiatives, issued in FY2018 and FY2020, has focused on establishing proof-of-principle with initial validation of transformative new tools, techniques and methods for mapping the human body at high resolution.
• Rapid Technology Integration?- This initiative, issued in FY2019, has focused on improving the quality and throughput of map generation at key steps of the production pipeline including sample collection, tissue mapping, and data integration and analysis.
• Tissue Mapping Centers? This set of initiatives, issued in FY2018, FY2020 and FY2022, seeks to build, benchmark, standardize, validate, and generate extensive data from high-content, high-throughput imaging and omics technologies to produce 3D human tissue maps at high resolution. Centers are expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through to data integration, analysis and interpretation.
• The HuBMAP Integration, Visualization and Integration (HIVE) Collaboratory?- This set of initiatives issued in FY2018 and FY2022 support a multi-component collaboratory that is responsible for: 1) managing the data generated by the Consortium, 2) coordinating internal and external Consortium activities, 3) developing novel tools for visualizing, searching and modelling data and 4) building an atlas of tissue maps.
• Demonstration Projects?- The goal of this initiative, issued in FY2022, is to demonstrate how HuBMAP resources, in combination with new or other datasets or biospecimens as needed, can be used to build better statistical and analytic tools and models of cellular organization and communication in tissues.

Background

Understanding how tissue organization influences a cell’s molecular state, interactions, and history is critical for enhancing our understanding of variation in organ function across the lifespan and health-disease continuum. Despite vastly improved imaging and omics technologies as well as many important foundational discoveries, our understanding of how tissues are organized is restricted to a very limited number of microscopic structures. Better insights into the principles governing organization-function relationship will potentially lead to better understanding of the significance of inter-individual variability, changes across the lifespan, tissue engineering, and the emergence of disease at the biomolecular level. However, integrating imaging and omics analysis to comprehensively profile biomolecular distribution and morphology of tissues in a high throughput manner and placing this information into 3D tissue maps amenable to modelling has yet to be fully realized.

In a?June 2016 meeting organized by the NIH, experts from the research community identified the following scientific priorities necessary to develop these tissue maps: 1) sourcing high quality tissue from multiple human normal organ sites, 2) processing and preserving tissue for multiple imaging and omics assays, 3) quality control, validation and variation in data generation, 4) data coordination across multiple acquisition techniques, 5) annotation, curation and archiving of the data, 6) browsing, visualizing and searching the data, 7) building statistical and analytic techniques and models for nonlinear analysis of highly multidimensional data and 8) community engagement.

The HuBMAP program was designed to tackle these priorities in four stages: a setup phase in 2018, a scale-up phase from 2019 to 2021, a production phase from 2022 to 2025 including a transition phase in 2025.The Consortium has made significant progress during the setup and scale-up phases and further information can be found on the Consortium’s website. This funding opportunity is designed to support the production phase of the program.

Objectives and Scope for the Tissue Mapping Centers

This FOA seeks to support state-of-the-art Tissue Mapping Centers (TMCs) that will serve as the core data generators for the HuBMAP Consortium by generating a high-resolution, multi-parameter, 3D atlas of a non-diseased human organ. Successful centers will build, benchmark, and standardize pipelines for generating, validating, and analyzing data from multiplexed, high-throughput imaging and omics technologies. Centers will be expected to integrate and optimize all parts of the data generation pipeline, from tissue collection and preservation through to data integration, analysis and interpretation in order to build high-resolution maps. Centers will use these maps to provide new insights into intra-, inter-, and extra- cellular organizational features that influence tissue function, vary across individuals or that change across the lifespan. By the end of four years of funding, a successful center will have created a significant number of high-resolution, multi-scale, multi-dimensional molecular, cellular, and morphological maps from multiple donors that are integrated into a published reference atlas for that organ.

Centers funded by the FOA will be expected to work closely with the existing HuBMAP Consortium and to harmonize their workflows nimbly and rapidly with existing Consortium processes. Centers are required to include a core set of assays: multiplexed immunoassay, single cell RNA sequencing, and at least one other high spatial resolution technology. Centers are also expected to build on the work of the Consortium to complete the atlas of an organ already being studied by the Consortium. Programmatic priority will be given to projects that already have access to high quality tissue from a diverse range of donors (including sex, age, race, and ethnicity), a strong track record of generating high resolution data, and have a compelling and realistic vision for how their selected organ atlas will be completed in 4 years. For further information about the current HuBMAP Consortium, please see:?https://commonfund.nih.gov/hubmap.

Research Focus

The success of HuBMAP is dependent on building a community resource that can be utilized easily and effectively by the wider research community. All TMCs are expected to generate resources, such as high-quality data, metadata, software or protocols, and to make these rapidly and openly available for use by the Consortium and research community. Making data, metadata, software and other digital objects open, findable, accessible, interoperable, and reusable (FAIR) and citable and for those datasets to be rigorous and reproducible are critical to the success of the program. In order for TMCs to get up and running quickly, applicants are strongly encouraged to optimize or adapt appropriate existing tissue collection protocols, assays, and analytical methods and to create new ones only when required. Applicants are also strongly encouraged to optimize or adapt solutions from other communities that have tackled similar mapping challenges. New Centers can propose partnering with existing Consortium members, be composed of, or to partner with funded groups in the wider international atlas-building ecosystem. However, if they do so, they should provide a compelling explanation of why no overlap exists.

NIH expects and will prioritize supporting Centers that will complete building an atlas for the following organs: kidney, colon, spleen, thymus, lungs, bladder, skin, heart, female reproductive organs, eyes, bone and bone marrow, pancreas, and liver. In addition, the NIH expects to support at least one Center focused on mapping the vasculature, lymphatic, and peripheral nervous system in multiple organs. Accordingly, applicants should be cognizant that TMCs will be expected to work closely together.

This FOA encourages applicants to propose strategies that include but are not limited to addressing the following challenges:

• Capturing and preserving tissue location and orientation during collection using the Common Coordinate Framework developed by the HuBMAP Consortium;
• Characterizing and minimizing degradation of tissue during collection and pre-analytical processing;
• Optimizing pre-analytical processing of tissue for multiple imaging and omics assays;
• Establishing calibration standards and technical variability of assays;
• Collecting biospecimens and experimental metadata in a consistent and interoperable format using existing, established ontologies and standards where appropriate.
• Integrating, automation, benchmarking and validation of imaging and omics assays;
• Combining multiple assay types;
• Characterizing and reducing technical variation of common assays;
• Identifying and analyzing missing, incorrect or sparse data;
• Integrating, segmenting and annotating imaging and omics data at multiple spatial scales to build multiplexed, multiscale tissue maps;
• Building a multiscale view for comparison of multiple whole organs;
• Identifying and analyzing neighborhoods and microenvironments in tissues including intra- and extra-cellular environments;
• Annotating, analyzing, and interpreting multi-cellular and non-cellular neighborhoods based upon identification of cell type, state, and spatial interactions between cells and/or components within the extracellular microenvironment;
• Using molecular characteristics to infer time-dependent and space-dependent phenotypes and functional states, such as diversity of quiescence and senescence states, correlation in cell-cell signaling, long-distance signaling and chronobiology;
• Collecting and analyzing tissue to understand the degree of organizational variability in the same tissue from different individuals or multiple tissues from the same individual;
• Understanding how changes in tissue organization impact function across the lifespan and the health-disease continuum.

Applications addressing the following topics will be deemed non-responsive and will not be reviewed:

• Projects primarily focused on the pursuit of a biological mechanism through basic research that does not result in the generation of comprehensive tissue maps;
• Projects proposing maps constructed through use of non-human or biospecimens with diseased or dysfunctional characteristics;
• Projects proposing maps based upon a single experimental assay (i.e. maps constructed from a single data type);
• Projects that do not propose a core set of assays, including multiplexed immunoassay, single cell RNA sequencing, and at least one other high resolution spatial technology;
• Projects proposing to primarily study fluids or dissociated cells; or
• Projects that do not propose all the required components of the TMC organization or fail to include a detailed Resource Sharing Plan or Plan for Enhancing Diverse Perspectives as described below.

Biological Samples

Centers should have a clear vision and detailed plan for mapping non-diseased human organs and tissues from a diverse set of donors during the funding period. Centers are strongly encouraged to develop enrollment criteria and acquisition strategies that will minimize the risk of abnormal or degraded tissue as part of a quality management strategy. Applicants must describe plans for biospecimen management, quality control, minimization of tissue degradation, and ensure their institutional policies and informed consent are consistent with the Consortium's Data Use and Material Transfer Agreements (see:?https://hubmapconsortium.org/policies/). Applicants are also strongly encouraged to pursue explicit consent from the donor or their family for unrestricted sharing of data for research purposes to maximize the utility of biospecimens and data and to have clear plans for maximizing the diversity of their donors.

Teams are encouraged to have strong scientific justification for their choice of number and locations of tissue samples to be analyzed and to consider availability of high-quality tissue, synergies with other initiatives, and matching technical expertise of specific tissues with general technology capabilities. Centers are strongly encouraged to identify robust biological and statistical rationales for sampling decisions and to consider an adaptive experimental design for data collection driven by the needs of their final reference model of the organ. Applicants are also encouraged to consider Ethical, Legal and Social Issues (ELSI) of tissue collection and to consider return of results to donors or their families. Programmatic priority will be given to Centers with established repositories of tissue collected through informed consent from a diverse range of donors or their families for explicit sharing of genomic data and that commit to depositing tissues samples in an accessible biorepository by the end of the funding period.

Centers should?anticipate working closely with the rest of the consortium around biospecimens. TMCs are expected to collaborate closely with each other by sharing biospecimens, protocols (e.g. posting them on the HuBMAP protocols.io workspace) and data, for example as part of the consortium-wide collaborative project. In addition, they should anticipate working closely with the HIVE on the coordination and tracking of biospecimens using the Consortium’s UUID system along with standardizing clinical and collection metadata, collecting tissues consistent with the needs of the Common Coordinate Framework and on the formats and annotations required for successful data submission to the archive. TMCs are also expected to collaborate closely with the TTD and demonstration projects to provide a testbed for validating emerging technologies and generate relevant datasets.

Experimental Assays?

HuBMAP projects will generate high resolution, high content, high-throughput biomolecular data to generate 3D tissue maps of non-diseased human organs and organ systems. For HuBMAP,?a high-resolution assay?is one that can reliably and reproducibly assign detected biomolecules to individual cells or extracellular compartments within a tissue. A high content approach is one that maximizes identification of tissue features through a combination of biomolecular depth, spatial resolution and multiplexing of complementary, multi-parameter assays. A high throughput pipeline is one that maximizes the bandwidth of data production to result in any or all of the following: 1) accelerated speed of analysis, so that hundreds or thousands of samples can be analyzed simultaneously, 2) greater depth of analysis, so that hundreds or thousands of molecules can be analyzed in a single sample, or 3) enhanced capacity for volume, so that a given set of molecules can be analyzed in all the cells within a larger tissue sample. Programmatic priority will be given to approaches that maximize the volume of tissue that will be analyzed while maintaining cellular resolution and high biomolecular content.??

Given the focus of HuBMAP on spatial analysis, Centers are expected to include at least three core assays as part of their project. The combination of these assays must be capable of robustly characterizing all the cells of human origin present in the tissues and their extracellular environment:

• Multiplexed Immunoassay this includes fluorescence and mass spectrometry techniques using well-validated affinity reagents that can accurately and reproducibility map a significant number of proteins at high spatial resolution in 3D.
• Single Cell Transcriptome Sequencing this includes unbiased spatially-resolved transcriptomics and multi-omics techniques that can deeply characterize the transcriptome of a large population of cells.
• High Spatial Resolution Assay this includes sequencing, microscopy and mass spectrometry techniques with near single cell resolution that provide complementary and specific molecular information to the first two assays. Assays may include analysis of other biomolecular classes, including DNA, lipids, metabolites, proteins and their modifications. Examples include FISH, Imaging Mass Spectrometry, 3D volumetric imaging and multi-omics approaches. If a spatially resolved sequencing approach is already proposed as the first assay, a third complementary assay is still required, or if the third assay proposed is a spatially resolved sequencing approach, then a compelling justification for the synergy should be included.

In addition, Centers may propose additional assays based on their expertise and use cases. Applicants are strongly encouraged to utilize other imaging technologies such as MRI, CT, and optical coherent tomography or to leverage collaborations and existing resources to build complete organ maps, identify regions of interest, and map important systemic features such as the vasculature tree. Programmatic priority will be given to Centers with a strong track record of generating high quality data using their proposed set of assays, an adaptive and realistic multiscale approach to building a reference atlas, a synergistic set of assays that will generate a comprehensive 3D map of the chosen organ and a strong approach for validating results and quality assurance.

Data Analysis, Accessibility and Security

Central to the purpose of the TMCs is the construction of a high-resolution atlas of a human organ containing molecular, cellular, and tissue-level spatial, functional, and/or temporal relationships that are searchable and scalable. The Center is expected to develop computational tools and analytical workflows for the construction of this atlas through the generation, visualization, and modelling of multi-dimensional maps from their proposed high content, multiparameter imaging and omics assays. Applicants should propose to use methods that have been demonstrated to generate high-quality data, to fuse the core assay data types together for joint analysis, to validate segmentation and definition of cell types and to test the rigor, reproducibility and robustness of data, algorithms and models.

Making data, metadata, software, and other digital objects open, findable, accessible, interoperable, and reusable (FAIR) and citable especially as our understanding of these concepts evolve over time are key to the success of the HuBMAP. Applicants are strongly encouraged to propose using modular and scalable solutions. Applicants are strongly encouraged to optimize or adapt existing standards and approaches and to create new ones only when required. Applicants are also strongly encouraged to optimize or adapt solutions from other communities that have tackled similar mapping challenges.

Data security encompasses confidentiality, data integrity, and availability. All three elements are important for the HuBMAP and TMCs and maintaining confidentiality of controlled access data is a particularly high priority. Confidentiality includes managing data access to maintain data security and make data accessible to authorized users only for authorized purposes. Data security protection and proper stewardship of human genomic, phenotypic, and other sensitive information stored and distributed by the TMCs are of the utmost importance. The Notice for Use of Cloud Computing Services for Storage and Analysis of Controlled-Access Data Subject to the NIH Genomic Data Sharing (GDS) Policy (?https://grants.nih.gov/grants/guide/notice-files/NOT-OD-15-086.html) allows investigators to perform genomic analyses on a cloud platform. The NIH security best practices and provisions (https://www.ncbi.nlm.nih.gov/projects/gap/pdf/dbgap_2b_security_procedures.pdf) should be implemented to protect the privacy and confidentiality of research participants and prevent unauthorized access to data. The applicant(s) are also expected to adopt policies and procedures for notifying NIH staff, and managing, and mediating any loss of data or compromise of data confidentiality. Centers should conduct regular audits of their data security and protection processes, which should be validated by third party independent assessments. The Precision Medicine Initiative's Data Security Principles Implementation Guide provides an example for auditing and data security protection processes?https://www.healthit.gov/sites/default/files/pmi_security_ig_v16-clean.pdf. Funded TMCs must adopt the current data sharing policies and data use agreements of the Consortium (see:?https://hubmapconsortium.org/policies/) and take other steps to protect the privacy of research participants while at the same time making data rapidly available.

Coordination and Collaboration

Successful applicants to this FOA will become members of the larger HuBMAP Consortium composed of investigators who have been funded in response to at least one of HuBMAP FOAs. The purpose of the Consortium is to enable groups to effectively collaborate with each other to maximize the chances of overall success of the program. In addition to completing the research goals outlined in their applications, successful applicants will be expected to work collaboratively with all members of the Consortium to contribute to developing SOPs, data and metadata standards, metrics for data generation, participate in cross-site studies, engage in cross-training, and guide development of data analysis and visualization tools that can be used by the broader scientific community. Further information about the Consortium can be found on their website:?https://hubmapconsortium.org/.

Given their central role in the Consortium, TMCs should be prepared to work closely with the other funded groups in the consortium and actively participate in consortium meetings, including the annual HuBMAP investigator meetings, regular teleconferences with Consortium members and NIH Staff for the duration of the funding cycle, as well as participate in at least 3 collaborative projects with other consortium members. Therefore, TMCs are asked to plan and budget for approximately 20% of their total budget for collaborative activities as part of their applications. Collaborative project activities may include benchmarking of similar methods across sites, comparison of adjacent tissue slices by complementary methods, development of common analytical pipelines or joint analysis of data from the same tissue across multiple donors. Applicants are encouraged to include details of potential activities as part of their applications; however, the final set of activities will be determined post-award through discussion with Consortium members and NIH staff.

NIH intends that the products of the TMCs be broadly available to the research community to establish the foundations for a human body map that other NIH programs and the international community to build upon; this includes methods, tools, reagents, biospecimens, datasets, and software. Centers will be expected to abide by Consortium policies such as assay and data standards; the rapid sharing of sharing data, methods, and standards; publication of data and results; partnerships and participation of similar projects and programs and sharing of resources. Milestones for biospecimens collection and data generation will be recognized once details have been submitted to the HIVE.?The robustness and reproducibility of experimental results are critical to the success of HuBMAP.?In some cases, conducting additional critical experiments will be important for assessing progress. Therefore, NIH Program staff, in consultation with the PD/PI, may modify or add experiments to be conducted during the duration of an award.

Tissue Mapping Center Structure

This FOA uses the multicomponent U54 mechanism. Each TMC application will be composed of a Data Analysis Core (DAC) and an Organ Specific Project (OSP). The DAC and OSP have well-defined and distinct functions as described below and should be synergistic without being highly inter-dependent. The overall budget should reflect the needs of the Center, though is expected to scale-up after the first year as the center generates more data and ramp down in the final year.

Overall:?The Center Director and staff will be responsible for general administrative duties and for coordinating activities within the TMC and sharing expertise and resources with the other TMCs. They will also be responsible for ensuring coordination with the HuBMAP Consortium and the wider research community. Data production by TMCs will be assessed for meeting goals and milestones at two-time points: 1) the point at which data passes QC metrics and is accepted for ingestion by the HIVE, and 2) data release to the research community. Likewise, biospecimen collection, preservation and quality management will be assessed in an analogous way. The leadership of the Center is responsible for ensuring relevant expertise is engaged at the appropriate time to meet the Center's goals and milestones. As part of their goals and milestones, TMCs should develop specific, quantitative, six-month milestones for collecting biospecimens, data generation, quality assessment and submission of data and metadata. The Center Director will also manage intra-and extra-consortium collaboration projects. Due to the highly multidisciplinary nature of these Centers and the focus on collaboration and expertise sharing, in addition to the PD/PIs, each Center must have a Program Manager with demonstrated experience and the ability to manage day-to-day aspects of the Center and understand diverse needs, people and projects.

Data Analysis Core:?The Data Analysis Core (DAC) will be responsible for data annotation, curation, and analysis of data generated by the Center. The DAC will be responsible for building an overall organ atlas from 3D tissue maps from the data generated by the Organ Specific Project, including the registration of the data with respect to anatomical references, image segmentation and analysis, identification and annotation of cell types and states and extracellular compartment, and preparing different data sets for sharing. The DAC will share these maps and underlying data with the HIVE, to enable it to build an atlas of maps in the context of the whole human body. The DAC is strongly encouraged to use existing software packages and analysis methods, such as R-based or Python-based solutions, that would enhance reproducibility and re-use where possible, and consideration should be given to containerize the entire pipeline. The DAC will work closely with the Center staff to submit data and metadata in common, interoperable formats to the HIVE so that it can be easily integrated and re-used. The DAC will also work with the HIVE to optimize its secondary analysis pipelines and the implementation of a Common Coordinate Framework and with the other TMCs and the HIVE to implement Consortium-wide open, data and metadata standards and schemas; data quality metrics, ontologies and data elements; integration of imaging and omics data; analytical tools for visualization, segmentation and annotation. Responsibilities of DAC include ensuring that data is collected and submitted to the HIVE conforming with the agreed policies and practices of the Consortium, including Standard Operating Procedures (SOPs), data and metadata format and standards, the use of Common Data Elements (CDEs) and the Consortium's data sharing policy. DACs are strongly encouraged to propose using modular and scalable solutions where information and data exchange with the HIVE is formalized using standard (and fully open) file formats; using Application Programming Interfaces (APIs) and standards like RESTful; adopting suitable Workflow languages; containerization for reproducibility, etc. Applicants are strongly encouraged to talk with the HIVE Infrastructure and Engagement Center to understand how their approaches fit with the current architecture.

Organ Specific Project: The Organ-Specific Project (OSP) will be responsible for generating high quality tissue maps using multiple assays for the chosen organ or organ system. These responsibilities include establishing and optimizing SOPs for collection, preservation and quality control of tissue; collecting relevant metadata including location and orientation of biospecimens; validation and benchmarking of assays; and generating high quality, high-content spatial data using multiple assays with metrics for data quality control, reproducibility, and normal variation. Assays should be capable of high-resolution, state-of-the-art molecular, cellular, and tissue-level characterization of biospecimens for the purpose of constructing multi-scale, multi-dimensional tissue maps. The OSP is expected to set up a framework for collecting high quality biospecimens from a diverse range of donors (including sex, age, race and ethnicity) in a consistent manner from human donors with a strong rationale for the sampling approach and collection of appropriate metadata that will enhance the utility of data. In order to maximize the utility of data generated by the Consortium, TMCs are strongly encouraged to have or to rapidly establish consents during the setup phase that (a) explicitly allow for open (non-restricted) data sharing for research, and (b) allow for sharing biospecimens with other HuBMAP-funded groups. The OSP will also work closely with the Data Analysis Core (DAC) on topics such as providing data in consistent formats, with enough metadata describing the origin and nature of the biospecimen, details of collection and pre-analytical processing, details of the assays performed, and any filtering of the data prior to map generation. The OSP in conjunction with the Center staff will also work closely with the HIVE later in the program to manage biospecimens, OSPs in other TMCs on SOPs, and the HIVE and the DACs on data and metadata standards and file formats. The OSP needs to be flexible in their data collection strategies such that new technologies introduced through technology development projects, or related atlas building projects might be quickly tested, validated, and adopted over the course of the award lifetime.

Plan for Enhancing Diverse Perspectives: The FOA is open to all investigators. Investigators who are currently not part of HuBMAP Consortia are especially encouraged to apply. One of the priorities of HuBMAP is to ensure as broad a representation of researchers as possible. This FOA requires a Plan for Enhancing Diverse Perspectives (PEDP) as part of the application (see below). Applicants are strongly encouraged to view the available PEDP guidance material on the HuBMAP website.

Technical Assistance Conference Call

All applicants are strongly encouraged to contact NIH Staff to discuss the alignment of their proposed work with the goals of this FOA and the HuBMAP Program. A Technical Assistance teleconference will be held for potential applicants from 12-1pm Eastern Time on October 1, 2021. NIH staff will be available to answer questions related to this FOA. Dial in information for the call is posted on the HuBMAP website and slides will be made available on the website for those unable to attend.? Dial in information for the call is posted on the HuBMAP website and slides will be made available on the website for those unable to attend.?A list of frequently asked questions (FAQs) related to the program are also posted on the website:?https://commonfund.nih.gov/hubmap/generalfaqs. The information session is open to all prospective applicants, but participation is not a prerequisite to apply.

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

Section II. Award Information

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

Section III. Eligibility Information

1. Eligible Applicants

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:

• Hispanic-serving Institutions
• Historically Black Colleges and Universities (HBCUs)
• Tribally Controlled Colleges and Universities (TCCUs)
• Alaska Native and Native Hawaiian Serving Institutions
• 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)

Local 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)

Federal Governments

• Eligible Agencies of the Federal Government - including the NIH Intramural Research Program
• U.S. Territory or Possession

Other

• 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 not 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.
  • 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.

2. Cost Sharing

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

3. Additional Information on Eligibility

Number of Applications

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, per 2.3.7.4 Submission of Resubmission Application. 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 2.3.9.4 Similar, Essentially Identical, or Identical Applications).

Section IV. Application and Submission Information

1. Requesting an Application Package

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.

2. Content and Form of Application Submission

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.

Letter of Intent

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:

Zorina Galis, Ph.D.
Telephone: 301- 435-0560
Email: [email protected]

Page Limitations

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

Instructions for the Submission of Multi-Component Applications

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

Overall Component

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.

SF424(R&R) Cover (Overall)

Complete entire form.

PHS 398 Cover Page Supplement (Overall)

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

Research & Related Other Project Information (Overall)

Follow standard instructions,

with the following additional instructions:

Other Attachments:

Plan for Enhancing Diverse Perspectives (PEDP)

In an "Other Attachment" entitled "Plan for Enhancing Diverse Perspectives," all applicants must include a summary of strategies to advance the scientific and technical merit of the proposed project through expanded inclusivity. The PEDP should provide a holistic and integrated view of how enhancing diverse perspectives is viewed and supported throughout the application and can incorporate elements with relevance to any review criteria (significance, investigator(s), innovation, approach, and environment) as appropriate. Where possible, applicant(s) should align their description with these required elements within the research strategy section. The PEDP will vary depending on the scientific aims, expertise required, the environment and performance site(s), as well as how the project aims are structured. The PEDP may be no more than 1-page in length and should include a timeline and milestones for relevant components that will be considered as part of the review. Examples of items that advance inclusivity in research and may be part of the PEDP can include, but are not limited to:

• Discussion of engagement with different types of institutions and organizations (e.g., research-intensive, undergraduate-focused, minority-serving, community-based).
• Description of any planned partnerships that may enhance geographic and regional diversity.
• Plan to enhance recruiting of women and individuals from groups traditionally under-represented in the biomedical, behavioral, and clinical research workforce.
• Proposed monitoring activities to identify and measure PEDP progress benchmarks; indication of willingness to participate in NIH evaluations of PEDPs.
• Plan to utilize the project infrastructure (i.e., research and structure) to support career-enhancing research opportunities for diverse junior, early- and mid-career researchers.
• Description of any training and/or mentoring opportunities available to encourage participation of students, postdoctoral researchers and co-investigators from diverse backgrounds.
• Plan to develop transdisciplinary collaboration(s) that require unique expertise and/or solicit diverse perspectives to address research question(s).
• Publication plan that enumerates planned manuscripts and proposed lead authorship.
• Outreach and planned engagement activities to enhance recruitment of individuals from diverse groups as research participants including those from under-represented backgrounds.

For further information on the Plan for Enhancing Diverse Perspectives (PEDP), please see: https://commonfund.nih.gov/hubmap/generalfaqs

Project/Performance Site Locations (Overall)

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.

Research and Related Senior/Key Person Profile (Overall)

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

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.

Budget (Overall)

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

• PD/PIs:?The Center Director must devote a minimum of 1.8 person months of effort to the Center through the individual components. For applications with multiple PDs/PIs, a minimum effort of 1.2 person-month is required for the Contact PD/PI and 1 person-month of effort per additional PD/PI is required.
• Program Manager: Based on the complexity of the HuBMAP, TMCs are strongly encouraged to include and budget for a full-time Program Manager to manage day-to-day operations and work with the Center team, the rest of the HuBMAP Consortium, and NIH staff to efficiently and effectively manage and coordinate the Centers' activities.
• Equipment:?If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.
• Travel:?Include travel costs for the Center Director and pertinent members of the Center to attend annual HuBMAP Consortium meetings and workshops.
• Collaborations:?Include funds equating to approximately 20% of the total requested budget for coordination and collaborative activities within the Consortium. These activities will be refined post award. These funds will be restricted and require NIH prior approval for use. A prior approval request will be required to re-allocate these funds to other activities.

PEDP Implementation costs: Applicants may include allowable costs associated with PEDP implementation (as outlined in the Grants Policy Statement section 7: https://grants.nih.gov/grants/policy/nihgps/html5/section_7/7.1_general.htm )

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.

PHS 398 Research Plan (Overall)

Specific Aims: The Specific Aims should be overarching, visionary and distinct from the aims of the individual components. Include a rationale and description of how each aim is consistent with and enhances the goals of the HuBMAP Consortium.

• Project Summary/Abstract: Provide an overview of the competitive advantages of the Center. Describe the vision and goals of the Center and how these contribute to accomplishing the overall goals of HuBMAP and will coordinate and collaborate with the rest of the consortium. Succinctly describe the tissue maps that will be generated and how they are synergistic with currently funded research.

Project Narrative: State how the reference map constructed within the Center will further knowledge of the relationship between tissue organization and function and the potential impact this may have on public health.? Briefly describe the relevance of the research products and resources to be generated by the Center activities for HuBMAP and the wider research community.

Research Strategy: The applicant must provide details of the center's vision and organization at a high level. In lieu of the standard Research Strategy sub-sections (Significance, Innovation, Approach), use the sub-sections defined below to present a concise overall vision and plan for the proposed TMC.

Center Research Strategy: Description and rationale for the major theme and structure of the Center, its goals and objectives, synergy with ongoing research and background information to provide feasibility of accomplishing these goals. The rationale and inter-connectedness between the tissues and organs chosen, the assays deployed, and between the cores and projects composing the Center should be clearly articulated. Describe the timeline and key milestones for the Center, highlighting when each Organ Specific Project will start and the rationale for this timing. Describe innovative aspects of the assays and how they will be integrated together for tissue mapping. Outline the significance and impact provided by the creation of these tissue maps and how the range of tissues and technologies will be expanded during the project. In addition, a vision for coordination and collaboration with the HuBMAP Consortium, as well as the greater research community and other key stakeholders must be described. Describe synergies and possible collaborations with other initiatives or the wider research community that would enhance the productivity of the Center. This FOA is not intended to support the development of new technologies, assays or models that are not well validated in mammalian tissues. However, because new and more powerful technologies are constantly emerging, describe a roadmap and methods for potentially incorporating them in later years.

Center Management Strategy: Without duplicating information in the biosketches, applicants should provide evidence of successful management of large, multi-component programs and prior experience with generating significant, high quality, imaging, and omics data as part of a Consortium. Describe the leadership team and how components of the TMC, including key personnel, will interact within the TMC itself and with the broader HuBMAP Consortium and NIH program staff. Describe prior experience in working as part of a research network or other large-scale collaborative activities to meet individual and group goals, including examples of such prior work. Describe how decisions will be made by the leadership team and carried out.

Center Coordination Strategy:?Provide an overview of the Center organization including coordination and interactions between the OSP and DAC and manage and coordinate communication, day-to-day activities, collaborations, and resource and data sharing with the HuBMAP Consortium and NIH program staff. Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating institutions. Describe how the Center Director will manage and coordinate communication, day-to-day activities, collaborations, and resource and data sharing within the TMC. Describe plans for assessing progress of the TMC to meeting its goals and milestones. Describe and, preferably, demonstrate through presentation of preliminary data strategies?how the components of the Center can work together to minimize confounding variables in data generation. Describe plans for collaborating with other HuBMAP sites and NIH program officials to design or improve Consortium operations and implement protocols. Describe plans to work with the HuBMAP Integration, Visualization and Engagement Collaboratory to optimize data collection and analysis strategies ? and facilitate public access to HuBMAP data through the HIVE including who will be accountable for data submission to the HIVE. Describe in detail the quantity and formats of the data, metadata, analytical products and tools that can be delivered by the TMC to the HIVE. Applicants should also describe plans for, and willingness to abide by the Material Use Agreements, Data Sharing Agreements and other policies already established by the Consortium.

Goals and Milestones: Applicants should define a clear set of bi-annual (6-month) milestones for the proposed project that are consistent with the goal of developing widely useable, high-quality tissue maps. Explain the overall strategy for achieving the goals and objectives of the Center and how the different components of the Center will interact to achieve these goals. Specifically, applicants must provide a timeline with details of how the Center will ramp-up data generation and analysis during the funding period. The applicant should also describe metrics associated with evaluating achievement of milestones and what action will be taken, and when, if a milestone is not met or significantly delayed.? Applicants should describe how they will prioritize their activities to ensure that the goals of the HuBMAP Program will be achieved. Milestones may be revised at the time of the award and yearly as described in the terms and conditions of a Cooperative Agreement.

Letters of Support: Provide any letters of support, as appropriate. Include any letters of support for the proposed Center by appropriate institutional officials.? Letters should address the commitment of the parent organization, or any of its partners, to the Center and its goals. The parent institution is expected to recognize the Center as a formal organizational component and provide documented evidence of space dedicated to the needs of the Center, protected time to devote to Center activities, staff recruitment, dedicated equipment, or other financial support for the proposed Center. The parent institution should provide assurance of its commitment to continuing support of the Center in the event of a change in directorship and a well-defined plan for this eventuality should be in place. Both the institution and pertinent departments must show a strong commitment to supporting the Center.

If collaborative linkages are being developed between the Center and other local NIH funded centers in related areas a letter of agreement from the collaborating Center PD(s)/PI(s) should be included. Do not provide letters of support from individuals who will not be involved in the Center's research activities.

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.

The following modifications also apply:

All applications, regardless of the amount of direct costs requested for any one year, must address a -Resource Sharing Plan.

• Data Sharing:?Implementation of FAIR (Findable, Accessible, Interoperable, Reusable) Principles is essential for the success of HuBMAP. Consistent with achieving these principles, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be rapidly deposited as appropriate into the HIVE and in a recognized and reusable format. The HIVE will serve as the central access point for information regarding data, tools, and reagents being developed by the HuBMAP Consortium. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://osp.od.nih.gov/scientific-sharing/genomic-data-sharing/) and should indicate their agreement to abide by it in the data sharing plan.
• Consortium Policies: Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the HuBMAP Consortium and approved by NIH staff (https://hubmapconsortium.org/policies/). A primary goal of the HuBMAP is to lay the foundation for a widely accessible atlas of tissue maps and this will require data and resources to be shared quickly and openly once validated, consistent with achieving the goals of the program. ?Restrictive licensing and sharing practices for HuBMAP-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of HuBMAP program data, tools, and resources for research purposes will be hindering the goals of the HuBMAP. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees will adhere to current and future policies, methods, and standards developed by the HuBMAP Steering Committee (SC), in concert with the NIH.?These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing. Prior to funding, NIH Program Staff may negotiate modifications to the Resource Sharing Plan with the applicant.
• Public Access:?The NIH Common Fund intends to maximize the availability of publications and the sharing of underlying data for HuBMAP Projects and encourages publication of preprints and the use of open access journals. Applicants should describe their proposed process for making resulting publications and to the extent possible, the associated data immediately and broadly available to the public or provide a justification if such sharing is not possible. Underlying primary data is expected to be made as widely and freely available as possible while safeguarding the privacy of participants and protecting confidential and proprietary data. Applicants are encouraged to use existing, open licensing approaches and preprint repositories, and may include anticipated charges for publication or data sharing and resources that may be needed to support a proposed Resource Sharing Plan in the budget plan of their application.
• Protocol, Tool, and Reagent Sharing:?As one of the primary goals of this program is to advance research through development, establishment, broad dissemination and use of community resources across the research community, NIH intends that protocols, tools, and reagents generated by the HuBMAP Consortium be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream investigations of understudied biomolecules by the larger scientific community. For all applications and where otherwise applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including models, protocols, biomaterials, and reagents. The HIVE will work with all HuBMAP Consortium investigators to collect, curate, and disseminate information regarding tools and reagents being developed by the HuBMAP Consortium to be disseminated through the HIVE and other sources as appropriate.
• Intellectual Property:?Intellectual property rights asserted by proposers must be aligned with the open source regime used to distribute software made under the award. Exceptions to open source technology will be considered only in compelling cases. Awardees will own the software and data developed under this award, subject to the Government’s royalty-free, nonexclusive, irrevocable right to use, disclose, reproduce, prepare derivative works, distribute copies to the public, and perform publicly and display publicly, in any manner and for any purpose, and to have or permit others to do so. In addition, inventions, technical solutions and methods developed under this solicitation will remain the property of the awardees, who may freely use them for their own commercial purposes, subject to a nonexclusive, nontransferable, irrevocable, paid-up license to the Government to practice, or have practiced for or on its behalf, the inventions, technical solutions and methods throughout the world. Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).
• Sharing Software:?Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others and to have a plan for versioning software. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution. There is no prescribed single license for software produced in this project; however, the terms of software availability should include the ability of researchers outside HuBMAP and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with HuBMAP and reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan. A software sharing plan guided by the following principles is thought to promote the largest impact:

• The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• To preserve utility to the community, the software should be transferable such that another individual or team can continue development if the original investigators are unwilling or unable to do so.

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.

PHS Assignment Request Form (Overall)

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

Data Analysis Core

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.

SF424 (R&R) Cover (Data Analysis Core)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Data Analysis Core)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Data Analysis Core)

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 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.

Project /Performance Site Location(s) (Data Analysis Core)

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.

Research & Related Senior/Key Person Profile (Data Analysis Core)

• 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 (Data Analysis Core)

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.

PHS 398 Research Plan (Data Analysis Core)

Specific Aims: State the Specific Aims of the Data Analysis Core describing how the DAC will assemble a reference atlas for the organ being studied by the TMC.

Research Strategy: Applicants should highlight aspects of the proposed activities of the DAC that speak to the significance and innovation of their approaches. In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Data Analysis Core using the sub-sections listed below. Describe the outputs from the TMC that will be submitted to the HIVE and the process for doing this in collaboration with the rest of the consortium.

Data Processing: Describe and demonstrate any existing or proposed data processing pipelines to be employed within the Center, specifically with regards to imaging and omics data collection. State how these pipelines might be scaled to meet the demands of increased throughput within the Center. State the degree to which the resulting processed data is interoperable and meets the qualifications for FAIR data sharing standards. If field standard pipelines are not being employed within the Center, provide justification for the use of in-house pipelines and provide examples of downstream analyses utilizing the output of the pipeline (to demonstrate interoperability). Describe a plan for assessing and management data quality including identification of missing or out of range data, calibration drift, or user variability.

Data Analysis: Describe and demonstrate the computational approaches to be employed within the DAC that will result in the generation of multiscale, multiparameter tissue maps as part of the atlas from high-content imaging and omics data from the OSP. As appropriate, describe strategies that will be used to integrate multiscale data from different spatial resolution assays; integrate disparate omics and imaging data types; automate image analysis to extract and annotate features; and systems biology approaches to connect disparate data.

Reference Atlas Construction: Describe and provide preliminary results demonstrating the feasibility of aggregating and integrating the datatypes proposed by the OSP to build a reference atlas. As appropriate, describe a multiscale approach that highlights how anatomical, microanatomical and cellular relationships will be combined into the atlas, how samples from the same individual and multiple individuals will be used to construct a parameterized canonical model,and how data from multiple assays will be used to construct a comprehensive map that includes intra- inter- and extra-cellular information across multiple molecular classes.

Consortium Coordination: Describe plans to work with the HIVE to submit data and other TMCs to jointly analyze data generated by the Consortium. Describe how proposed analysis workflows or pipelines compare with existing pipelines already used by the Consortium and plans for regular data submission to the HIVE.As appropriate, describe opportunities for analysis of data with existing members of the Consortium or the wider research community.

Letters of Support: Include any relevant letters of support, as needed. Do not provide letters of support from individuals who will not be involved in the Center's research activities.

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:

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.

PHS Human Subjects and Clinical Trials Information (Data Analysis Core)

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.

Organ Specific Project

When preparing your application, use Component Type Projects.

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

SF424 (R&R) Cover (Organ Specific Project)

Complete only the following fields:

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

PHS 398 Cover Page Supplement (Organ Specific Project)

Enter Human Embryonic Stem Cells in each relevant component.

Research & Related Other Project Information (Organ Specific Project)

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 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.

Project /Performance Site Location(s) (Organ Specific Project)

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.

Research & Related Senior/Key Person Profile (Organ Specific Project)

ASSIST will default to Project Lead . If you would like to use a different category, then replace Project Lead below with a different Category (e.g., Core Lead).

• 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 (Organ Specific Project)

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.

PHS 398 Research Plan (Organ Specific Project)

Specific Aims: State the specific aims for the Organ Specific Project and provide a rationale and description of how each aim addresses a specific aspect of generating tissue maps of that organ.

Biospecimen Management: Provide an overview of how the OSP will collect and analyze biospecimens in a manner that reflects the expected tissue diversity in order to build reliable tissue maps. Describe the type, volume,source and sampling approach for human biospecimen collection, including biological, technical and statistical justification. Provide details of the number of samples that can be acquired and processed each year, specifically stating how the accrual rate will contribute to the Interim and Overall Milestones. Provide details about the breadth of informed consent obtained from donors; biospecimens will potentially be analyzed or re-analyzed later in the Program using new and cutting-edge assays and data tools that will be introduced after award so careful attention must be paid to the design of donor consent forms at the time of specimen collection. Consent forms that allow for broad data sharing are strongly encouraged. Describe plans for collection of appropriate clinical and epidemiological data that will best inform construction and future use of the proposed tissue maps. Include details regarding what biospecimens can and will be shared through a Tissue Core along with details of metadata that will be collected, data standards, how information about location and orientation of tissues will be collected and preserved. Applications are encouraged to present preliminary data that demonstrates awareness of how sample quality can be maximized for a variety of downstream assays.

Pre-Analytical Pipeline: Provide a comprehensive roadmap for sample acquisition, processing, and characterization prior to analysis. Describe how the source, orientation and location of biospecimens will be determined and shared, including a plan for interoperability with other TMCs utilizing the Common Coordinate Framework developed by the Consortium. Describe any anatomical or pathological analyses that will be performed to characterize the specimen at the time of collection. Describe quality control metrics that will be developed and/or employe d to ensure high sample quality upon collection, after preservation, and upon pre-analytical processing, including parameters that define sample quality and a plan for sharing quality control measures and information with the Consortium. Describe how the tissue will be processed and/or preserved to facilitate analysis, including optimization of pre-analytical processing of tissue for multiple imaging and omics assays.

Characterization Pipeline: Provide a general overview of the assays that will be deployed and the various data types that will be collected to characterize the tissue. Provide a biological justification for data type, sampling approach and data volume to be acquired that is motivated by the maps to be constructed. Benchmark the sensitivity, specificity and reproducibility of the assays to be deployed and any strategies used to calibrate and optimize them. State if technologies proposed within the application can be considered analytically validated. If not, provide plans and timelines for analytical validation. Provide a workflow for data collection that describes how high-content, high-throughput data at a single cell resolution will be collected for comprehensive characterization of each biospecimen. If assays are in different geographical areas, provide a plan for how biospecimens will be divided or transported for analysis. Describe a strategy to monitor and ensure the quality of instrument performance and data generated across the Center. Applications should describe typical error rates for the proposed assays and steps for data quality management.

Scaling and Standardizing the Pipeline: Describe plans for how the data generation pipeline will be scaled up during the project, including expectations for different datasets to be generated such as preliminary data, calibration data, validation data, and production data. Provide an overview for how the proposed pipeline may be harmonized with those developed by other TMCs. Describe plans for scaling the pipeline including how emerging technologies may be incorporated into the pipeline, optimization of existing assays to enhance throughput or building additional analytical capacity.

Letters of Support: Include any relevant letters of support, as needed. Do not provide letters of support from individuals who will not be involved in the Center's research activities.

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:

Resource Sharing Plan 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.

PHS Human Subjects and Clinical Trials Information (Organ Specific Project)

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

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

3. Unique Entity Identifier and System for Award Management (SAM)

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

4. Submission Dates and Times

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.

5. Intergovernmental Review (E.O. 12372)

This initiative is not subject to intergovernmental review.

6. Funding Restrictions

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.

7. Other Submission Requirements and Information

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 fieldof 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, NIH. Applications that are incomplete or non-compliant will not be reviewed.

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.

Use of Common Data Elements in NIH-funded Research

Many NIH ICs encourage the use of common data elements (CDEs) in basic, clinical, and applied research, patient registries, and other human subject research to facilitate broader and more effective use of data and advance research across studies. CDEs are data elements that have been identified and defined for use in multiple data sets across different studies. Use of CDEs can facilitate data sharing and standardization to improve data quality and enable data integration from multiple studies and sources, including electronic health records. NIH ICs have identified CDEs for many clinical domains (e.g., neurological disease), types of studies (e.g. genome-wide association studies (GWAS)), types of outcomes (e.g., patient-reported outcomes), and patient registries (e.g., the Global Rare Diseases Patient Registry and Data Repository). NIH has established a Common Data Element (CDE) Resource Portal" (http://cde.nih.gov/) to assist investigators in identifying NIH-supported CDEs when developing protocols, case report forms, and other instruments for data collection. The Portal provides guidance about and access to NIH-supported CDE initiatives and other tools and resources for the appropriate use of CDEs and data standards in NIH-funded research. Investigators are encouraged to consult the Portal and describe in their applications any use they will make of NIH-supported CDEs in their projects.

Applications Involving the NIH Intramural Research Program

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 in the NIH Intramural Source Book.

Post Submission Materials

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.

Section V. Application Review Information

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.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the Centerto 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 Center that by its nature is not innovative may be essential to advance a field.

Significance

Does the Centeraddress 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 Center rigorous? If the aims of the 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?

Will this Center make a significant contribution to the overall goals and objectives of the Human BioMolecularAtlas Program? Will the data and knowledge generated by this Center be integrated into a reference atlas and lead to a better understanding of the relationship between tissue organization and function?

Investigator(s)

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the 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 Center 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 Center?

Do the PD(s)/PI(s) and research team have a strong track-record of generating, integrating and analyzing high-quality data as part of a consortium?

Does the research team have a strong expertise across all areas of the data generation pipeline and a clear leadership plan for integrating their expertise to meet the specific aims of the Center?

Is the leadership plan, including how decisions will be made across the Project and Resource Cores, appropriate?

Are the plans for communicating and collaborating with the HuBMAP Consortium and NIH staff appropriate and likely to facilitate overall program objectives?

Are administrative structures in place for the day-to-day management of the Center, including mechanisms for internal quality control of ongoing research?

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? 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?

This FOA is not intended to support the development of new technologies, assays or models. However, because new and more powerful technologies emerge in the field, are roadmap and methods for potentially incorporating them in later years sufficiently described?

Is the design of those roadmap and methods creative, innovative and likely to maximize the quality of the data generated?

Are the data analysis approaches innovative, state-of-the-art and likely to improve tissue collection strategies, assay choices and sampling approaches?

Approach

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the Center? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed Center? 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 Centeris 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?

Has the TMC proposed a pipeline for tissue collection and analysis that minimizes degradation, maximizes the quantity and quality of data generated? Are plans to increase the rigor and reproducibility of the data generation acceptable?

Has the Center proposed a suite of assays and approaches that are appropriate for the choice of organs and tissues to be examined? Are the assays complementary in the data they will generate?

Are the assays optimal and well-designed for spatially mapping human tissue in a high-content, high-throughput manner?

Will the research strategy effectively and efficiently result in tissue maps that comprehensively profile a significant number and diverse range of biomolecules present?

Does the plan provide ample opportunity for collaboration, integration, and interaction within the TMC, with the rest of the HuBMAP Consortium and the wider research community?

Is the timeline proposed for ramping up data production reasonable?

Is there synergy between the organ specific projects? Are there inter-dependencies between the OSPs that would prevent them progressing independently?

Are the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, reasonable and adequate for ensuring the rapid and open sharing of research resources generated by this Center: (1)Data Sharing Plan; (2)Sharing Model Organisms; (3)Genomic Data Sharing Plan (GDS) (4) Plan for Public Access; (5) Plan for Protocol, Tool, and Reagent Sharing; and (6) Plan for Sharing Software?

If the project 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 Centerproposed? Will the Centerbenefit from unique features of the scientific environment, subject populations, or collaborative arrangements?

Are the instrumentation and computational resources in place (or readily obtainable) and adequate to support the project? Are safeguards in place to protect donor personal identifiable information if relevant?

As applicable for the project 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.

Additional Review Criteria - Data Analysis Core

• Are the staffing, equipment, and other resources that are available to the DAC sufficient and relevant to meeting the goals?

Additional Review Criteria - Organ Specific Project

The Organ Specific Project should effectively and efficiently contribute to the overall objectives of the Center and HuBMAP. Reviewers should consider the review criteria below in determining the scientific merit of each OSP. Each assigned reviewer will provide one score for the OSP. The scientific merit of individual OSPs should be considered by reviewers in determining Overall Impact score for the Center.

• Is there adequate scientific and technical merit to justify the OSP?
• How does the OSP contribute to the overall objectives of the Center? Is the OSP essential to the mission of HuBMAP?
• Will the OSP likely achieve the throughput and content necessary to build maps that are reproducible and reusable?
• Are the staffing, equipment, and other resources that are available to the OSP sufficient and relevant to meeting the goals?

Protections for Human Subjects

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.

Inclusion of Women, Minorities, and Individuals Across the Lifespan

When the proposed Center 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.

Vertebrate Animals

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.

Biohazards

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.

Resubmissions

Not Applicable

Renewals

Not Applicable

Revisions

Not Applicable

As applicable for the 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.

Applications from Foreign Organizations

Not Applicable

Select Agent Research

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).

Authentication of Key Biological and/or Chemical Resources:

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.

Budget and Period of Support

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

Is the budget allocated to each of the components reasonable to support the proposed activities?

2. Review and Selection Process

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by convened by the 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 will receive a written critique.

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.

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 appropriate national Advisory Council or 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.
• Evidence that the applicant and investigators are committed to policies as established by the Consortium Steering Committee including confidentiality, publications, sharing of information and resources, and collaboration.
• Evidence of previous productive, cooperative, collaborative interactions as part of a Consortium.
• Evidence that the Center will contribute to the diversity of technical and intellectual approaches and to the overall goals of the HuBMAP program.

3. Anticipated Announcement and Award Dates

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.

Section VI. Award Administration Information

1. Award Notices

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

Recipients must comply with any funding restrictions described in Section IV.6. 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: Grantee 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 recipient 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: Generaland Part II: Terms and Conditions of NIH Grant Awards, Subpart B: Terms and Conditions for Specific Types of Grants, Recipients, and Activities, including of note, but not limited to:

• Federalwide Research Terms and Conditions
• Prohibition on Certain Telecommunications and Video Surveillance Services or Equipment
• Acknowledgment of Federal Funding

If a recipient is successful and receives a Notice of Award, in accepting the award, the recipient agrees that any activities under the award are subject to all provisions currently in effect or implemented during the period of the award, other Department regulations and policies in effect at the time of the award, and applicable statutory provisions.

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 and 2 CFR Part 200.206 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

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) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 2 CFR Part 200 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 recipients 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 recipients for the project, although specific tasks and activities may be shared among the recipients and the NIH as defined below.

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 HuBMAP Program and will participate as non-voting members in the Consortium committees. The HuBMAP WG is led by the HuBMAP Program Manager and co-chaired by the Directors of NIBIB, NHLBI, and NIDDK. 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.

HuBMAP Program Manager:?The HuBMAP Program Manager is an NIH extramural scientist who is responsible for overall coordination of the Consortium and chairs the NIH WG. They will have substantial involvement in assessing progress and making recommendations about future funding. The HuBMAP Program Manager will have substantial scientific programmatic involvement in the direction of all the HuBMAP awards and may consult other NIH and non-NIH experts in making determinations. They will participate as a non-voting member of all Consortium committees and will review and approve Consortium policies. The HuBMAP Program Manager will not co-author publications with project investigators.

HuBMAP Program Coordinator:?One or more NIH Program Staff will serve as Program Coordinators. The HuBMAP Coordinator will have substantial programmatic involvement that is above and beyond the normal stewardship role. The Coordinator will provide cooperation or coordination with, or assistance to, recipients in performing project activities. If feasible, the Coordinator will connect recipients with NIH-supported research resources and identify other researchers or resources that may accelerate the project. The Coordinator will also assist with connecting investigators to other federal agencies, similar consortia, and related fields of research. The Coordinator will not co-author publications with project investigators. ?

Steering Committee (SC):?The purpose of the SC is to recommend direction for the HuBMAP Consortium consistent with the program goals, develop Consortium policies and projects to build synergy and improve communication and collaboration between the projects, and 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 Team Leads 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 HUBMAP 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 HuBMAP Program Manager and the NIH Working Group for approval.

External Program Consultants (EPCs):?As part of the HuBMAP program, NIH staff will engage 5-10 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 HuBMAP Program or individual recipients as well as recommending changes in priorities for the HuBMAP 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 HuBMAP 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 HuBMAP Program as necessary. The assessments and recommendations will be provided through the NIH WG to the Director of the Office of Strategic Coordination, NIH

HuBMAP Consortium:? The HuBMAP Consortium is made up of HuBMAP recipients, 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 HuBMAP 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 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; discussing and approving milestones and significant changes to the project; and technical assistance to correct performance and facilitate interactions. The PO must approve in advance and in writing annual milestones and any significant changes to the award. The PO also has the option to recommend to the HuBMAP Program Manager, following consultation with the Project Scientist(s), ESCs or the NIH WG, restricting an award based on progress towards milestones, to incentivize rapid development and implementation of policies or collaboration between members of the consortium, or generation of data or resources for use by Consortium members or the wider community. 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. The Program Officer will not co-author publications with project investigators.

NIH Project Scientist(s) -?One or more NIH Program Staff will serve as Project Scientists (PSs), for each HuBMAP award and, as appropriate, to oversee collaborative projects amongst recipients and/or other Consortium members. The PSs will serve as the scientific representatives of the NIH to the investigators in accordance with the 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.? The PSs will provide substantial NIH scientific programmatic involvement with the awardee that is anticipated during the performance of the activities supported by this Cooperative Agreement, including review of milestones. 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.

PD(s)/PI(s) Responsibilities

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

• All aspects of the study, including any modification of study design, the 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.
• Recipient(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 and details of biospecimens are submitted in a timely fashion to the HIVE, 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 policies.
• Ensuring that software and other tools and resources developed as part of this project are made publicly available according to HuBMAP 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 EPCs for the purpose of scientific evaluation and use by other consortium members in collaborative projects.
• Recipient(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. At least one in-person SC meeting will be held per year, for which HuBMAP recipients 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 HuBMAP 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 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 the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH Staff Involvement

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 staff may have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

• NIH staff (HuBMAP Program Manager, HuBMAP Coordinator, Project Scientist(s) and Program Officer) have substantial programmatic involvement in oversight of project management.
• The Program Officer is the NIH point-of-contact for the project, except for special circumstances designated by NIH. The Program Officer will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. The Program Officer must approve in advance: (i) changes in the roster and effort of the PD(s)/PI(s) and key personnel, (ii) changes in the goals and milestones for the project, (iii) changes in the scientific scope of the project, (iv) changes to the frequency of business meetings, (v) changes in goals of collaborative projects, and (v) any exceptions to the Consortium's policies. The Program Officer will not co-author publications with project investigators.
• The Project Scientists(s) will provide 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(s) will keep the PD(s)/PI(s) informed of any issues and concerns involving the project and provide advice on how to address them. 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 and must be kept informed of all substantive deliberations and developments affecting the project. 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 HuBMAP Program Manager will work closely with the Program Officer and Project Scientist(s) to monitor the progress of the project and coordinate collaborative projects, resource sharing and outreach as part of the Consortium. The Program Manager will keep the PD(s)/PI(s) informed of consortium-wide activities, policies and issues. The HuBMAP Program Manager will not co-author publications with project investigators.
• NIH staff and their respective Institutes and Centers will manage Conflicts of Interest and Management of Bias as detailed in the NIH Policy Manual.
• Progress Reviews. The annual evaluation by the Program Officer and Program Manager will be based on the non-competing application and progress report, center records, and assessments by the Project Scientist(s). The Program Officer and Program Manager will review the management, performance, and utilization of the project. If concerns are identified by the Program Officer or Program Manager, the Project Scientist(s) will work with the PD(s)/PI(s) to develop plans to address them in the next year of support and. 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. In the event of long-term incapacitation of resource facilities, NIH may reduce the budget or term of support to phase out the project. Though the Cooperative Agreement mechanism does provide options for restricting, reducing, or terminating awards, it also provides options for interacting supportively with awardees to help ensure program success. Before any modifications are made, NIH staff will engage with the awardees in a positive manner and as allowed by the Cooperative Agreement mechanism to resolve performance issues where possible in a timely manner.?

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 HuBMAP Program Manager 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 the development of shared tools and collaborative projects; identifying opportunities for sharing techniques, materials, information and tools developed within each individual HuBMAP project; facilitating communication and fostering collaboration across the Consortium; reviewing the 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 HuBMAP 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 HuBMAP 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. Current working groups include:

• Policies
• Communication and Engagement
• Collaborative Project Planning and Publications
• Data Coordination Team
• Integrated Data Analysis & Interpretation
• Affinity Reagent (mAb) Imaging and Validation
• Common Coordinate Framework
• Data Curation

Dispute Resolution

Any disagreements that may arise in scientific or programmatic matters (within the scope of the award) between award recipients and the NIH may be brought to Dispute Resolution. A Dispute Resolution Panel will be convened. The panel will have three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, recipients 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. NIH FOAs outline intended research goals and objectives. Post award, NIH will review and measure performance based on the details and outcomes that are shared within the RPPR, as described at 45 CFR Part 75.301 and 2 CFR Part 200.301.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for recipients of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All recipients 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 the threshold. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113and 2 CFR Part 200.113 and Appendix XII to 45 CFR Part 75 and 2 CFR Part 200, 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 75and 2 CFR Part 200 Award Term and Condition for Recipient Integrity and Performance Matters.

Section VII. Agency Contacts

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)

General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]

Zorina Galis, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-435-0560
Email: [email protected]

Center for Scientific Review (CSR)
Email:?FOA [email protected]

Ann Marie Brasile-Mejac
National Heart, Lung and Blood Institute (NHLBI)
Telephone: 301-827-8016
Email: [email protected]

Section VIII. Other Information

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 and 2 CFR Part 200.