NIH’s new Application Submission System & Interface for Submission Tracking (ASSIST) is available for the electronic preparation and submission of multi-project applications through Grants.gov to NIH. Applications to this FOA must be submitted electronically using ASSIST or an institutional system-to-system solution; paper applications will not be accepted. ASSIST replaces the Grants.gov downloadable forms currently used with most NIH opportunities and provides many features to enable electronic multi-project application submission and improve data quality, including: pre-population of organization and PD/PI data, pre-submission validation of many agency business rules and the generation of data summaries in the application image used for review.

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) and where instructions in the Application Guide are directly related to the Grants.gov downloadable forms currently used with most NIH opportunities. Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

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

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

The 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;
• 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 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.

HuBMAP will scale-up the scope of tissues, technologies, data management and community engagement that are being addressed during the eight-year duration of the program. The program is expected to have four stages: a set-up phase in FY18, a scale-up phase in FY19-21, a production phase in FY22-24 and a transition phase in FY25. The five research initiatives that compose the program are:

• Transformative Technology Development - This set of initiatives, the first of which will be issued FY18, seeks to establish proof of principle and validation of the next generation of tools, techniques and methods that will be foundational for mapping the human body at high resolution.
• Rapid Technology Integration - This set of initiatives, which is expected to start in FY19 pending the availability of funds, will focus on nimble integration of promising imaging and omics technologies into HuBMAP that have the potential to enhance data collection and validation during the program, and expanding throughput, multiplexing or discrimination of different classes of biomolecules.
• Tissue Mapping Centers - These Centers, which will be initially funded in FY18, will 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 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.
• The HIVE - This multi-component collaboratory, which will be funded in FY18, will have responsibility 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, which is expected to start half way through the program pending the availability of funds, 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 and 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.

This FOA seeks to establish state-of-the-art Tissue Mapping Centers (TMCs) that will generate high-resolution, multi-parameter, 3D biomolecular maps of non-diseased human organs and organ systems. Successful centers will build, benchmark, and standardize a pipeline 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 these 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 the 4 years of funding, covering the setup and scale-up phases of the Program, the goal is to have high-resolution, multi-scale, multi-dimensional molecular, cellular and morphological maps for multiple organs and donors. If this goal is achieved, a separate competitive FOA is expected to be issued in FY22 to support the production phase of the program that will significantly expand the range of tissues, assays and throughput of the TMCs.

Challenges

The Centers funded by this FOA will receive funding for the duration of the setup (FY18) and scale-up (FY19-21) phases of the Program. Some of the key challenges that centers are expected to address during the setup phase include but are not limited to:

• Capturing and preserving tissue location and orientation during collection, for example by using common anatomical landmarks;
• 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 were appropriate.

Some of the key challenges that centers are expected to address in addition during the scale-up phase include but are not limited to:

• Integrating, automation, benchmarking and validation of imaging and omics assays;
• Characterizing and reducing technical variation of common assays between TMCs;
• Identifying and analyzing missing, incorrect or sparse data;
• Integrating, segmenting and annotating imaging and omics data to build multiplexed, multiscale tissue maps;
• Identifying and analyzing neighborhoods and microenvironments in tissues;
• Annotating and interpreting data with common ontologies by identifying cell type, state and spatial interactions between cells, and between cells and extracellular compartments;
• 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.

Biological Samples

Centers should have a vision and detailed plan for mapping multiple non-diseased human organs and tissues during the funding period. During the setup phase, Centers are encouraged to start by optimizing their pipeline by focusing on one organ or component of an organ system, while actively planning for expanding to multiple organs or a complete organ system during the scale-up phase. Applicants must be able to perform comprehensive characterizations of the quality of human biospecimens at high resolution and describe plans for biospecimen management and minimization of tissue degradation. With the introduction of each new tissue and organ, the TMCs should take the lead for establishing best practices for collection and preservation of that tissue. Centers should anticipate that a Tissue Core will be established in the second year of the program to provide coordination and tracking of biospecimens collected by the TMCs. The Tissue Core will work closely with the HIVE to operate the biospecimen management system for the Consortium, that will track and coordinate access to inventory and metadata as well as providing a web portal for viewing and requesting specimens, sample collection and preservation SOPs and consent documents. Centers are strongly encouraged to plan a prospective collection strategy, including collecting appropriate epidemiological and anatomical data alongside data on specimen collection (including information about anatomical landmarks that might aid in atlas construction) and pre-analytical processing, though centers may also propose including some work with retrospective samples of known provenance. Centers are strongly encouraged to identify robust biological and statistical rationales for sampling decisions from non-diseased human donors, for example whether to focus on intra-individual sampling, inter-individual sampling across the lifespan or within a genetic group, or temporal sampling. The TMCs collectively will establish Consortium-wide best-practices for collection and preservation of tissues for tissue quality control and assembly of specimen metadata for downstream interrogation and analysis. Centers are strongly encouraged to develop enrollment criteria that will minimize the risk of abnormal or degraded tissue and pursue broad donor consent for unrestricted sharing of data for research purposes to maximize the utility of biospecimens and data. Teams are encouraged to have strong scientific justification for their choice of tissues and to consider availability of high quality tissue, synergies with other initiatives, and matching technical expertise of specific tissues with general technology capabilities. 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.

NIH expects to fund at least one Center focused in each of the following areas: 1) discrete, complex organs, 2) distributed organ systems and 3) rare, dynamic or motile cell types and their microenvironments or tissue neighborhoods. Accordingly, applicants should be cognizant that a subset of proposed Organ Specific Projects may be funded based on programmatic priorities, and that Organ Specific Projects (OSPs) from multiple TMCs may be expected to work closely together around large, complex organs or systems.

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 of a tissue. A high content approach is one that maximizes identification of tissues 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 at once, 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. Approaches that maximize the volume of tissue that will be analyzed while maintaining cellular resolution and high biomolecular content are strongly encouraged.

This FOA seeks to support high resolution, high-content, high-throughput, cost-effective assays that generate high quality quantitative data for characterizing cells and the extracellular structures at high resolution which at the same time allows the capture of position and orientation information within the tissue and within the human body. The combination of these assays will be capable of robustly characterizing all the cells of human origin present in the tissues and their extracellular environment. Centers are expected to be able to characterize the spatial distribution of a significant number and variety of biomolecules using established techniques such as FISH, immunofluorescence and RNAseq, and are strongly encouraged to incorporate, optimize and validate emerging in situ assays that will generate complementary quantitative, high-content, high-throughput biomolecular data. The vision for the center, the choice of tissues to be analyzed and technical expertise should be used to justify the choice of assays employed. Although the focus of the TMCs should be on in-situ analysis of the biomolecular composition and morphology of tissue, it is expected that unbiased, dissociative techniques could be used to inform the in-situ analysis in an iterative fashion. Likewise, although the focus is on building quantitative biomolecular tissue maps of human tissues, TMCs can propose pipelines that integrate data sources that will enhance scientific understanding, including from but not limited to MRI, micro-CT, photoacoustic imaging, Raman spectroscopy, histology, mechanical imaging, ATAC-seq, Hi-C, imaging cytometry and mass spectrometry.

Coordination and Collaboration

Successful applicants to this funding opportunity announcement 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. A Steering Committee (SC) composed of all the funded principal investigators and NIH staff will develop and implement Consortium policies, and guide overall direction of the Consortium to meet the goals of the program. This Steering Committee will meet regularly and be complemented by an Executive Committee and a set of working groups. NIH staff will also recruit outside experts (non-awardees) as External Program Consultants (EPCs) to provide advice directly to NIH.

As the primary source of data in the Consortium, the TMCs are expected to work closely together to establish best practices for data generation, carryout cross-site comparisons and engage in joint analysis activities. TMCs will need to work closely with each other and the HIVE to: (1) make sure their pipelines are interoperable, reproducible and meet the goals of the Program and policies of the Consortium, (2) that the data from the assays can be integrated and aligned across the human body, and (3) collaborate with other Consortium projects and the wider research community on QA/QC, standards, ontologies and to respond to community feedback. They will also work closely with the HIVE to develop and implement data and metadata standards, develop the framework for building an integrated atlas that integrates all the maps in the context of the human body, and making data generated by the Consortium interoperable and reusable. TMCs are strongly encouraged to reuse and adapt existing and widely-used data and metadata standards, ontologies, schemas, and formats, and to use common data elements, machine readable formats, structured reports and to minimize human data entry where possible. It is envisaged that TMCs will consist of a highly multidisciplinary team with expertise in areas including, and is not limited to: pathology, clinical and microscopic imaging, image analysis, sequencing, molecular and cellular biology, bioinformatics, data science, biostatistics, systems biology, and mathematical modeling. Given their central role in the Consortium, TMCs are encouraged to plan for mobility of researchers within the Consortium, either hosting researchers from other sites, or travelling to other sites to enhance collaboration. TMCs should also be prepared to work closely with the Rapid Technology Integration projects, that will start in FY19, to develop, test and potentially integrate innovative technologies into their production pipelines. All HuBMAP investigators will also be required to attend the initial Kickoff meeting in Fall 2018, the annual HuBMAP investigator meetings, regular teleconferences with Consortium members and NIH Staff for the duration of the funding cycle. Therefore, TMCs should plan for and propose collaborative projects and Consortium activities.

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 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 Tissue Core and 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.

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 methods that provide spatial data information regarding the organization of cellular and non-cellular tissue components;
• Projects proposing to primarily study fluids or dissociated cells; or
• Projects that do not propose all the required components of the TMC organization described below.

This FOA uses the multicomponent U54 mechanism. Each TMC will be composed of a Coordination Core, Organ Mapping Projects for each tissue type proposed and a Data Analysis Core. A Center may propose up to four Organ Specific Projects, and are encouraged to consider staggering the introduction of these projects to scale based on prior experience, preliminary results, resources and personnel, and synergy with other projects. Each core and project should have a well-defined and distinct function as described below and be synergistic without being highly inter-dependent. The cores and projects may vary in size, start date and composition depending on the needs of the project, but should be integrated to achieve the overall goal of the Center. The proposed budget should reflect the needs of the Center, though is expected to scale-up after the setup phase based on the number of organ specific projects, and as consortium activities begin. Center staff should have a strong track-record of producing high-quality data as part of a consortium.

Coordination Core: The Coordination Core (CC) will be responsible for general administrative duties and for coordinating activities within the TMC and sharing expertise and resources with the other TMCs. The CC 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 CC 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, annual milestones for collecting biospecimens, data generation, quality assessment and submission of data and metadata. Due to the highly multidisciplinary nature of these Centers and the focus on collaboration and expertise sharing, the lead for the CC must have demonstrated experience and the ability to lead, manage and understand diverse needs, people and projects.

Data Analysis Core: The Data Analysis Core (DAC) will be responsible for data annotation, curation, and analysis. The DAC will be responsible for building 3D tissue maps from the data generated by the Organ Specific Projects, 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, consideration should be given to containerize the entire pipeline. The DAC will work closely with the CC to submit data and metadata in common, interoperable formats to the HIVE Center 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. The DAC will also work closely with the other TMCs and the HIVE to develop and 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 practices and principles of the Consortium, including Standard Operating Procedures (SOPs), Common Data Elements (CDEs) and the Consortium's data sharing policy. In addition, each individual Data Analysis Core will be responsible for cross-validation of assays within and across TMCs and interpretation of data generated by that TMC.

Organ Specific Project: An Organ-Specific Project (OSP) will be responsible for generating high quality tissue maps using multiple assays for one organ or component of an organ system. A Center can propose up to four distinct and synergistic OSPs, with each focused on a separate organ or component of an 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 OSPs are expected to set up a framework for collecting high quality biospecimens 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 establish consents during the setup phase that (a) explicitly allow for open (non-restricted) data sharing and (b) allow for sharing samples with other HuBMAP-funded groups. The OSPs will also work closely with the Data Analysis Core (DAC) on topics such as providing data in consistent formats, with sufficient 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 OSPs in conjunction with the CC will also work closely with the Consortium-wide Tissue Core 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 OSPs 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.

Data Accessibility

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 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 should articulate how their approach is open and modular in nature and will not create undue burdens on the HIVE or other components of the HuBMAP.

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. TMCs must establish appropriate data sharing policies and data access procedures, and take other steps to protect the information of research participants while at the same time making sharing it rapidly with the rest of the Consortium. It is expected that a common set of policies that promote accessible will be adopted by the whole Consortium.

Data Security

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 is 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 (Ref: 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 develop 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 its 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

Applicants are encouraged to review and consider federal data security regulations. This includes adopting and implementing the policies, procedures, controls, and standards of the HHS Information Security Program to ensure the integrity, confidentiality, and availability of information. The HHS Information Security Program is outlined in the HHS Information Security Program Policy, which is available on the HHS Office of the Chief Information Officer’s (OCIO) Website, http://www.hhs.gov/ocio/index.html. Applicants are also encouraged to consider Federal Information Management Security (FISMA) security requirements including, but not limited to, preparation of an IT Security Plan, IT Risk Assessment, FIPS 199 Assessment, and performance of security control testing and evaluation. Furthermore, applicants using a commercial cloud are encouraged to have an understanding of FedRAMP requirements (http://www.fedramp.gov) and describe an approach for building a security assessment framework.

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 in January 2018. NIH staff will be available to answer questions related to this FOA. Time, date, and dial in information for the call will be announced in an NIH Guide Notice and will be posted on the HuBMAP website: https://commonfund.nih.gov/HuBMAP. A list of frequently asked questions (FAQs) related to the program will also be posted on the website. 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.

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

Higher Education Institutions

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

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

• 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)

Governments

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

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations
• Non-domestic (non-U.S.) Entities (Foreign Institutions)

Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (formerly CCR) 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 and SAM registration in order to complete the eRA Commons registration. Organizations can register with the eRA Commons as they are working through their SAM or Grants.gov registration. 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.

Given the multidisciplinary expertise required for exemplary response to the goals of the HuBMAP, this FOA encourages the use of the multi-PD/PI mechanism

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

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

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

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

A button to access the online ASSIST system 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.

Most applicants will use NIH’s ASSIST system to prepare and submit applications through Grants.gov to NIH. Applications prepared and submitted using applicant systems capable of submitting electronic multi-project applications to Grants.gov will also be accepted.

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.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

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:

Richard Conroy, Ph.D.
Office of Strategic Coordination / NIH Common Fund
Division of Program Coordination, Planning, and Strategic Initiatives
Office of the NIH Director
6001 Executive Blvd, 8180E
Bethesda, MD 20892
Telephone: 301-402-1486
Email: HUBMAP@mail.nih.gov

Component Types Available in ASSIST	Research Strategy/Program Plan Page Limits
Overall	6
Admin Core (Use for Coordination Core)	6
Core (use for the Data Analysis Core)	6
Project (use for each Organ Specific Project)	12

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

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

The application should consist of the following components:

• Overall: required
• Coordination Core: one required; maximum of 1
• Data Analysis Core: one required; maximum of 1
• Organ Specific Projects: required; minimum of one, maximum of four

When preparing your application in ASSIST, use Component Type Overall .

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

Complete entire form.

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

Follow standard instructions.

Facilities and Other Resources: Applicants should briefly describe the relevant institutional environment which would facilitate the effective implementation of the proposed Center. Applicants should also describe existing or planned resources that would be available to the TMC.

Enter primary site only.

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

Include only the Project Director/Principal Investigator (PD/PI) and any multi-PDs/PIs (if applicable to this FOA) for the entire application. The Center Director must demonstrate leadership ability and skills to direct a large multi-component project as part of a larger Consortium. The Center Director should also have extensive experience with imaging and omics assays.

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

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

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

Specific Aims: State the overall goals for the TMC:

Project Summary/Abstract: Provide an overview of the structure of the Center. Describe the vision and goals of the Center and how these contribute to accomplishing the overall goals of HuBMAP. Succinctly describe the tissue maps that will be generated.

Project Narrative: State how the maps 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.

The Specific Aims should be overarching, at a high level and distinct from the aims of the individual components.

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, and background information to provide feasibility of accomplishing these goals. The rationale and synergy 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 for the Center, highlighting when each Organ Specific Project will start and the rationale for this timing. Succinctly describe the synergy between cores and projects. Describe innovative aspects and synergy of the assays 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. Since these projects will be funded during the setup and scale-up phases of the HuBMAP program, applicants may briefly highlight how the Center will lay the groundwork for longer-term plans, including how the work may be expanded to include additional types of data and a wider range of organs and donors. 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.

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. In addition, the overall strategy should describe how the skills of individual team members will translate into the collective capability of the center, how the team brings complementary multidisciplinary scientific expertise required for the integration of multidimensional, multiparametric data and how the diverse expertise of the team members increases the capability for innovation, the ability to anticipate new directions, and the flexibility to redirect research when needed.

Goals and Milestones: Applicants should define a clear set of annual 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 the how 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 below.

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, with the following modification:

All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan. 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. 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. 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 considered to 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, through the HuBMAP Steering Committee (SC), will develop such policies, methods, and standards 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 Sharing Plan with the applicant.

Specific Plan for Public Access: The NIH Common Fund intends to maximize the availability of publications and the sharing of underlying data for HuBMAP Projects. Applicants should describe their proposed process for making resulting publications and to the extent possible, the underlying primary 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.

Specific Plan for 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://gds.nih.gov/) and should indicate their agreement to abide by it in the data sharing plan.

Specific Plan for 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 proteins 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).

Specific Plan for Sharing Software: Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. 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, 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 in the event that the original investigators are unwilling or unable to do so.

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. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software.

Appendix:

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 NIH-defined human subjects research, clinical research, or clinical trials (and when applicable, clinical trials research experience) 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

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

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

When preparing your application in ASSIST, use Component Type Admin Core.

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

Complete only the following fields:

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

Enter Human Embryonic Stem Cells in each relevant component.

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

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

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

List all performance sites that apply to the specific component.

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

• In the Project Director/Principal Investigator section of the form, use Project Role of Other with Category of Coordination Core Lead and provide a valid eRA Commons ID in the Credential field.
• In the additional Senior/Key Profiles section, list Senior/Key persons that are working in the component.
• Include a single Biographical Sketch for each Senior/Key person listed in the application regardless of the number of components in which they participate. When a Senior/Key person is listed in multiple components, the Biographical Sketch can be included in any one component.
• If more than 100 Senior/Key persons are included in a component, the Additional Senior Key Person attachments should be used.
• Describe the previous experience, if any, of the Coordination Core Lead in managing or participating in large-scale collaborative programs involving coordination of data generation across multiple projects

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

Personnel: The Center Director must devote a minimum of 1.8 person-months of effort to the Center through the life of the award. For applications with multiple PDs/PIs, a minimum effort of 1.2 person-months is required for the Contact PD/PI and 1 person-month of effort per additional PD/PI is required. Based on the complexity of these Centers during the scale-up phase, applicants are expected to propose and budget for a Center Administrator to manage day-to-day operations.

Travel: Include travel costs for the Center Director and pertinent members of the Center to attend annual HuBMAP Consortium meetings and workshops. The first Consortium meeting is expected to occur in the Fall of 2018.

Collaboration: Identify funds that will be for coordination and collaborative activities within the HuBMAP Consortium and with the wider research community. It is expected that these activities will be refined post award when the Consortium is established. Applicants are encouraged to identify costs associated with their Resource Sharing Plan, such as costs associated with training on using the shared resources.

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

Specific Aims: State the specific aims for the Coordination Core and provide a rationale and description of how each aim enhances the operation of the Center and its value to the HuBMAP Consortium.

Research Strategy: In lieu of the standard Research Strategy sub-sections (Significance, Innovation, Approach), use the sub-sections defined below to explain how the Coordination Core will effectively administrate and coordinate the Center's activities:

Leadership Plan: 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. Describe mechanisms to ensure internal effective management of ongoing research activities across the Center and participation in Consortium activities such as teleconferences, development of SOPs etc. Describe how synergy and integration within the Center and with the other TMCs will be fostered.

Center Coordination Plan: Provide an overview of the Center organization including coordination and interactions between the TMC OSPs and Cores. Describe the lines of responsibilities, including, as applicable, the effort distribution across the participating institutions. Describe how the Coordination Core 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 meetings 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.

Consortium Coordination Plan: Describe how the Coordination Core will manage and coordinate communication, day-to-day activities, collaborations, and resource and data sharing with the HuBMAP Consortium and NIH program staff. 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 HIVE 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. Describe plans for collaborating with other TMCs on topics including but not limited to SOPs, assay protocols, consent materials and data analysis. State willingness to adhere to Consortium-wide policies and procedures established by the NIH and the HuBMAP Steering Committee, including data access, publication, and intellectual property policies. Applicants should also describe plans for, and willingness to abide by, Memoranda of Understanding and other sharing agreements potentially needed for data and biospecimen sharing within the Consortium and other related programs.

If external Advisor/Consultants are needed, describe their qualifications and function. Do NOT provide names or biosketches for Advisors/Consultants.

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:. A Resource Sharing Plan should only be included in the Overall component.

Appendix:

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 (Coordination Core)

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.

When preparing your application in ASSIST, 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 tissue maps from the OSPs and upload data to the HIVE.

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 Unit 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 CC.

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 from high-content imaging and omics data from the OSPs. 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.

Map Construction: Describe and demonstrate plans to aggregate and integrate data and metadata from the broad range of experimental and computational approaches outlined throughout the application to build 3D tissue maps. As appropriate, describe how anatomical relationships will be maintained with respect to the donor's body, how samples from the same individual or multiple individuals can be analyzed to understand variability, how ontologies, visualization and image analysis tools will be used to interpret that data and build an atlas of different types of maps. Describe plans to develop or adapt computational tools for searching, cross-validation, and data visualization. Describe plans for how data analysis and map generation can optimize the data generation pipeline of the OSPs.

Consortium Coordination: Describe plans to work with the HIVE and other TMCs to develop common data formats and interoperable tools and procedures allowing seamless integration and presentation of the maps generated by the Consortium. Include preliminary plans for coordinating data quality across the Consortium. Describe how proposed analysis workflows or pipelines can be shared and harmonized across the Consortium. Demonstrate through evidence of collaboration and/or open source algorithm and computational tool development the flexibility of the DAC to incorporate disparate data types from emerging technologies incorporated after award. Analytical flexibility is an important aspect because the breadth of data types across the Consortium and technologies that may be employed in the future is currently unknown.

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: Resource Sharing Plans should only be included in the Overall component.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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.

When preparing your application in ASSIST, 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)

• 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.

Research Strategy: Applicants should highlight aspects of their proposed activities that speak to the significance and innovation of the approach. In lieu of the standard Research Strategy subsections (Significance, Innovation, and Approach), describe the activities of the Organ Specific Project using the sub-sections listed below.

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 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 a common coordinate system. Describe any anatomical or pathological analyses will be performed to characterize the specimen at the time of collection. Describing any sampling approaches employed. Describe quality control metrics will be developed and/or employed 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. Describe the reproducible, quantitative, and sensitive 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 high 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: Letters of support should be included from collaborators whose technologies or resources will be utilized by TMC but are not part of the investigative team. If the application includes discounts or other special consideration from vendors, letters of support stating that commitment should be included.

Resource Sharing Plan: Resource Sharing Plans should only be included in the Overall component.

Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

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

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.

Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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

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

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

Important reminders:

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

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

See more tips for avoiding common errors.

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

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 PDs/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 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. The intramural project should be added as a separate component to the parent application.

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.

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

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research 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 center to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the center proposed).

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

Does the center address an important problem or a critical barrier to progress in the field? Is there a strong scientific premise for the project? 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 BioMolecular Atlas Program?

Will the data and knowledge generated by this Center lead to be a better understanding of the relationship between tissue organization and function?

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 project is collaborative or multi-PD/PI , do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?

Do the Center Director and PD(s)/PI(s) have the appropriate experience in managing complex, multi-site projects involving teams of scientists?

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 strong expertise across all areas of the data generation pipeline and a clear leadership plan for integrating their expertise that will enhance the likelihood of success?

Does the leadership plan include details about how decisions, intellectual property, and communication across the Projects and Cores and with the rest of the HuBMAP Consortium etc. and will it make the Center operate more harmoniously and efficiently?

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?

Does the project have an optimal balance in proposing state-of-art, cutting-edge technologies and approaches that are also proven, validated and reliable so as to meet the high content and high throughput expectations for these Centers?

As new and more powerful technologies emerge in the field, is the research team poised to recognize when these new technologies are sufficiently developed and validated for incorporation into the pipeline?

Is the design of the pipeline creative, innovative and likely to take maximum 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?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the 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 project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?

If the center involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?

Has the TMC proposed an integrated pipeline for tissue collection that maximizes the quantity and quality of data generated? Is there appropriate quality control for tissue collection and data generation? Is there feedback to iteratively optimize and improve the pipeline?

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? Is there synergy between the assay choices?

Are plans to increase the rigor and reproducibility of the data generation acceptable?

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

Will high-risk aspects of the analysis be managed appropriately? Are potential problems, alternative strategies, and benchmarks for success presented?

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?

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

Are the resources, equipment and infrastructure available and in place (or readily obtainable) to achieve the required output from the screening and analysis pipeline?

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

• Are the Core leads, collaborators, and other researchers well suited to the goals of the Coordination Core?
• Are the staffing, equipment, and other resources that are available to the CC sufficient and relevant to meeting the goals? Is the budget allocated to the CC reasonable to support the proposed activities?
• Are the plans for communicating and collaborating with the HuBMAP Consortium and NIH staff appropriate and likely to facilitate overall program objectives?
• Are the plans for submitting data, protocols, and making resources available to the HuBMAP Consortium acceptable?
• Will there be coordination, communication, cohesiveness and synergy among the components of the TMC as they relate to achieving the overall objectives of the Center?
• Are mechanisms proposed for regular communication and coordination among investigators in the Center?
• Are administrative structures in place for the day-to-day management of the Center, including mechanisms for internal quality control of ongoing research?
• Are the staffing, equipment, and other resources that are available to the CC sufficient and relevant to meeting the goals? Is the budget allocated to the CC reasonable to support the proposed activities?

As applicable for the core 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.

• Are the Core leads, collaborators, and other researchers well suited to the goals of the Data Analysis Core?
• Are the staffing, equipment, and other resources that are available to the DAC sufficient and relevant to meeting the goals? Is the budget allocated to the DAC reasonable to support the proposed activities?
• Are statistical analyses, procedures, and policies adequate, appropriate, and consistent with accepted standards?
• Is there a strong scientific premise for the range of data processing, analysis, and computational modeling proposed?
• How well do the preliminary data demonstrate the range of data processing, analysis, computational modeling, and visualization approaches proposed, including any data processing, analysis and visualization algorithms that are not field standards?
• How well do the plans of the Data Analysis Unit ensure that data and algorithms are interoperable and meet the qualifications for FAIR data-sharing standards?

Organ Specific Projects 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 each OSP. The scientific merit of individual OSPs should be considered by reviewers in determining Overall Impact score for the Center.

• Does the OSP contribute substantially to the overall objectives of the Center and complement the other OSPs? Is the OSP essential to the mission of the Center and HuBMAP?
• Are the Project leads, collaborators, and other researchers well suited to the goals of the OSP?
• Are the staffing, equipment, and other resources that are available to the OSP sufficient and relevant to meeting the goals? Is the budget allocated to the OSP reasonable to support the proposed activities?
• Is the biospecimen collection roadmap proposed based on strong scientific rationale?
• Is there a sound plan for high quality prospective biospecimen collection, processing, and storage, and for obtaining high quality clinical and epidemiological information? Does the accural of biospecimens match plans for data analysis?
• Will the proposed quality assurance and quality control plans facilitate distribution of high quality biospecimens to the OSPs and the rest of the HuBMAP Consortium?
• Is there a strong scientific premise for the multidimensional, multiparameter data collection proposed?
• Do the preliminary data demonstrate the capabilities of the OSP to rapidly deploy the proposed molecular, cellular and tissue-level characterization assays?
• Will the proposed quality assurance and quality control plans facilitate successful molecular, cellular, and tissue level characterization of biospecimens?
• If the investigators propose technologies for biospecimen analysis that have not been analytically validated, will the technologies be fully validated and capable of contributing data generated by the Center within the proposed timeframe?
• 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? Is the budget allocated to the OSP reasonable to support the proposed activities?

For research that involves human subjects but does not involve one of the six 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 six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed 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 children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

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

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

Not applicable.

Not applicable.

Not applicable.

As applicable for the 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.

Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan , 4) Plan for Public Access, 5) Plan for Protocol, Tool, and Reagent Sharing, 6) Plan for Sharing Software.

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

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s), convened by 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:

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

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

Applications will be assigned on the basis of established PHS referral guidelines 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 with regard to 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.

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

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. 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. HHS provides general 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 http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. 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. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. 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 http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, and other HHS, PHS, and NIH grant administration policies.

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

• 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.
• 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 to provide a forum for discussing progress, challenges and opportunities for the Consortium. The SC will include PDs/PIs of each of the awards and NIH WG members. The SC will be chaired by two PD/PIs that are nominated by the SC and 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 awardees 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 agreement to a confidentiality policy. NIH is solely responsible for appointing the EPCs. The EPCs will meet at least twice a year, once in conjunction with the annual investigators meeting. The 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 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 will be made up HuBMAP awardees, the NIH WG and other scientists and groups the SC agrees to include within the Consortium. The Consortium structure is meant to efficiently and effectively guide all the funded projects to meet the overall goals of the 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) will provide the standard programmatic oversight and stewardship of the projects, including review of pre-award and award documents/requirements, review of progress reports and budgets, and any other programmatic issues that may arise.

The PO has the option to recommend to the HuBMAP Program Manager, following consultation with the project staff, ESCs and the NIH WG, the withholding or reduction of support from any project that substantially fails to achieve its goals according to the milestones agreed to at the time of the award. NIH reserves the right to withhold funding or curtail an award in the event of: (a) Substantive changes in the project, or failure to make sufficient progress toward the project milestones, including timely pre-publication deposition of data or reagents in accordance with approved Consortium Policies; or (b) ethical or conflict of interest issues.

• NIH Project Scientists

One or more NIH Program Staff will serve as Project Scientists (PSs), for each HuBMAP award and, as appropriate, to oversee collaborative projects amongst awardees and/or other Consortium members. The PS will serve as the scientific representative of the NIH to the investigators in accordance with policies and procedures of the cooperative agreement mechanism. If there is more than one PS, one of them will be designated as the Lead PS. 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.

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

• All aspects of the study, including any modification of study design, conduct of the study, quality control, data analysis and interpretation, setting project milestones, preparation of publications, and collaboration with other investigators, unless otherwise provided for in these terms.
• Awardee(s) will provide goals and progress toward those goals at regular intervals as requested by NIH staff and ensure that the data produced meets the quality standards agreed to by the Consortium
• Awardee(s) will ensure that the data are submitted to the HIVE, that details of biospecimens are submitted to the Tissue Core, 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
• 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.
• Awardee(s) will agree to accept close coordination, cooperation, and participation of NIH staff in those aspects of scientific and technical management of the project as described under "NIH Program Staff Responsibilities."
• Agreeing to the governance of the Consortium through the SC and the NIH WG, including accepting approved recommendations from the EPCs.
• Actively participating in the SC, including attending both in-person and teleconference meetings, and participating in collaborative activities and subcommittees. At least one in-person SC meeting will be held per year, for which HuBMAP awardees will pay the travel for their attending members.
• 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 -- including those regarding intellectual property, data and software release, publication of HuBMAP Consortium papers, quality control metrics, standardization, metadata requirements, 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.
• 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.

Areas of Joint Responsibility include:

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 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.
• 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.

It is anticipated that multiple subcommittees may need to be formed, for example, to address topics such as:

• Data and Reagent Deposition and Sharing
• Quality Control and Validation
• Publications and Outreach

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, 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)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726
Email: support@grants.gov

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: GrantsInfo@nih.gov (preferred method of contact)
Telephone: 301-945-7573

Zorina Galis, Ph.D.
National Heart, Lung and Blood Institute (NHLBI)
Email: HUBMAP@mail.nih.gov

Richard Conroy, Ph.D.
Office of the Director (OD)
Telephone: 301-435-9008
Email: HUBMAP@mail.nih.gov

David Balasundaram, Ph.D.
Center for Scientific Review
Telephone: 301-435-1022
Email: balasundaramd@csr.nih.gov

Tracee Foster
National Heart, Lung, and Blood Institute (NHLBI)
Telephone: 301-827-8030
Email: tracee.foster@nih.gov

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.