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

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

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

The 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.

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 vision for the HIVE is that it will: 1) manage the data generated by the Consortium, 2) coordinate internal and external Consortium activities, 3) develop novel tools for visualizing, searching and modelling data and 4) build an atlas of tissue maps. When fully realized, the HIVE will be the central hub of a collaborative community and data framework for comprehensively mapping the human body at high resolution. This goal will be achieved in close collaboration with the HuBMAP Consortium, other programs and the worldwide research community to develop a platform that hosts an interactive set of human tissue maps in the spatial framework of the human body. Users of the HIVE will be able to access, search, query, visualize, and model these 3D biomolecular maps to better understand the relationship between tissue organization and function, how this relationship may change over the lifespan, across the health-disease continuum, or differs between individuals.

NIH's vision for the HIVE is that it will become a long-term resource of high value to the larger biomedical community because it will hold an extensive range of data and tools for understanding the human body. To realize this vision in the rapidly changing biological and biomedical research landscape, it will be key for the HIVE to adapt to changes in datatypes and technologies, software for analysis and visualization. Additionally, a rapidly evolving landscape of related programs and investigator-initiated projects will challenge the HIVE in building a cohesive community. To address these challenges, the HIVE will be funded initially for four years using Other Transaction Authority (OTA) that allows the nimble addition or subtraction of specific needed expertise, tools, technologies and partnerships to realize this vision and proactively adapt to the changing landscape. It also facilitates development of close working relationships with non-traditional participants in NIH research, national and international partners pursuing similar goals, to shape an integrated collaboratory in a time-critical and sustainable manner. If successful, a separate competitive funding opportunity announcement is planned in FY22 to support the HIVE during the production phase of the program.

Challenges

As described in more detail below, the HIVE will be composed of four distinct components: (1) a Collaboration Component; (2) an Infrastructure Component; (3) a Mapping Component; and (4) a Tools Component. An application to this FOA will address only one of these components, though a coordinated set of applications to more than one component is acceptable and encouraged when pre-existing collaborations and synergies exist. There are many significant scientific, engineering, technical, and sociological challenges that are essential for these components of the HIVE to overcome together. These include but are not limited to:

developing cooperation, collaboration, trust and accountability among the Consortium members;

building a framework for cooperation and collaboration with the wider research community engaged in overlapping goals by taking advantage of existing tools and standards as appropriate;

emphasizing open science including open source;

bringing a "cloud-first" mentality which in practice means at a minimum bringing compute to the data;

creating an extensible, sustainable resource that could support 3D mapping of billions of cells within their tissue context across the whole human body;

implementing multiple pathways for users to submit, access, query and visualize data and metadata using web interfaces, API-based connections and user-developed analytical pipelines etc.

Data Accessibility

Working together, the four Components of the HIVE will have four main data accessibility responsibilities: (1) flexible management, archiving, and accessibility of diverse biomedical data types generated by the HuBMAP Consortium and later by other programs and the wider research community; (2) making HuBMAP data open, findable, accessible, interoperable, and reusable; (3) ensuring interoperability through use of existing standards, approaches, ontologies where possible; 4) addressing all relevant human data privacy concerns.

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.

Although the specific data types are unknown at time of application, the HIVE will be expected to house a diverse range of imaging and omics datasets and software tools from the Consortium with different shelf-lives and accessibility. For example, in addition to production datasets that will be used to build map releases, the should plan to host and work with other datasets including but not limited to cross-comparisons between data generated at different Tissue Mapping Centers, using mixed datasets to build QA/QC metrics, and constructing datasets for competitions to engage the external community in developing improved algorithms and analytical software. A critical area of responsibility for the HIVE is to lead development of a framework that would successfully orient and spatially position data with respect to a suitably defined common coordinate frame. Innovative solutions for integrating data across the human body with broad community agreement will be crucial to achieving the overall vision of the HuBMAP. Applicants are strongly encouraged to include plans to analysis, design, development, testing and updating of products and services of the HIVE using iterative techniques with significant end-user input.

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 encouraged to use modular and scalable solutions where information and data exchange 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 demonstrate that their approach is open and modular in nature and will not create undue burdens on the other Components of 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 like geospatial mapping, geographic information systems, astronomy, etc. that have tackled similar mapping challenges. It is important for the applicant to clarify and scientifically justify the software engineering principles they intend to adopt in developing their solutions. This includes issues of refactoring, when/where, approach towards duplication versus abstraction, approach towards agile methods such as extreme programming or Scrum or Agile Unified Process.

To the extent that information considered for inclusion in the HIVE, either as separate datasets or in combination with other data, triggers human subjects, privacy, or other laws or regulations, the HIVE must establish appropriate data sharing policies and data access procedures consistent with achieving the goals of the program, and take other steps to protect the information of research participants. In addition, if the HIVE will store and permit controlled access to genomic data, included datasets must be consistent with the NIH Genomic Data Sharing Policy (NOT-OD-14-124) and the NIH Notice for Use of Cloud Computing Services for Storage and Analysis of Controlled-Access Data Subject to the NIH Genomic Data Sharing Policy (NOT-OD-15-086), as applicable. Finally, the HIVE will be primarily responsible for developing, getting approval, and implementing any Consortium-level data sharing policies.

Data Security

Data security encompasses confidentiality, data integrity, and availability. All three elements are important for the HuBMAP and HIVE, 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 HIVE 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 (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 the HIVE Project Manager, and managing, and mediating any loss of data or compromise of data confidentiality. The HIVE 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 strongly 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, any proposed solutions using a commercial cloud are strongly encouraged to have an understanding of FedRAMP requirements (http://www.fedramp.gov) and describe an approach for building a security assessment framework.

Coordination and Collaboration

As well as being part of the HIVE, successful applicants will also become members of the larger HuBMAP Consortium composed of all investigators funded in response to HuBMAP FOAs and others who are invited to join the Consortium. The purpose of the Consortium is to enable groups to effectively collaborate with each other to maximize the chances of overall program success. Successful applicants will be expected to work collaboratively with other members of the Consortium in many activities including contributing to developing SOPs, data and metadata standards, developing metrics for data generation, participating in cross-site studies, engaging in cross-training, and guiding development of data analysis and visualization tools that can be used by the broader scientific community. All HuBMAP principal investigators, or their designates, will be required to attend the initial Kickoff meeting, planned for the fall of 2018, as well as annual HuBMAP investigator meetings, regular teleconferences with HuBMAP Network members and meetings with NIH Staff for the duration of the funding cycle. To this end, all applicants are expected to budget and commit resources to Consortium activities.

The formation of a partnership amongst all HuBMAP awardees and NIH staff is a key aspect of this program. A Steering Committee (SC) composed of all the funded principal investigators and key NIH staff will develop and implement Consortium policies, including data and metadata standards for production data, data sharing and publication policies consistent with achieving the goals of the program, 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 (EC) and a set of working groups. NIH staff will also recruit outside experts (non-awardees) to provide advice directly to NIH. Additional details of the program management are given below.

The HIVE is expected to work closely with the Tissue Mapping Centers (TMCs), who as the domain experts will have primary responsibility on how to analyze and interpret data for their specific tissues, while the HIVE will be responsible for integrating data and metadata from all the Centers into a common framework, developing tools for analyzing multiple tissues, and building tissue maps. The HIVE can expect the TMCs to generate a wide range of datasets, from raw reads and microscopy images to biospecimen metadata, as well as types of data from cross-validation to production. It should also expect the TMCs to submit annotated tissue maps that the HIVE will then integrate into a human body atlas. The HIVE is also expected to work closely with the technology development projects to understand and develop solutions for incorporating data from emerging technologies, and provide a framework for handling test, calibration and validation data in addition to production data, recognizing that access and retention will vary. It is anticipated 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. Later in the program, the HIVE will work closely with the data mining and demonstration projects to demonstrate, establish, and enhance the value of the resources developed by the program to study inter-individual variations and tissue changes across the lifespan and the health-disease continuum and other biomedical challenges faced by the larger community.

The HIVE will also lead coordination and collaboration with other related NIH programs, other international initiatives and the wider research community. The HIVE is expected to engage and build partnerships with national and international programs and researchers to keep the work of the Center relevant to the wider research community and to make sure the data and resources generated by the program are harmonized and shared in interoperable formats. The Coordinate Component is particular is charged with finding and implementing solutions to encourage and incentivize the wider research community to work with the Consortium to harmonize approaches, improve reproducibility and avoid duplication. Later in the program, the HIVE will also establish processes for accepting data generated by related programs and the wider research community. Given the complexity of the HIVE and HuBMAP, NIH is looking for innovative approaches to simplify and enable solving the human and social challenges that inevitably arise in large scientific projects.

Sustainability

As described above, NIH's vision for the HIVE is that it will become a long-term resource of high value to the larger biomedical community. It is therefore likely that the HIVE will participate and contribute to the establishment of a federated ecosystem with similar programs. The FAIR principles will be important to adopt, follow, and contribute towards their evolution. During the lifetime of the HuBMAP new scientific and technological advances are likely to happen in storing, access, and computing on data. The HIVE should aim to identify, evaluate and incorporate new data science approaches and information technologies that improve the usage, quality, and cost effectiveness of the resource. Examples include, but are not limited to, the optimization of analysis tools and workflows for cloud platforms, the adoption of new data compression methods to reduce storage costs, advances in mapping and spatial statistics approaches, tools to improve data security and protection of research participant data, and the development of tools for the parallel deployment of analysis workflows on in a federated ecosystem.

Flexibility

HuBMAP is seeking to integrate data from spatial and omics assays across a diverse range of biomolecular species including RNA, DNA, and proteins as well as extracellular features. However, at the time of application, details concerning the specific assays, choice of tissue, datatypes will not be available; it is therefore important that applicants for the HIVE FOA describe how they will exhibit nimbleness and flexibility with respect to these issues including the ability to identify and bring in specific domain expertise based upon evolving needs of the program. This may include using existing datasets from other sources such as studies with model organism systems or developing synthetic datasets to test and validate features of the platform as it is developed, or engaging consultants from industry, standards organizations or other programs to develop required features and ensure interoperability.

Although the HIVE awardees will have submitted compelling ideas in their proposal they must be prepared to adjust, add, or delete items from their proposed plan of action to align with the HuBMAP goals and action plan. Applicants should clearly articulate high priority use cases and minimally viable product(s) for the setup phase of the program for each Component. These use cases and minimally viable products, if suitably designed, will also help avoid over-engineering mistakes, overly generalized solutions (or overly abstract software engineering solutions) among other pitfalls. It is expected that awardees will need to revise and update these use cases and minimal viable products based on outreach with the larger biomedical community and feedback from NIH Staff and Program Consultants.

Scope of an Application

To respond appropriately to this opportunity announcement, applications must target one of the four Components of the HIVE listed below. A collaborative set of applications can be submitted, with the same Vision section included in each application; however, each proposed component will be reviewed separately based on objective review criteria detailed below. It is important to note different Components need different degrees of innovative solutions, different expertise, and will be managed separately with different budget envelopes, though the four Components of the HIVE will be expected to work as the seamless backbone of the HuBMAP program. It is essential that each Component should describe the principles that will be used in its varied interactions with the other Components, with the HuBMAP and with the larger biomedical community (as appropriate). Collaborative applications that establish an overarching structure to coordinate multiple functions and multiple Components are encouraged, although this is not a requirement. Collaborative applications can have the same PD/PI or the same group of multi-PIs (with same or different contact PIs). Collaborative applicants should be cognizant however that only a subset of proposed Components may be funded.

The four Components compromising the HIVE will require distinct experience and expertise, but will function seamlessly together:

• Collaboration Component (CC) the CC will be responsible for coordination and collaboration with the other funded components of the HuBMAP Consortium and the wider research community;
• Infrastructure Component (IC) the IC will be responsible for building and optimizing the data ingestion and archiving platform and support the internal and external facing IT tools for the Consortium;
• Mapping Component (MC) - the MC will be responsible for building and optimizing the framework for integrating TMC-generated tissue maps together in the context of the human body;
• Tools Component (TC) the TC will be responsible for developing search, analysis and visualization tools for HuBMAP data or enable adoption and usage of relevant ones from the community as well as serving data to computational scientists.

An application may propose only one component. However, a coordinated set of separate applications, each describing a separate component but with a common vision, can be proposed. Collaborative applications can have the same PD/PI or the same group of multi-PIs (with same or different contact PIs). It is expected that all four funded Components will function as one seamless, integrated collaboratory with tools, technologies and solutions developed by one Component to be used by others and deployed through infrastructure developed by still another Component. More specific and detailed information about each Component is described below in this section and in Section IV.

It is critical to consider the development of the HIVE in multiple stages. During the setup phase of HuBMAP (FY18), the HIVE will focus on developing and implementing the principles of data sharing, data and metadata standards including provenance (using relevant ontologies as needed and appropriate); software infrastructure for ingesting and archiving data and laying out specifications for a common coordinate system (to be developed in conjunction with the TMC and the community as needed) that can robustly support integration within an atlas of tissue maps; and developing a framework for collaborations within the entire HuBMAP. It is essential also to reach out to the broader research community through workshops especially for the Mapping and Tools Components in preparation for activities and establishing priorities for the future. Finally, during the setup phase, the awardees of the different Components are expected to agree to modalities of working that enable them to be the seamless backbone of the HuBMAP program. During the scale-up phase (FY19-FY21) of the program, the HIVE will also focus on developing and implementing data lineage and quality management tools, building mapping pipelines, search and visualization tools and increasing accessibility to the data by the broad research community. During the production phase of the program (FY22-24), currently, not part of this FOA, the HIVE will expand its focus to include developing pathways for individual investigators and other programs to submit relevant datasets, build their own analytical pipelines, and implementing other relevant analytical approaches. If the setup and scale-up phases are successful, a separate competitive FOA will be issued for the production phase.

The major activities and goals for each of the components of the HIVE are described below. It is likely that the components will be in different geographical areas and in some cases, there may be more than one award to address the goals of that component. It is also expected that interfacing between components will be refined after awards are made. Thus, it is important for each applicant to demonstrate an understanding of the organization and responsibilities of the HIVE and HuBMAP's overall goals, as well as propose methods for promoting integration of the Components to form an integrated collaboratory.

Collaboration Component (CC)

The goal for this component is to enhance the collaborations and exchange of information among Consortium members and between HuBMAP and the wider research community. It is expected that applicants to this Component will need to use the resources built by the other Components to achieve its goals. However, a CC application should propose a complete solution for its needs and adjustments will be made during OT2 negotiations prior to award. The CC is strongly encouraged to describe how it will nimbly integrate ideas and expertise from multiple disciplines to proactively adapt to the rapidly changing landscape and how it will actively manage activities to quickly solve problems and determine the best course of action by adroitly adding or subtracting projects and personnel effort.

The CC is primarily responsible for the following tasks: (1) coordination and collaboration activities within the HuBMAP Consortium and maintaining the infrastructure to make the Consortium run smoothly; (e.g. Wiki, website, calendar, dashboard etc.) (2) coordinating developing, implementation and tracking compliance with relevant operating principles, data and metadata standards for the program in collaboration with the wider research community; (3) organizing and facilitating Consortium meetings including working group and annual investigator meetings; (4) engaging with the related programs and the global research community to build the framework, datasets and tools for mapping the human body; (5) facilitating cross-fertilization within the Consortium through supporting cross-training, pilot projects, workshops, training sessions and jamborees; and (6) managing the HIVE's identify and presence, including disseminating the work and details of resources through multiple channels including outreach at meetings, a web portal, press releases and social media and regularly reporting on Consortium-wide performance and activities. Applicants should describe in detail how their approach, tools and solutions will significantly enhance exchange of information to other entities within the HuBMAP initiative and the larger biomedical community referencing previous experience.

The Collaboration Component is expected to propose specific goals and milestones for these tasks and to clearly articulate deliverables on a timeline that may address the following desired outcomes:

• nimbly engaging and building partnerships with national and international researchers to keep the work of the HIVE relevant to the wider research community against a backdrop of rapidly changing technologies, data standards and formats;
• leading development and implementation of an engagement plan that applies social science and business principles to build a collaborative community and maximize participation;
• managing working groups, interactions and documents associated with the Consortium to maximize engagement, accessibility and re-use;
• developing and implementing tools, such as a Consortium dashboard that enable the Consortium members and later the wider research community to easily keep track of datasets submitted to HIVE and biospecimens available from the Tissue Core; this includes tracking and making available datasets associated with publications, and tracking re-use of datasets;
• coordinating discussion, harmonization and adoption of relevant data standards within the Consortium and with the other related programs and the wider research community;
• coordinating discussion, harmonization and adoption of relevant metadata (using appropriate existing ontologies and controlled vocabularies where possible);
• tracking the content and access to a Consortium website, data portal and wiki, including an Consortium member-only section, details of SOPs developed by the Consortium, Consortium policies, points of contact, and details of collaborations;
• building and growing a user community for the HIVE's resources by soliciting and responding to user feedback on design and usability, monitoring usage of tools and regularly re-assessing designs;
• finding and implementing solutions to encourage and incentivize the wider research community, including both individual investigators as well as coordinated programs, to deposit and analyze data and use HIVE resources;
• organizing Consortium meetings and workshops, including the annual investigator meeting and meetings with other programs or communities;
• conducting outreach and engagement on behalf of the Consortium, including engaging non-traditional communities who are tackling related challenges, such as geographical informaticists and astronomers;
• coordinating plans for accepting data submitted from related programs and the wider research community during the second half of the scale-up phase of the program;
• building and reporting on a set of metrics that will be used to measure success of the HIVE and its activities, including community engagement, tool use and data re-use.

Infrastructure Component (IC)

The goal for this component is to establish, optimize and scale a reliable, accessible infrastructure for archiving and analysis of data generated initially by HuBMAP and later by the wider research community. It is expected that applicants to this Component will use the resources built by the other Components (as needed) to achieve its goals. However, the applicant should propose a complete solution for its needs and adjustments will be made during OT2 negotiations prior to award. The IC is strongly encouraged to describe how it nimbly integrate ideas and expertise from multiple disciplines to proactively adapt to the rapidly changing landscape and how it will actively manage activities to quickly solve problems and determine the best course of action by adroitly adding or subtracting projects and personnel effort.

The IC is primarily responsible for the following tasks: (1) establishing the pipeline for ingesting, archiving and exposing the data generated by the TMCs in a controlled, monitored fashion; (2) building and maintaining this scalable, modular data infrastructure so that it will support multiple analytical pipelines and tools for accessing and visualizing data; and (3) providing the infrastructure to support the tools and services developed by the other Components (including avoiding duplication of storage requirements and other efficiencies) once these are developed and ready for use by multiple groups within the Consortium and by the wider research community.

In collaboration with the CC and the TC, the IC will lead establishment of a process for requesting data access, and maintaining a user authentication system to allow secure access to the data and computing services of the HIVE by individual researchers and groups of users with different access privileges. The user authentication system developed for the HIVE should also be interoperable with established NIH authentication systems, such as the eRA Commons, for approved users of NIH data resources. Also, current NIH processes that authorize access to controlled access data through the NIH Data Access Committees should be supported. The IC in collaboration with the other components is also expected to develop and implement streamlined technical and administrative processes to review and authorize controlled-access data requests, while considering the data use limitations of the studies hosted by the HIVE. In addition, guidelines for the download of data from the HIVE, including data derived from computational analyses of HUBMAP datasets performed by the users, should be developed and implemented to address any privacy concerns associated with the download of individual level data. These activities will be refined in consultation with NIH HUBMAP staff and Program Consultants when the Consortium is established.

The Infrastructure Component is expected to propose specific goals and milestones for these tasks and to clearly articulate deliverables on a timeline that may address the following desired outcomes:

• providing relevant and nimble storage and computational needs for activities within the HuBMAP that is scalable based on the needs of the Consortium;
• building an ingestion portal for Consortium members to deposit different types of data (e.g. from different imaging and omics assays) for different purposes (e.g. cross-validation, calibration or production), that is user-friendly and tracks quantity and quality of data submitted;
• working closely with the TMCs on the submission and quality control of data submitted for archiving and analysis, including the development and implementation of quality metrics, collecting and integrating experimental and data handling parameters pre-submission;
• working with the CC to establish interoperability with data generated by related programs, and to plan and implement a strategy for accepting data generated from these programs or the wider research community in the second half of the scale-up phase of the program;
• implementing, testing and regularly reporting on access control, monitoring and policy compliance for data stored in archive, including infrastructure to segregate and isolate personally identifiable information or identifiable populations and assuring security and privacy;
• acting as a seamless bridge for the other Components of the HIVE and the Consortium to exchange data, deploy tools and resources for the Consortium, track progress and collaborate;
• in collaboration with the MC building and supporting a modular and scalable infrastructure that can support multiple, standardized, analytical pipelines and to display maps in the context of a common coordinate framework;
• working with the TC to develop user personas and consequently different methods for accessing, visualizing and searching the archive to enhance data analysis and re-use;
• in collaboration with the TMCs and TC developing data quality management tools, that for example can determine missing, incomplete and erroneous data, and sources of technical noise as well as developing statistical and other measures to annotate or correct this data;
• developing and standardizing pipelines (including any software engineering needed for the community to use) and working closely with the TC to maintain open, FAIR and citable principles; the IC should plan for the production phase of the program when there will be extensive data submission and community submitted data and designed data analysis pipelines;
• developing and demonstrating the capability to handle both raw and processed data as needed to address scientific questions at multiple levels of detail working in close collaboration with the Tissue Mapping Centers and the other Components;
• assessing and regularly reporting on data quantity and quality in the archive.

Mapping Component (MC)

The purpose of this component is to develop the framework for mapping the data in the archive in the context of the human body. This component will work closely with the TMCs to develop and implement a common coordinate framework and to build a resource analogous to Google Maps for the human body, which can rapidly serve the spatial, multi-dimensional data in the archive as multiple map layers that are amenable to model development. It is expected that applicants to this Component will use the resources built by the other Components (as needed) to achieve its goals. However, the applicant should propose a complete solution for its needs and adjustments will be made during OT2 negotiations prior to award. The MC is strongly encouraged to describe how it nimbly integrate ideas and expertise from multiple disciplines to proactively adapt to the rapidly changing landscape and how it will actively manage activities to quickly solve problems and determine the best course of action by adroitly adding or subtracting projects and personnel effort.

The MC is primarily responsible for the following tasks: (1) realizing a common coordinate framework for integrating data across the human body (the common coordinate framework would need to be developed in conjunction with the HuBMAP and the larger biomedical community); (2) developing and optimizing pipelines for generating tissue maps in multiple projections and non-cartesian representations; (3) managing Consortium data releases; (4) building and maintaining a user-interface for the map releases; and (5) developing and creating datasets from the archive that can be used by computational scientists to build models that will lead to better understanding of tissue organization. Applicants should describe in detail their approach for establishing a common coordinate framework and generating different types of maps that are composed of multiple annotated interactive layers, akin to a Geographic Information System-type user interface for the human body. If successful, these maps are expected to enable and encourage future studies and new insights into inter-individual variation, tissue changes across the lifespan of the health/disease continuum and for tissue engineering.

The Mapping Component is expected to propose specific goals and milestones for these tasks and to clearly articulate deliverables on a timeline that may address the following desired outcomes:

• closely coordinating with the TMCs and the rest of the Consortium to develop and implement a common coordinate framework that will track biospecimen location and orientation from collection through analysis so that data from multiple assays and samples can be integrated into a unified multi-scale, multi-dimensional atlas of the human body;
• organizing community workshops (as relevant) to solicit insights on high priority tools that build relevant tissue maps for the tissues being handled by the HUBMAP including ideas and approaches to extend them to other tissues;
• in collaboration with the IC building and supporting a modular and scalable infrastructure that can support multiple, standardized, analytical pipelines and to display maps in the context of a common coordinate framework;
• identifying data layers and types of maps needed by the research community through a needs assessment or similar; these maps may include reference maps for well-defined tissue microenvironments, genetic variant maps, pseudo-space maps organized with reference to the vasculature, or changes in biomolecular distribution associated with functional or developmental transitions
• building an object-based spatial databases map server on top of the archive layer for access and interaction with Consortium data releases; Consortium data releases will integrate Consortium datasets in the context of the human body, and include annotated features using commonly-used ontologies, associated metadata, links to underlying datasets, and details of algorithms, filtering and assumptions used;
• developing derivative datasets from the archive that enhance the ability of computational researchers to better understand intra-individual and inter-individual variation, changes across the lifespan or transitions in tissue organization; this may include developing methods for registering specimens based on anatomical landmarks, correlating expression profiles, or automated identification of microenvironments or neighborhoods;
• tracking and reporting use of the data and tools generated by the MC.

Tools Component (TC)

The goal for this component is to develop tools for enhancing findability, accessibility, interoperability, reproducibility and re-use of HuBMAP data. This component, builds on the IC to act as the primary vehicle for multiple classes of users to access HuBMAP data, by providing query and analysis capability to internal and external researchers with different levels of interest and capability. It is expected that applicants to this Component will use the resources built by the other Components (as needed) to achieve its goals. However, the applicant should propose a complete solution for its needs and adjustments will be made during OT2 negotiations prior to award. The TC is strongly encouraged to describe how it nimbly integrate ideas and expertise from multiple disciplines to proactively adapt to the rapidly changing landscape and how it will actively manage activities to quickly solve problems and determine the best course of action by adroitly adding or subtracting projects and personnel effort.

The TC is primarily responsible for the following tasks: (1) ensuring that open, FAIR, and citable guiding principles are adhered to by the Consortium; (2) enhancing the reproducibility and reliability of data that is generated and released; (3) engaging with the wider research community to develop new tools for accessing, searching and visualizing HuBMAP data; (4) providing different forms of access by packaging data and software appropriately to utilize cloud resources; and (5) coordinating implementation of metadata and data annotation across the Consortium. NIH is likely to prioritize approaches that are cloud agnostic (public vs. private; and among different commercial providers). Applicants should describe in detail how their tools will enhance FAIRness and re-use of HuBMAP data to achieve these and related goals of the HUBMAP.

The Tools Component is expected to propose specific goals and milestones for these tasks and to clearly articulate deliverables on a timeline that may address the following desired outcomes:

• organizing any relevant community workshops to establish priorities for tools and activities of this component;
• ensuring that open, FAIR, and citable principles for data and digital object management are realized;
• in collaboration with the TMCs and IC developing data quality management tools, that for example can determine missing, incomplete and erroneous data, and sources of technical noise as well as developing statistical and other measures to annotate or correct this data;
• working with the TMCs and the rest of the Consortium, leading the development and implementation of metadata standards, data segmentation and annotation, and associated ontologies and algorithms;
• working with the IC to develop user personas and consequently different methods for accessing, visualizing and searching the archive to enhance data analysis and re-use;
• building open, standardized, secure and documented APIs that support federated, intelligent searching, data monitoring and correction, and data retrieval;
• developing user interfaces (UI) primarily focused on the command line environment for various categories of researchers focused on computational aspects including access to cloud-enabled computations, APIs and access to metadata;
• deploying tools and UIs built by other components for use by the research community;
• developing cloud-based tools for statistical, machine learning, visualization and analysis of tissue maps to enable the larger biomedical community to develop new use cases for the data
• build effective ways to improve reproducibility of the results from different analytical activities undertaken within HuBMAP with a view of making any tools developed available to the wider community
• tracking and reporting use of the data and tools generated by the TC.

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. A Technical Assistance teleconference will be held for potential applicants. 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). 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 Other Transaction Award Policy Guide for the HuBMAP Program will apply to the applications submitted and awards made from this FOA.

Higher Education Institutions

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

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

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government
• 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)
• Federally Funded Research and Development Centers (FFRDC) and University Affiliated Research Centers (UARC)

FFRDCs and UARCs are eligible to apply and/or participate as partnering organizations. NIH will not award funds specifically for laboratory directed research and development (LDRD) costs. Laboratory contractors may recover LDRD costs within the total funding included in the award. Other costs will be reviewed and negotiated prior to award.

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 NIH Other Transaction Award Policy Guide for the HuBMAP Program 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.

This FOA does not require cost sharing as defined in the NIH Other Transaction Award Policy Guide for the HuBMAP Program. Applicants may voluntarily choose to propose a financial plan that includes non-federal resources. The OT2 budget submission must clearly identify and justify the use of these resources. Any voluntary cost share must be supported by a letter of support from the providing organizations/individual. All voluntary cost share provided is also required to adhere to the HuBMAP OT Award Policy Guide.

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

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed in this funding opportunity announcement to do otherwise. 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.

Required Letter of Intent Instructions

By February 28, 2018, prospective applicants are required to submit a Letter of Intent for each Component. Applications will not be accepted for review, unless a Letter of Intent has been submitted, accepted, and a formal invitation to apply from NIH has been issued. The Letter of Intent should include the following information:

• Number and title of this funding opportunity.
• Descriptive title of proposed activity. For a LOI covering multiple, coordinated component applications, please submit separate information for each component, use the same title for all components and denote "[M of N]" (e.g., 1 of 3) in the title. Please also clearly indicate for each component any overlap in personnel.
• Table of Principal Investigator(s), Key Personnel, and Co-Investigators, and their respective Roles and Institutional Affiliations.
• International applicant or international subawards. YES/NO. If YES, please provide details of foreign PIs and institutions involved.
• Human Subjects. YES/NO.
• Clinical Trial. YES/NO.
• Vertebrate Animals. YES/NO
• Overview and strategy (2 pages maximum). Common descriptions can be used for coordinated applications.
• Clearly identify the Component the applicant will be requesting funding for.
• Provide an overview of the proposed effort and describe how these will contribute to achieving the goals of the HuBMAP and the HIVE.
• Describe the research strategy you will pursue to realize the goals of the Component and the HIVE.
• List deliverables and milestones for the first year of the program and give an overview of major goals and milestones beyond the first year.
• Give examples of projects you have been instrumental in developing that is relevant to the Component you are applying while describing how you overcame specific challenges in past work. Clearly describe how the challenges you faced in prior work overlap with the Component you are applying to.
• Please describe your experience in working in large complex programs, complex software engineering and sociological situations.
• Please describe the scientific, software engineering, and sociological principles that you will follow in establishing interactions and effective working relationship to develop a seamless HIVE between your Component and the other Components.
• Describe any collaborative linkages being developed between the project and other NIH funded projects.
• Personnel qualifications: (1 pages maximum). Please indicate personnel involved in coordinated applications.
• Description of relevant expertise for all key personnel, not to exceed 100 words per person
• Describe your experience in milestone driven projects.
• Describe your experience in contributing towards enabling overall goals of a larger effort.
• Describe your software development philosophy and approaches that you have used in past projects that would be useful in this effort.
• Estimated budget for the first year.
• Provide up to 3 letters of support, as appropriate. Include any letters of support for the proposed project by appropriate institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the project and its goals. Do not provide letters of support from individuals who will not be involved in the project's research activities.

Letters of Intent will be evaluated by NIH Program Staff based on the scientific and technical merit of the proposed project, including: (1) the relevance of the proposed research to the HIVE and the HuBMAP, (2) the expertise, commitment and track-record of the project team, (3) whether the vision and benchmarks, deliverables, timeline, and budget are congruent with the tasks of that component and (4) whether the proposed work will realistically deliver the required capabilities as part of an actively managed Other Transaction. Collaborative applicants should be cognizant however that only a subset of proposed Components may be invited to submit a full application. Teams which submit Letters of Intent by February 28, 2018 will be notified by March 9, 2018 if they are invited to submit a full application.

Letters of intent should be submitted by email to:

Ajay Pillai, Ph.D.
Telephone: 301-496-7531
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed. The page limit for the Research Strategy is 12 pages.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

Cover Letter Attachment: A copy of the Invitation to Submit must be included in the Cover Letter attachment on the Cover form to demonstrate NIH concurrence with this submission in response to a successful Letter of Intent (LOI). The Cover Letter attachment should be addressed to the Division of Receipt and Referral.

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

All instructions in the SF424 (R&R) Application Guide must be followed. The project information should include:

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

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

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

Overall: Provide the overall total costs for the four years for each of the following categories: personnel, equipment, travel, subawards, other direct costs, and total cost (with indirect costs included). Provide a budget justification for all years of the project. Indirect costs for domestic awards will be reimbursed using the applicant's federal negotiated indirect cost rate. Consistent with 45 CFR 75.414(f), any institution of higher education (IHE), nonprofit organization, or state or local government that has never received a negotiated indirect cost rate, may elect to charge a de minimis rate of 10% of modified total direct costs (MTDC) which may be used indefinitely. Indirect costs on foreign awards will be reimbursed at a rate of 8% of total direct costs, less only equipment.

Personnel: The PD/PI of an individual Component must devote a minimum of 2 person-months of effort. For a multi-PI application, the effort for each PI must exceed 1.2 person-months of effort. For collaborative applications with the same PD/PI on multiple components, the PD/PI effort must exceed 1.2 person-months of effort per Component.

Equipment: If pieces of specialized equipment or computers exceeding $5,000 are requested, the application must provide a clear justification for the purchase in Budget Justification.

Travel: Applicants need to budget for attending bi-annual meetings of the HuBMAP Consortium (these meetings are expected to be held in Bethesda, Maryland). Additionally, applicants need to budget for travel to other consortium sites for information exchange and international activities. HIVE Components are encouraged to plan to send personnel to the Tissue Mapping Centers for extended visits to enable effective communication, development of tools and solutions that would enable the Component to create the most effective solutions for realizing the overall goals of the HuBMAP.

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.

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

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

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

Research Strategy

On the Research Strategy attachment, please use the sub-sections defined below:

Vision and Overview

This section should provide an overview of the component and the vision for how the component will work as part of the HIVE and the HuBMAP Consortium. Do not consider this to be a traditional Specific Aims page for hypothesis-driven research. Briefly state the goals of the component and how the deliverables address the aims and goals of this FOA. Provide a summary of major tasks to be accomplished with milestones and benchmarks, a timeline, and deliverables. In addition, the following elements should be specifically addressed:

• Title for the HIVE Component; for multiple, coordinated component applications, please use the same title for all components and denote "[M of N]" (e.g., 1 of 3) in the title. Please also clearly indicate for each component if the same PD/PI or multi-PI groups are involved. The vision for a coordinated set of applications should be the same for each Component application;
• The applicant's vision for how the proposed work fits in within the overall scope of the HIVE and the HuBMAP program as described in this FOA including the long-term vision for the HIVE beyond the duration of HUBMAP;
• A plan for how the applicant proposes to work with NIH staff and other components of the HIVE to create an integrated collaboratory;
• Qualifications, past performance and experience of the key personnel, particularly working on actively managed, milestone-driven projects;
• It is essential that the applicant demonstrates flexibility to adapt to the changing needs of this complex project especially given the larger world-wide scientific context of multiple projects that are ongoing while remaining true to the broad vision for the HuBMAP program;
• Outreach and collaboration within and outside of HuBMAP are critical aspects of a successful HIVE and the applicant needs to describe the processes and procedure they will adopt to enhance the utility, usability, and acceptability of their solutions by the broader community;
• Specify a framework for how the interactions and handover between the different components should best be handled and how your proposal would fit into such a framework;
• Details of any cost-sharing, institutional commitment or existing infrastructure or collaborations that the component is building off.

Scientific, Technical and Management Strategy

Do not consider this to be a traditional Research Strategy. The objective of this FOA is to identify projects and teams who can develop the data infrastructure and collaborative community needed by the HuBMAP Consortium and the broader research community as described above. This section should be structured to provide sufficient information to gauge the applicant's likelihood of producing the deliverables and achieving their objectives. This section should cover the following aspects:

• Impact and Significance: Identify the HIVE Component being addressed in this application. Briefly describe the key features of this application and highlight any conceptual, technical, and/or methodological innovations that increase the significance of the proposed project. Compare your approach to existing state-of-the-art approaches.
• Preliminary Data: Provide a description of any prior work that is of significance to the proposal. Describe the Preliminary Data, if available. Preliminary data is not required for a successful application.
• Development Plan: Describe in detail the specific tasks of relevance and importance to realizing the goals and vision for the Component, the HIVE, and HuBMAP (as appropriate). The plan should demonstrate deep understanding of the technical, scientific and sociological challenges and present a credible plan to achieve the goals.
• Validation Plan: Describe relevant use cases and minimal viable product that is being proposed including plans to adjust (if needed) based on feedback from the HuBMAP or the larger community. Describe how the tasks identified fit into these use cases or minimal viable products.
• Risk Analysis: Provide a description of potential pitfalls and limitations, and approaches to mitigate them.
• Tasks, benchmarks, timeline: For each major task, describe the expected outcomes and deliverables. Include benchmarks for each task that can be used to evaluate interim and final progress towards the deliverables. Benchmarks should include quantifiable criteria for success (i.e. go/no-go), and should aggressively address major risks in the first year of the project. The criteria for success and benchmarks should be based on quantitative estimates, if possible. The timeline must include benchmarks, deliverables, and release of specific infrastructure or other tools. A Gantt chart or similar approach is strongly encouraged.
• Interactions with Other Components: Describe clearly what you will enable so that all Components can utilize your products and solutions as needed in order to create a seamless HIVE. These should include scientific, software engineering and sociological challenges.
• Investigators: Describe past collaborations between the key personnel, if any. Responsibility for interfacing with the HuBMAP Tissue Mapping Centers and other Components of the HIVE must explicitly be assigned to one or more individual(s) planned contributions.
• Project Management: Describe the leadership and management plan for the component. If the project is to be carried out in more than one department or institution, identify what parts of the project will take place at each organization and which senior/key individuals will be responsible for each portion.
• Privacy & Confidentiality: Data security encompasses confidentiality, data integrity, and availability. All three elements are important for the HuBMAP and HIVE, and maintaining confidentiality of controlled access data is a particularly high priority. Describe your plans to achieve these goals as pertinent, applicable, and of significance for your Component. Highlight any standards or widely accepted frameworks that you will adopt or be compliant with.
• Flexibility: It is expected that at least two technologies for gene expression (due to their maturity) will be part of the Tissue Mapping Center: RNA-Seq and FISH. However, other technologies and approaches will be included but unknown at the time of application and therefore the applicant must describe how they plan to enhance their expertise into new domains over time. Applications need to outline a plan on how feedback will be obtained to refine and adapt objectives and approaches.

Collaboration Component (CC): For the CC specifically, please describe the strategy for: (1) coordination and collaboration activities within the HuBMAP Consortium and maintaining the infrastructure to make the Consortium run smoothly; (2) coordinating developing, implementation and tracking compliance with relevant operating principles, data and metadata standards for the program in collaboration with the wider research community; (3) organizing and facilitating Consortium meetings including working group and annual investigator meetings; (4) engaging with the related programs and the global research community to build the framework, datasets and tools for mapping the human body; (5) facilitating cross-fertilization within the Consortium; and (6) managing the HIVE's identify and presence.

Infrastructure Component (IC): For the IC specifically, please describe the strategy for: (1) establishing the pipeline for ingesting, archiving and exposing the data generated by the TMCs in a controlled, monitored fashion; (2) building and maintaining this scalable, modular data infrastructure so that it will support multiple analytical pipelines and tools for accessing and visualizing data; and (3) providing the infrastructure to support the tools and services developed by the other Components.

Mapping Component (MC): For the MC specifically, please describe the strategy for: (1) realizing a common coordinate framework for integrating data across the human body; (2) developing and optimizing pipelines for generating tissue maps in multiple projections and non-cartesian representations; (3) managing Consortium data releases; (4) building and maintaining a user-interface for the map releases; and (5) developing and creating datasets from the archive that can be used by computational scientists to build models that will lead to better understanding of tissue organization.

Tools Component (TC): For the TC specifically, please describe the strategy for: (1) ensuring that open, FAIR, and citable guiding principles are adhered to by the Consortium; (2) enhancing the reproducibility and reliability of data that is generated and released; (3) engaging with the wider research community to develop new tools for accessing, searching and visualizing HuBMAP data; (4) providing different forms of access by packaging data and software appropriately to utilize cloud resources; and (5) coordinating implementation of metadata and data annotation across the Consortium.

Letters of Support

Provide any letters of support, as appropriate. Include any letters of support for the proposed project by appropriate institutional officials. Letters should address the commitment of the parent organization, or any of its partners, to the project and its goals. The parent institution is expected to recognize the project as a formal organizational component and provide documented evidence of space dedicated to the needs of the project, protected time to devote to project activities, staff recruitment, dedicated equipment, or other financial support for the proposed project. The parent institution should provide assurance of its commitment to continuing support of the project 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 project.

If collaborative linkages are being developed between the project and other local NIH funded centers in related areas a letter of agreement from the collaborating PD(s)/PI(s) should be included. Do not provide letters of support from individuals who will not be involved in the project'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 consistent with achieving the goals of the program, 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, and may include anticipated charges for Publication or data sharing and resources that may be needed to support a proposed Resource Sharing Plan in the budget plan of their application.

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:

Only limited Appendix materials are allowed. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When involving NIH-defined human subjects research, clinical research, and/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, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or 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.

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

Foreign (non-U.S.) institutions must follow policies described in the NIH Other Transaction Award Policy Guide for the HuBMAP Program, and procedures for foreign institutions.

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). 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 Other Transaction awards under HUBMAP are subject to the terms and conditions, and other considerations described in the NIH Other Transaction Award Policy Guide for the HUBMAP Program.

Pre-award costs as described in the NIH Other Transaction Award Policy Guide for the HUBMAP Program are not allowed.

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

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) 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. See Section III of this FOA for information on registration requirements.

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. 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.

Applicants are required to follow the instructions for post-submission materials, as described in NIH Other Transaction Award Policy Guide for the HUBMAP Program. Any instructions provided here are in addition to the instructions in the policy.

Only the criteria described below will be considered in the review process. For this particular announcement, reviewers will consider each of the criterion below and assign each an impact score of 1-9 (1=high score, 9 = low score). An application does not need to be strong in all categories to be judged likely to have major scientific impact. Note that innovation is not a scored criterion.

The criteria below are listed in the order of relative importance with weights assigned for evaluation purposes. The applicant shall include all information which documents and/or supports the criteria in the application.

Criterion: Merit of Scientific, Technical and Management Strategy (60% of Overall Impact)

• Will this Component make a significant contribution to the overall goals and objectives of the Human BioMolecular Atlas Program? Will the proposed work of the Component lead to be a better understanding of the relationship between tissue organization and function?
• Is there high potential for this Component to make substantial progress to achieving the goals of the HIVE? Does the Component 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 vision for the HIVE?
• To what degree do the proposed plans address the data management, map building, consortium coordination, or community engagement needs of the HIVE? To what degree do the proposed plans address major challenges in data management, consortium coordination, or community engagement?
• Is the engineering, technological and sociological approaches proposed, including demonstrated flexibility likely to lead to a viable solution for the long-term vision of the HuBMAP and HIVE?
• Are the proposed project benchmarks feasible and congruent with the goals outlined for the Component?
• Are the proposed plans, methods, techniques, and procedures for the research sound, feasible, and valid?
• Are anticipated risks and challenges associated with the approach adequately addressed? Are the proposed mitigation plans acceptable?
• Is the proposed design, technical and engagement approaches likely to lead to effective adoption of solutions, tools and products by the other components?
• Is the timeline of deliverables feasible?
• Will the proposed work be managed effectively, achieve its goals and be flexible to evolving needs as an Other Transaction award?
• For the specific HIVE Components:
• CC: Are the plans for each of the distinct activities listed in the FOA likely to lead to a Consortium that is more than the sum of its parts and engage the wider research community in building a high-quality resource for which there will be a sustained demand?
• IC: Are the plans for each of the distinct activities listed in the FOA like data deposition, QA/QC of the data, standardizing pipelines and outreach external to HuBMAP, sufficiently balanced, standardized and modular to rapidly create an effective solution that can be scaled to meet the infrastructure needs of the program?
• MC: Are the plans for each of the distinct activities listed in the FOA like a common coordinate framework, pipelines for generating tissue maps, data releases, and user-interface sufficiently balanced, innovative and responsive to community input to create an effective overall solution that will be used by the wider research community?
• TC: Are the plans for each of the distinct activities listed in the FOA like FAIR metrics, design of APIs, cloud-solutions, utility by bioinformatics and computational scientists in the community, sufficiently balanced to create an effective overall solution? Are the approaches likely to lead to effective federated solution for data repositories for storing, accessing, data of relevance to broader HuBMAP goals?

Criterion: Personnel Qualifications (30% of Overall Impact)

• Does the performance and duties of the Component Director demonstrate strong qualifications to lead the Component and match their role in the HIVE?
• Does the Component Director and key personnel have the appropriate experience in managing complex, distributed projects involving diverse teams of scientists?
• Does the Component Director and key personnel have a strong track-record of managing, integrating or analyzing multiplexed, multi-scale imaging and omics data as part of a consortium?
• Is there a clear leadership plan that will enhance the likelihood of success?
• Is the necessary expertise committed to the degree required for the research project to be successful as an Other Transaction?
• Is the potential to collaborate effectively in a multidisciplinary environment strong? For example, is there strong evidence of:
• Ability to integrate diverse sources of information;
• Experience in successful, high impact collaborations, including past leadership of collaborations;
• Commitment to executing effective strategies for accomplishing collaborative goals?

Criterion: Institutional Commitment (10% of Overall Impact)

• Is there evidence of a long-term commitment by the applicant's organization (if any) to the applicant and the research in the form of a letter of support?

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

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 project 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 project 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 (GDS).

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 by an appropriate review group convened by the Office of the Director, NIH, using the criteria described in Section V.1. by a group of NIH Program staff and outside experts. Assignment to the review group will be shown in the eRA Commons.

As part of objective review, all applications:

• Using the using the criteria described in Section V.1., those candidates identified as the most outstanding will be invited to participate in an interview in June 2018. Interviews will be conducted by a panel of distinguished outside experts. The interviews will be conducted either in-person or via videocast. NIH will not support travel for these interviews. The same review criteria described in Section V.1.will be used during the interviews.
• Will receive a review summary

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

The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by objective 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 technology development taking into consideration the needs of end users.
• Evidence that the project will contribute to the diversity of technical and intellectual approaches and to the overall goals of the HuBMAP program

PDs/PIs will be notified in early June 2018 whether or not they have been selected for an interview later that month. Interviews may be conducted in-person or via videocast. After interviews are completed, PD/PIs who were interviewed will receive a written summary of the review. Refer to Part 1 for dates for earliest start date.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Other Transaction Award Policy Guide for the HUBMAP Program.

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.

All Other Transaction awards under HuBMAP include the NIH Other Transaction Award Policy Guide for the HuBMAP Program as part of the NoA. For these terms of award, see the NIH Other Transaction Award Policy Guide for the HuBMAP Program Part II: Terms and Conditions of HuBMAP Other Transaction Awards.

The following special terms of award are in addition to, and not in lieu of, other HHS, and NIH Other Transactions administration policies.

The administrative and funding instrument used for this program will be the Other Transaction, OT2 mechanism, in which active oversight and management by the NIH is expected during the performance of the activities. Under an OT, the NIH purpose is to support and stimulate the recipients' activities by involvement in and otherwise working jointly with the award recipients. OTs offer considerable flexibility to renegotiate or terminate agreements when necessary to promote the overall objectives of the program. The award and post-award negotiations will reinforce program objectives and, if necessary, adjust conditions by which progress is assessed.

• 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.

The Principal Investigator (PI) will coordinate project activities scientifically and administratively. The PI will have primary responsibility for defining the details for the projects and for meeting the goals and milestones developed. The PI will agree to accept the close coordination, cooperation, and participation of the NIH staff (HIVE Project Scientist(s), HIVE Project Manager and Agreement Officer) in those aspects of scientific and technical management of the project as described below.

The Program Director/Principal Investigator (PD/PI) will assume responsibility and accountability to the applicant organization officials and to the NIH for the performance and proper conduct of the research supported under this Funding Opportunity Announcement in accordance with the terms and conditions of award, as well as all pertinent laws, regulations and policies (NIH Other Transaction Award Policy Guide for the HuBMAP Program). Furthermore, the Awardee(s)/PD(s)/PI(s) will:

• Work with the HIVE Project Manager to define the research objectives and approaches; plan research; conduct analyses; and publish results, interpretations, and conclusions of studies conducted under the award;
• Adhere to the project benchmarks negotiated at the time of the award, and modified as necessary, by the HIVE Project Manager and Agreement Officer to ensure progress;
• Provide, on request, updated goals and milestones for software engineering and other tasks involved in implementation, including costs as requested;
• Serve on the HuBMAP Steering Committee meetings and relevant Consortium working groups on the phone or in person;
• Assist in developing HuBMAP policies, including data release, privacy, data protection, IP, publications and other issues that will affect the success of the HuBMAP program;
• Adhere to HuBMAP policies, including those related to data release, IP, publications, and other policies that might be established, as agreed upon by the HuBMAP Steering Committee; for individual awards these policies may be superseded by negotiated terms and conditions of award;
• Ensure that all the goals of the Component are met in a manner that assists other Components of the HIVE to succeed in their goals;
• Serve on the HIVE Implementation Committee and adhere to its decisions and policies, software and engineering solutions;
• Work in a cooperative and interactive manner with NIH staff, the other HIVE Components and with the other participants in the HUBMAP Consortium to make HuBMAP data rapidly available in an open, findable, accessible, interoperable and re-useable manner;
• Adhere to the goals and function according to the process and requirements described in this Funding Opportunity Announcement and the NIH Other Transaction Award Policy Guide for the HuBMAP Program.

HIVE Project Manager

The HIVE Project Manager is an NIH extramural scientist who would have substantial involvement in assessing progress and making recommendations about future funding for the HIVE. The HIVE Project Manager may consult other NIH and non-NIH experts in making determinations.

The HIVE Project Manager will:

• Have substantial scientific programmatic involvement in the direction of the Component including in areas such as quality control, research coordination and performance monitoring;
• Coordinate, facilitate and otherwise actively manage the relationships with the HIVE Components; they may also coordinate across individual projects to combine, add to, or subtract from research being done in order to increase quality, accelerate the progress of research, realize economies, or discontinue duplicative or low-priority approaches;
• With the Agreement Officer, and appropriate supplemental personnel, the Project Manager will establish, monitor and administer each OT award on an ongoing, adaptive basis;
• Approve progress reports, and negotiate goals and milestones;
• Participate in HuBMAP Steering Committee and Executive Committee meetings as a non-voting member;
• Review all activities with input from multiple sources to ensure objectives are being met;
• Attend working meetings of HuBMAP organized activities that involve more than one awardee, as needed, to provide input;
• Assist in developing policies relating to data, experiments, priorities, that effect the entire HuBMAP program;
• Coordinate across individual projects in the HuBMAP program to combine, add to, or subtract from research being done in order to increase quality, accelerate the progress of research, realize economies, or discontinue duplicative or low-priority approaches;
• Recommend any budget changes including termination of an award to the HuBMAP Agreements Officer.

HIVE Project Scientist(s)

HIVE Project Scientist(s) are NIH extramural program scientists who will have substantial scientific involvement during the conduct of this activity, through technical assistance, advice, and coordination. To carry out their duties, Project Scientists may consult with non-NIH experts in the field.

HIVE Project Scientists will:

• Assist in developing and adapting reasonable milestones for the project with the goal of ensuring overall HIVE goals are met;
• Assist in exploring new technologies and approaches for implementing solutions;
• Assist in developing SOPs and policies for all aspects of the HIVE;
• Assist in integrating with all awardees of the HuBMAP program and other relevant non-HuBMAP activities as relevant;
• Assist in avoiding unwarranted duplication of effort;
• Assist in defining appropriate handover and other dependencies between the Components of the HIVE;
• Review and comment to progress of each Component as well as other Components of the HIVE;
• Participate in HIVE Implementation Committee meetings, the HuBMAP Steering Committee meetings and associated working groups and EPC meetings;
• Coordinate across individual Components of the HIVE to combine, add to, or subtract from research being done in order to increase quality, accelerate the progress of research, realize economies, or discontinue duplicative or low-priority approaches;
• Participate in HuBMAP Steering Committee meetings as non-voting members;
• Assist in developing HuBMAP policies on data release, IP, publications and other issues that will affect the success of HuBMAP program.

Close interaction among the Component PD/PIs will be required, as well as significant interactions with other funded projects as part of HuBMAP and NIH staff during each phase of the program. The awardees, the HIVE Project Manager and Project Scientists, 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

NIH may terminate or extend an award for convenience. For example, to advance the goals of the HUBMAP program, NIH may extend or terminate due to a change in programmatic needs or changes in the availability of funds for the project.

Records will be kept to document performance. In the case of failure to achieve benchmarks, the HUBMAP Program Manager and the Agreement Officer will make serious efforts to assist in improving the performance of a project to meet or adjust benchmarks in order to achieve programmatic goals and protect the investment. NIH generally will suspend (rather than immediately terminate) an OT award and allow the recipient an opportunity to take appropriate corrective action before NIH makes a termination decision. However, NIH may decide to terminate the award if the recipient does not take appropriate corrective action during the period of suspension. NIH may immediately terminate an award when necessary, such as to protect the public health and welfare from the effects of a serious deficiency. If the NIH decides to terminate an award, the termination of the award will be considered a unilateral change and the recipient will not have the right to appeal. Unilateral changes will be based on HIVE Project Manager, HuBMAP Program Manager and external evaluators' assessments and are subject to approval by the Director of the Division of Program, Coordination, Planning, and Strategic Initiatives. Although a decision is made to terminate an award, the recipient must continue to comply with the Record Retention and Access requirements contained in the NIH Other Transaction Award Policy Guide for the HUBMAP Program.

In addition, if NIH determines that a recipient has failed to materially comply with the terms and conditions of award, NIH may take one or more enforcement actions which include disallowing costs, withholding of further awards, or wholly or partly suspending the Other Transaction award, pending corrective action. NIH may also terminate the award for cause.

An Other Transaction award meeting or exceeding its milestones and playing a central role in meeting programmatic needs may also be extended in time with prior NIH approval. NIH staff will work with awardees to determine additional benchmarks and goals for an extension.

An Other Transaction award also may be terminated, partially or totally, by the recipient. If the recipient decides to terminate a portion of an Other Transaction award, NIH may determine that the remaining portion of the award will not accomplish the purposes for which the Other Transaction award was originally awarded. In any such case, NIH will advise the recipient of the possibility of termination of the entire Other Transaction award and allow the recipient to withdraw its termination request. If the recipient does not withdraw its request for partial termination, NIH may initiate procedures to terminate the entire award for cause.

Cooperative Agreement Terms and Conditions of Award

Not Applicable

Awardees will be required to submit a Research Progress Report at least annually and financial statements as required in the NIH Other Transaction Award Policy Guide for the HUBMAP Program.

In addition, two reports on research progress will be made per year at HUBMAP Steering Committee meetings and slides and supporting materials will be made part of the permanent record.

A Final Research Report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award as described in the NIH Other Transaction Award Policy Guide for the HUBMAP Program.

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: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573

Ajay Pillai, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-496-7531
Email: [email protected]

Jessica Smith, Ph.D.
Office of the Director (OD)
Telephone: (301) 451-3178
Email: [email protected]

Terri Jarosik
National Institute of Mental Health (NIMH)
Telephone: 301-443-3858
Email: [email protected]

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

Awards are made under the Other Transaction Authority (OTA) as authorized and appropriated by the Consolidated Appropriations Act, 2016, Division H, Title II, Sec. 215 (P.L. 114-113).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.