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 purpose of this Funding Opportunity Announcement (FOA) is to identify and support a Human Tumor Atlas Network (HTAN) Data Coordinating Center (DCC). The HTAN-DCC will have two major areas of responsibility: (1) Data Standards, Storage, Analysis, and Dissemination; and, (2) Consortium Coordination and Outreach. The HTAN-DCC will collect, store, curate, and disseminate all data, metadata, analysis and visualization tools, computational models, and completed atlases generated by the HTAN. Additionally, the DCC will lead the development of common data elements, data and metadata standards, clinical and epidemiological data requirements, and data processing pipelines. The DCC will also coordinate HTAN activities including in-person and virtual Network Steering Committee meetings and working groups. Finally, the HTAN-DCC will promote collaboration and communication among HTAN Investigators and the broader research community and coordinate the Network outreach activities.

The HTAN-DCC will be part of the Human Tumor Atlas Network (HTAN), which will also include HTA Research Centers (solicited under RFA-CA-17-034), PreCancer Atlas (PCA) Research Centers (solicited under RFA-CA-17-035) and an HTAN Tissue Coordinating Center (anticipated to be developed in Fiscal Year 2019).

NCI convened the Blue Ribbon Panel (BRP) in 2016 to provide recommendations for achieving the Cancer Moonshot's ambitious goal of making a decade's worth of progress in cancer prevention, diagnosis, and treatment in just 5 years, now called the Beau Biden Cancer MoonshotSM Initiative. The BRP was charged with assessing the state of the science in specific areas and identifying major research opportunities that could uniquely benefit from the support of the Cancer Moonshot and could lead to significant advances in our understanding of cancer and in how to intervene in its initiation and progression. The recommendations focused on areas in which a coordinated effort could profoundly accelerate the pace of progress in the fight against cancer and were not intended to replace existing cancer programs, initiatives, and policies already underway. The BRP final report was approved by the National Cancer Advisory Board and included a recommendation for the Generation of Human Tumor Atlases (BRP Recommendation I). The 21st Century Cures Act was signed into law in December 2016 dedicating new funds to support efforts associated with the Beau Biden Cancer MoonshotSM Initiative, including support for this FOA.

The goals of the HTAN are aligned with opportunities defined by the Blue Ribbon Panel (BRP) of the Beau Biden Cancer MoonshotSM Initiative. While the BRP final report includes a specific recommendation for the Generation of Human Tumor Atlases to facilitate our understanding of important transitions during the course of tumorigenesis and to inform clinical decision-making and treatment options for patients, this FOA establishes a detailed framework for the accomplishment of the BRP goals.

A major hindrance to prevention, early detection, and treatment of cancer is the lack of comprehensive knowledge of the molecular, cellular, and tissue alterations that drive tumor development and progression from its earliest stages. It is now well appreciated that the tumor ecosystem, which is defined by a full suite of cell types including tumor cells, tumor-associated immune, stroma, and vascular cells, and the accompanying patient normal and stem cell populations, evolves during tumor development and treatment. Interactions between evolving cellular and non-cellular components within the tumor ecosystem can facilitate a variety of tumor behaviors including unchecked tumor growth due to positive feedback loops mediated by tumor and stromal cell-associated secreted factors, tumor cell invasion mediated by biophysical cues arising from dysregulated extracellular matrix architectures, or positive patient outcomes, such as tumor resolution via an activated immune system. Mechanistic studies involving isolated cell populations or non-human model systems provide significant insights into the molecular underpinnings of these tumor phenotypes and have led to development of effective therapies in some contexts. However, precision medicine strategies have proven ineffective in many cancer patients due in part to an incomplete understanding of how interactions within the tumor ecosystem promote or suppress tumorigenesis.

Emerging single-cell and in situ technologies are now facilitating the multi-omic characterization of all major cell types (normal, pre-malignant, malignant, stromal, vascular, and immune) and their interactions at sites of tumor initiation, growth, and metastasis. Integration of these data with non-invasive measurements from liquid biopsy techniques and/or a variety of imaging modalities, such as multimodal molecular imaging or high-resolution optical imaging, could result in a multiparameter, multidimensional view of the evolving tumor ecosystem during cancer progression. Recognizing that a concerted, multidisciplinary effort to map human tumors could significantly accelerate scientific discovery and inform clinical decision-making, the Cancer Moonshot BRP recommended construction of dynamic tumor atlases that utilize new and existing data sets to comprehensively characterize the components and interactions within the three-dimensional tumor ecosystem over time. Ultimately, a complete set of human tumor atlases will represent the multidimensional molecular, cellular, and morphological mapping of the structure, composition and interactions within human cancers including dynamic changes that occur during key transitions in cancer, such as the progression of pre-malignant lesions toward malignancy, the initiation of invasive, metastatic disease, and the development of resistance to therapy.

Goal of the Human Tumor Atlas Network:

The NCI intends to support HTA and PCA Research Centers that will function as part of the Human Tumor Atlas Network (HTAN). The HTAN effort builds upon and extends the efforts of The Cancer Genome Atlas (TCGA) which provided genomic and transcriptomic characterization of many tumor types, resulting in an important resource for the scientific and clinical communities while promoting advances in associated technologies and bioinformatic approaches. The HTAN will focus on longitudinal studies of pre-cancer, metastasis, and drug resistance with an emphasis on collecting comprehensive clinical data over time. Furthermore, the tumor atlases generated by the HTAN will facilitate understanding of interactions within multidimensional architecture of the tumor microenvironment, including the role of the immune system, normal cells, and non-cellular components. HTAN will build upon the lessons learned from TCGA, address its limitations, and use evolving state-of-the-art information technology and other emerging technologies to achieve its goal.

The goal of the HTAN is the construction of human tumor atlases that describe the multidimensional cellular, morphological and molecular mapping of human cancers over time for informing future cancer research and, ultimately, clinical decision-making. The human tumor atlases resulting from the HTAN efforts will lend support for evidence-based expansion of the HTAN after completion of the initial 5-year pilot phase.

The HTAN will support two types of atlas-building initiatives spanning the entire continuum of cancer:

• The Human Tumor Atlas (HTA) Research Centers (RFA-CA-17-034) that will construct atlases describing the transition from locally invasive to metastatic cancer, dynamic response to therapy, and development of therapeutic resistance.
• The PreCancer Atlas (PCA) Research Centers (RFA-CA-17-035) that will construct atlases describing how and when premalignant lesions progress to invasive cancer, regress, or obtain a state of equilibrium.

The atlas-building initiatives will be supported by:

• An HTAN Data Coordinating Center (HTAN-DCC), described in this FOA, that will be responsible for data storage, harmonization, distribution, and compilation of the final human tumor atlas collection.
• An HTAN Tissue Coordinating Center (HTAN-TCC; anticipated to be developed in Fiscal Year 2019), that will provide a virtual resource for the investigators to identify and share available biospecimens across the HTAN.

Human tumor atlases developed as part of the HTAN will facilitate future research and generate hypotheses to answer important cancer questions, such as, but not limited to:

• The role of spatial and temporal interactions between tumor cells and the immune system in facilitating tumor progression, regression, or a state of equilibrium, promoting cancer metastasis, enhancing response to traditional, targeted, and/or immuno-therapy.
• Studies focused on clonal evolution, heterogeneity of pre-cancerous lesions and invasive tumors, and changes in the tumor microenvironment in space and time.
• Development of experimental and computational models to better understand the spatial and temporal molecular and cellular dynamic relationships during tumor development and progression.
• Identification of spatial, functional, and/or temporal biomarkers that predict cancer risk, targets for early intervention, and response to therapeutic intervention.
• Identification of new link(s) between molecular genetic alterations and spatial and structural alterations during tumor progression and as a result of treatment with therapeutic agents.
• Identification of spatial, functional, and/or temporal biomarkers that predict cancer risk and/or response to therapeutic intervention.

Objective of the HTAN Data Coordinating Center

The overarching mission of the HTAN-DCC will be to collect, store, curate, and disseminate all data, metadata, analysis and visualization tools, computational models, and completed atlases generated by the HTAN. Additionally, the DCC will lead the development of common data elements, data and metadata standards, clinical and epidemiological data requirements, and data processing pipelines. The DCC will also coordinate HTAN activities including in-person and virtual Network Steering Committee meetings and working groups. Finally, the HTAN-DCC will promote collaboration and communication among HTAN Investigators and the broader research community and coordinate the Network outreach activities. The HTAN-DCC, HTAN Investigators, and NCI staff will need to work closely together to accomplish the goals of the HTAN-DCC in a manner that will best benefit all HTAN Investigators and the broader scientific community.

Open and Controlled HTAN Data Access -- The NIH promotes broad and responsible sharing of genomic research data and respects the privacy and intentions of research participants. Some data generated by the HTAN will be open access, which means that no authentication or authorization is necessary to access it. Other data generated will be controlled access, which means that the database of Genotypes and Phenotypes (dbGaP) authorization and eRA Commons authentication are necessary for access to this data when the data is made publicly available. Whether a dataset is open or controlled is determined according to NIH Data Access Policies in a process that is driven by informed consent of research participants. Decisions on which data generated by the HTAN are open or controlled access will be made in conjunction with the HTAN, the NCI Program Officer, and the NIH Office of Science Policy.

Open access data generally includes high level genomic data that is not individually identifiable, such as verified somatic variants, as well as most clinical and all biospecimen data elements.

Controlled data generally includes individually identifiable data such as low level genomic sequencing data (BAM, FASTQ files), germline variants, SNP6 genotype data, and certain potentially identifiable clinical data elements. Access to controlled data is granted by program-specific Data Access Committees. dbGaP was developed to archive and distribute the genomic data and results from studies that have investigated the interaction of genotype and phenotype in humans. dbGaP currently manages controlled access to genomic data.

The HTAN DCC will be responsible for housing all data generated by the HTAN. However, while the HTAN DCC will host and share all HTAN data within the network (both controlled and open access data), the HTAN DCC will only distribute open access data to the public. The HTAN DCC will be responsible for submitting any controlled access data generated by HTAN to the appropriate repository (e.g., the Genomic Data Commons, dbGaP) for distribution to the public. Consequently, the HTAN DCC will be responsible for the creation of a system that can distinguish between and segregate controlled-access and open-access data. Because the HTAN DCC will only distribute open access data to the public and will rely on other NIH repositories for distribution of controlled access data the HTAN DCC will not become an NIH Trusted Partner.

For additional details please refer to 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).

Specific activities and roles of the HTAN-DCC will include, but are not limited to:

Data Standards, Storage, Analysis, and Dissemination

• Developing an HTAN Data Portal for user-friendly submission of and access to HTAN data (both raw data and derived datasets), metadata, analysis and visualization tools, computational models, and completed atlases generated by the HTAN. The web-interface should provide controlled-access to both HTAN participants and the broader scientific community, and should be accessible through the main HTAN Web Portal;
• Establishing a back-end database with an application framework to facilitate complex data loading including detailed experimental descriptions and metadata, especially for experimental results generated using high throughput or data-intensive approaches. The database should be flexible and extensible to manage and integrate multiple types of data including but not limited to, genomics, proteomics, molecular and cellular imaging, clinical imaging, spatial information, and epidemiological and clinical data. The database will also need to incorporate 3D spatial data;
• Working closely with HTAN Investigators and NCI staff through HTAN working groups to establish common data elements, data standards, metadata requirements, clinical and epidemiological data requirements, and controlled vocabularies for all HTAN data to ensure that the data are findable accessible, interoperable, and reusable (FAIR) to ensure the data and results are maximally useful to the public;
• Working closely with HTAN Investigators to develop and implement common data submission, processing, and quality control pipelines for the diverse range of HTAN datasets;
• Working closely with HTAN Investigators to implement data analysis and visualization tools at the HTAN Data Portal;
• Working closely with HTAN Investigators to implement completed atlases at the HTAN Data Portal for utilization by the broader research community;
• Working closely with HTAN Investigators to develop a unified platform allowing centralized access and comparative viewing and analysis of all completed atlases
• Developing and sharing tutorials, detailed walkthroughs, and other materials that facilitate use of HTAN-generated data, models, and completed atlases by the broader scientific community;
• Facilitating data use by the broader scientific community by depositing datasets generated by HTAN Investigators in appropriate unrestricted or controlled-access databases and support user-friendly access to these databases;
• Working closely with NCI staff and relevant public data/resource repositories to ensure the long-term archiving and distribution of the most important datasets and resources developed by the HTAN beyond its funding period; and,
• Developing an Application Programming Interface (API) to facilitate interactions with other Cancer Moonshot DCCs and components of the NCI Cancer Research Data Commons.

Consortium Coordination and Outreach

• Developing and maintaining a main HTAN Web Portal that will constitute the main entry point for the sharing of resources and information related to HTAN activities. Develop and implement user-friendly approaches to navigate and access resources generated by the HTAN, including protocols, data standards, biospecimen and reagent information, tutorials, analysis and visualization tools, and completed atlases. The HTAN Web Portal should also include access to the HTAN Data Portal. The HTAN Web Portal will need to be structured in a way that allows for multiple levels of access, based on the level of confidentiality of the data, resource, or information being requested, such as "NCI Staff", "HTAN Investigator" and "Public" access levels;
• Working closely with HTAN Investigators and NCI staff to ensure that all data, protocols, biospecimen and reagent information, analysis and visualization tools, and completed atlases generated or developed by HTAN Investigators are deposited in a timely manner and made accessible through the HTAN Web Portal and/or HTAN Data Portal consistent with the sharing policies of the Cancer Moonshot Initiative and the HTAN;
• Providing the administrative infrastructure necessary to facilitate and coordinate all common activities of the HTAN;
• Working with NCI staff to organize HTAN scientific meetings, including an HTAN Kickoff Meeting and semi-annual 2-3 day in-person HTAN Steering Committee Meetings;
• Working with NCI staff to organize and coordinate HTAN governing and advisory bodies including the HTAN Steering Committee and subcommittees, HTAN working groups, and external scientific panels. Managing these activities by organizing web-based conferences, taking meeting minutes, and drafting reports for the various committees, working groups, and panels. Developing and making accessible all significant HTAN-related documents, including policies, reports, and standard operating procedures generated by the various HTAN committees;
• Facilitating other HTAN activities, including but not limited to: organizing small topical workshops; collaborations with outside groups; implementation of HTAN developed policies; and facilitating consortium opinion and perspective pieces;
• Facilitating interactions with other Cancer Moonshot-supported research efforts, other NCI and NIH supported efforts, and/or non-NIH partners. These may include consortia, bio-repositories, databases, or non-profit organizations involved in activities relevant to the mission of the HTAN. The focus should be on developing interactions that can benefit both investigators and partners of the HTAN through the sharing of information, expertise, and reagents, or through leveraging the coordination of research and technology development in areas of common interest; and,
• Managing or facilitating other outreach activities, including but not limited to, organizing sessions and tutorials at scientific meetings and managing the HTAN social media presence.

Development of the HTAN-DCC will require the DCC team to work closely with all components of the HTAN, including funded investigators and NCI staff, to establish data and metadata standards, develop data submission and processing pipelines, establish data freezes and public release of data, and coordinate data integration and analysis. We anticipate that most datasets handled by the DCC will be next-generation sequencing data, proteomics data, and molecular and clinical imaging data. There will also be a spatial component to the data and associated clinical and epidemiological data. However, it is difficult to predict the exact volume and types of data that will be submitted over the lifetime of the HTAN Program. Increasing efficiencies in generating data along with potential changes in technology platforms may dramatically alter the types and volume of data to be stored, curated, and analyzed by the HTAN-DCC. Additionally, HTAN data will likely be generated across many disease types and cancer-relevant transitions, adding another layer of complexity to the curation and mining of the data. HTAN-DCC should demonstrate the expertise and flexibility to accommodate increasing data volume and evolving data types.

The HTAN-DCC is also expected to evolve, adapt and improve during the project in response to the needs of the HTAN community. The DCC team should solicit user feedback and otherwise evaluate all aspects of the usability of the HTAN Web Portal and Data Portal to best serve the needs of the HTAN and broader research community. As the data generation, storage, analysis, and dissemination needs of the HTAN evolve over time, the DCC may be asked to implement modifications to its workflows as agreed upon by the HTAN Investigators and NCI staff. The DCC should be flexible in their implementation of data coordination, analysis, and outreach workflows.

Structure and Coordination of the Human Tumor Atlas Network

Human Tumor Atlas Network (HTAN) overall organization: The HTAN will consist of Human Tumor Atlas (HTA) and Pre-Cancer Atlas (PCA) Research Centers and the HTAN Data Coordinating Center (HTAN-DCC) solicited under three separate FOAs in Fiscal Year 2018. In Fiscal Year 2019 it is anticipated that a HTAN Tissue Coordinating Center (HTAN-TCC) will be added to the Network to provide a virtual resource for investigators to discover and share available biospecimens across the HTAN. The HTAN will function as a collaborative network allowing Research Centers to cross-test ideas, integrate diverse data sets, and validate (or refute) hypotheses derived from analysis of HTAN data. HTAN-DCC applicants are encouraged to read the HTA (RFA-CA-17-034) and PCA (RFA-CA-17-035) Research Centers RFAs for more information regarding data generation and atlas construction.

Governance of the HTAN: All components will be governed by the HTAN Steering Committee (see Section VI: Terms and Conditions of Cooperative Agreement.) with representatives from the funded HTA and PCA Research Centers, the HTAN-DCC, the HTAN-TCC, and NCI Program staff.

Evaluation of the Program: As the efficiency of the funded research is an important priority for NCI, HTAN-DCC and HTA and PCA Research Centers will be expected to participate in an external evaluation process of the HTAN coordinated by NCI Program Staff (see Section VI: Terms and Conditions of Cooperative Agreement.)

Cancer Moonshot Public Access and Data Sharing Policy:

Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded as part of the Beau Biden Cancer Moonshot^SM Initiative that requires applicants to submit a Public Access and Data Sharing Plan that (1) describes their proposed process for making resulting publications and to the extent possible, the underlying primary data immediately and broadly available to the public upon publication; (2) if applicable, provides a justification to NCI if such sharing is not possible. NCI will give competitive preference and funding priority to applications that comply with the strategy described here. The data sharing plan will become a term and condition of award. Data and computational tool sharing by HTAN members will follow FAIR (findable, accessible, interoperable, and reusable) principles as defined here.

Incomplete Applications

The following types of applications are incomplete and will not be reviewed.

• Applications that do not address all sub-sections described in the Research Strategy instructions (see Section IV.2: Content and Form of Application Submission - PHS 398 Research Plan).

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

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to 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
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

• Dun and Bradstreet Universal Numbering System (DUNS) - All registrations require that applicants be issued a DUNS number. After obtaining a DUNS number, applicants can begin both SAM and eRA Commons registrations. The same DUNS number must be used for all registrations, as well as on the grant application.
• System for Award Management (SAM) (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.

An investigator designated as the Contact PD/PI of an application under this FOA must not be the designated Contact PD/PI of another application under the companion HTAN FOAs RFA-CA-17-034 and RFA-CA-17-035

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

Applicant organizations may submit more than one application, provided that each application is scientifically distinct. Institutions submitting an application to this FOA are allowed to submit an application to the companion FOAs RFA-CA-17-034 and RFA-CA-17-035 provided that each application is scientifically distinct.

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

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

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, including Supplemental Grant Application Instructions 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.

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

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

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

The letter of intent should be sent to:

Sean E. Hanlon, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3310
Email: NCI_HTAN_Data@mail.nih.gov

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

For this specific FOA, the Research Strategy section is limited to 30 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.

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. In addition, applicants should:

• Demonstrate strong scientific expertise in the areas that are critical to the success of the application.
• Describe any experience in successfully leading the coordination of data intensive activities and management and analysis of high-throughput datasets such as those to be generated by the HTAN.

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

Leadership Effort Commitment: The HTAN-DCC contact PD/PI must commit and maintain through the life of the award a minimum of 1.8 person-months of effort. For applications with multiple PDs/PIs, a minimum effort of 1.8 person-months is required for the Contact PD/PI and 1.2 person-months of effort per additional PD/PI is required.

HTAN-DCC Administrator: Based on the complexity of the HTAN-DCC, the DCC PD(s)/PI(s) are strongly encouraged to propose and budget for an HTAN-DCC Administrator to manage day-to-day operations and work with the DCC PD(s)/PI(s), NCI staff, and HTAN Investigators to manage and coordinate the DCC activities.

Travel Funds: The budget should include funds to support travel for HTAN activities, including but not limited to supporting the travel and participation of PD(s)/PI(s) and other HTAN-DCC members at the semi-annual HTAN Steering Committee meeting and annual site visits.

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:

Specific Aims: Specific Aims should address the three subsections described below (DCC Vision and Management; Data Standards, Storage, Analysis, and Dissemination; and Consortium Coordination and Outreach).

Research Strategy: In lieu of the standard sub-sections listed in the SF424 (R&R) Application Guide, the Research Strategy must consist of the following modified sub-sections.

Sub-Section A: DCC Vision and Management

Overview and Goals Applicants should describe the ultimate goals/deliverables of the HTAN-DCC. Deliverables should be quantitative whenever possible and would include items such as:

• Develop and release an HTAN Web Portal;
• Develop and release an HTAN Data Portal;
• Establish network-wide consensus for data formats and metadata requirements;
• Establish network-wide consensus for a data release policy;
• Develop and implement data submission, processing, quality control assessment, and download pipelines;
• Establish semi-annual in-person HTAN Steering Committee meetings
• Implement analysis and visualization tools developed by HTAN Investigators at the HTAN Data Portal;
• Implement completed atlases at the HTAN Data Portal; and,
• Develop user manuals and tutorials for the HTAN Data Portal and Web Portal.

As mentioned above, it will be difficult to predict the exact volume and types of data that will be submitted over the lifetime of the HTAN Program. As the data production, storage, analysis, and dissemination needs of the HTAN change with time, the HTAN-DCC may be asked to implement modifications to their workflow and deliverables and applicants must demonstrate their willingness and aptitude to be flexible in their implementation of HTAN coordination.

Milestones and Progress Applicants should define a clear set of semi-annual milestones with metrics that will document progress towards the achievement of the ultimate goals. Quantitative milestones are required to provide clear indicators of a project's continued success or emergent difficulties and will be used to evaluate the application not only in peer review but also in consideration of the awarded project for funding of non-competing award years. Examples include, but are not limited to, milestones that track time to develop data standards and formats, turn-around time to release submitted data and completed atlases, or analysis and visualization software implementation activities. Applicants should include plans for critically evaluating and revising these milestones on a regular basis. Applicants should describe how they will prioritize their activities to ensure that the main goals of the DCC will be achieved. Milestones may be revised at the time of the award. Applicants should also describe plans to solicit user feedback, monitor metrics of DCC usage, and otherwise evaluate all aspects of the usability of the HTAN-DCC. This plan should describe the frequency of these evaluations and how this information will be used to improve the utility of the HTAN-DCC.

Management and Communication Plan Applicants should describe the plans for management and integration of the HTAN-DCC activities. Applicants should describe how it will manage the proposed project, who will oversee the day-to-day activities (e.g., a DCC Administrator if not the PD/PI) and how the management structure will support achievement of the proposed goals and milestones. Useful elements of this description include the organization of the proposed project; its management structure; key personnel and leadership structure; and oversight mechanisms for evaluating progress towards milestones. Applicants should describe plans for ongoing communication within the HTAN-DCC and between the DCC and other components of the HTAN. Plans for addressing some of the anticipated challenges of the DCC should also be included. The plan should also describe how the various elements of the proposed production effort will be integrated, and how collaborations or subcontracts, if proposed, will be managed.

Sub-Section B: Data Standards, Storage, Analysis, and Dissemination

Data Portal Development Applicants should describe plans for developing a data portal that can be accessible through the main HTAN Web Portal. The HTAN Data Portal will provide user-friendly submission of and access to HTAN data (both raw data and derived datasets), metadata, analysis and visualization tools, computational models, and completed atlases generated by the HTAN. The web-interface should provide access to both HTAN members and the broader scientific community. Applicants should describe a submission pipeline for both raw and derived datasets generated by HTAN Investigators. Each submitted dataset must be assigned a unique identifier that enables subsequent tracking for submitted data of all types. This pipeline must include quality assurance steps to monitor the quality of the submitted data and metadata, along with steps to release these data and metadata to the public data portal in a timely fashion. Please see Open and Controlled HTAN Data Access for a description of the types of accessible data for HTAN members and the broader scientific community. As the identity of the actual funded projects will not be known at the time that the applications in response to this FOA are due, applicants should provide a general submission plan. It is anticipated that most datasets handled by the DCC will be next-generation sequencing data, proteomics data, and molecular and clinical imaging data. There will also be a spatial component to the data and associated clinical and epidemiological data. The plan should describe how the DCC will handle a range of data types and how the DCC will provide the flexibility to accommodate increasing data volume and evolving data types. The plan should describe the capacity to scale activities as data volumes or complexity change over the course of the project. At the end of the project, the DCC must be able to transfer the HTAN data to any other informatics resource, as designated by the NIH.

Data Security -- Applicants should provide a plan for satisfying federal data security regulations. The HTAN DCC will be considered federal electronic information systems and as such, must meet the relevant federal 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 Federal Information and the Federal Information system. 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. This policy is in accordance with the Federal Information Security Management Act (FISMA).

The core data sets defined for the HTAN are categorized as Federal Information Management Security (FISMA) Low. The security requirements for this DCC implementation include, but are not limited to, preparation of an IT Security Plan, IT Risk Assessment, FIPS 199 Assessment, and performance of security control testing and evaluation. The awardees will be responsible for attaining the Authority To Operate (ATO) from the NCI Program Officer.

Additionally, any proposed solutions using a commercial cloud must demonstrate an understanding of FedRAMP requirements (http://www.fedramp.gov) and describe an approach for achieving compliance if FedRAMP has not yet been achieved.

Data Storage and Access Applicants should describe a plan for where and how all data, metadata, analysis and visualization tools, computational models, and completed atlases generated by the HTAN will be stored. The data, tools, models, and atlases may be stored on a commercial cloud, local private servers, existing public data repositories, or a combination of these solutions. The plan should include a description of why specific solutions are being implemented and how those advance the overall goals of the DCC and the HTAN.

The HTAN DCC will be responsible for housing all data generated by the HTAN. However, while the HTAN DCC will host and share all HTAN data within the network (both controlled and open access data), the HTAN DCC will only distribute open access data to the public. The HTAN DCC will be responsible for submitting any controlled access data generated by HTAN to the appropriate repository (e.g., the Genomic Data Commons, dbGaP) for distribution to the public. The data storage plan should describe a system that can distinguish between and segregate controlled-access and open-access data.

Information Technology and Technology Development Applicants should discuss all pertinent informatics issues involved in providing the basic IT infrastructure/system administration for the proposed project. The plan should describe a framework to facilitate complex data loading including detailed experimental descriptions and metadata, especially for experimental results generated using high throughput or data-intensive approaches. The database infrastructure should be flexible and extensible to manage and integrate multiple types of data that may be generated by HTAN Investigators, including genomics, proteomics, molecular and cellular imaging, clinical imaging, clinical and epidemiological data, and spatial information. Incremental technology improvements may play an important role in increasing the efficiency and decreasing costs for the DCC. Applicants are encouraged to include plans for such technology development activities in their applications, such as supporting new software tools to improve data management or making existing software more efficient (e.g., improving sequence read alignment software or data processing pipelines). The plans for technology improvement should be well described and the cost of the proposed technology development should be justified in terms of reducing the overall operating costs for the DCC. Additionally, applicants should describe a plan to develop an Application Programming Interface (API) to facilitate interactions with other Cancer Moonshot data coordinating centers and components of the Cancer Data Ecosystem.

Interactions with HTAN Data Producers Development of the HTAN-DCC will require the DCC team to work closely with HTAN Investigators and NCI staff. Applicants should describe plans and strategies for facilitating interactions that allow the efficient development of the DCC. DCC tasks that will require significant interaction with other members of the HTAN program include, but are not limited to:

• Work with HTAN Investigators and NCI staff to establish standardized machine readable data formats and common data elements using well-defined formats and associated controlled vocabularies.
• Work with HTAN Investigators and NCI staff to define standard experimental metadata, epidemiological data, and clinical data required to be submitted with each dataset.
• Work with HTAN Investigators to develop data submission, processing, and quality control pipelines for all data types that will be submitted to the DCC.
• Work with HTAN Investigators to facilitate the timely and efficient transfer of data, metadata, and completed atlases to the DCC.
• Work with HTAN Investigators and NCI staff to establish regular data freezes to quantify productivity and facilitate analysis activities.
• Work with HTAN Investigators and NCI staff to establish a public data release policy. The DCIC will need to be flexible and responsive in following the evolving NIH policies on data sharing.

Data Wrangling The DCC must provide mechanisms and staff to interact with the data production groups to facilitate the timely and efficient transfer of data, metadata, and completed atlases to the DCC. Applicants should describe plans for working closely with HTAN Investigators and NCI staff to ensure that all data and metadata, protocols, biospecimen and reagent information, analysis and visualization tools, and completed atlases generated or developed by HTAN Investigators are deposited in a timely manner and made accessible through the HTAN Web Portal and/or HTAN Data Portal consistent with the sharing policies of the Cancer Moonshot Initiative and the HTAN.

Implementation of Analysis and Visualization Tools Applicants should describe plans to implement analysis and visualization tools developed by HTAN Investigators at the HTAN Data Portal. Priority should be given to tools and software that are modular, open-source, include appropriate documentation, use standard formats for data input and output, and are considered likely to be broadly useful to HTAN Investigators.

Centralized Access and Comparative Analysis of Atlases The DCC will provide centralized access to all completed tumor atlases generated by the HTA and PCA Research Centers. In addition, the Data Portal should develop a unified platform that will integrate all atlases to enable comparative viewing and analysis. Applicants should describe their visions and plans to implement these capabilities.

Data Export and Dissemination Applicants should describe plans for developing an export process and pipeline to permit timely transfer of HTAN data from consortium data freezes or publications to appropriate public repositories and community databases to ensure the long-term availability of HTAN generated data. These repositories may include, but are not limited to, the NCI Genomic Data Commons (GDC), the Cancer Imaging Archive (TCIA) at the National Cancer Institute, the database of Genotypes and Phenotypes (dbGAP) at the National Center for Biotechnology Information (NCBI), ArrayExpress at the European Bioinformatics Institute (EBI), Ensembl at the EBI and the Wellcome Trust Sanger Institute, or a Network-wide instance of OMERO from the University of Dundee and Open Microscopy Environment. Regardless of where datasets are deposited, the HTAN-DCC will facilitate user-friendly access to the open access HTAN-generated data and metadata for the duration of the Program. Data and metadata must be available in standard formats and adhere to the FAIR (findable, accessible, interoperable, and reusable) principles to ensure the data and results are maximally useful to members of HTAN and the broader scientific community.

Sub-Section C: Network Coordination and Outreach

Web Portal Development Applicants should describe a plan for developing and maintaining the main HTAN Web Portal that will constitute the main entry point for the sharing of resources and information related to HTAN activities. The HTAN Web Portal should provide user-friendly access and navigation to resources generated by the HTAN, including protocols, data standards, biospecimen and reagent information, tutorials, analysis and visualization tools, and completed atlases. HTAN Web Portal should also include access to the HTAN Data Portal. The HTAN Web Portal should allow for multiple levels of access, based on the level of confidentiality of the data, resource, or information being requested, such as "NCI Staff", "HTAN Investigator" and "Public" access levels.

HTAN Activity Coordination Applicants should describe an approach to provide the administrative infrastructure necessary to facilitate and coordinate all common activities of the HTAN. HTAN activities that will be coordinated by the HTAN-DCC will include: semi-annual 2-3 day HTAN in-person Steering Committee Meetings and focused workshops, monthly HTAN virtual Steering Committee and subcommittees, virtual HTAN working groups, and external scientific panels. The plan should describe approaches for managing these activities through in-person or web-based meetings, developing minutes, and drafting reports for the various committees and working groups. Additionally, the plan should describe an approach to develop, maintain, and make accessible all significant HTAN-related documents, including policies, reports, and standard operating procedures generated by the various HTAN committees, working groups, and panels. The plan should also include approaches to facilitate interactions and collaborations with outside groups other Cancer Moonshot-supported research efforts, other NCI and NIH supported efforts, and/or non-NIH partners.

Outreach, Documentation and User Support Applicants should describe a plan and allocate sufficient resources to provide outreach to the user communities to educate the community about the HTAN and its data, resources, tools, and completed atlases. This plan should include resources for both specialists and non-specialists to make the best use of the HTAN data, computational models, tools, and completed atlases. Examples include presentations, short courses, or symposia offered independently or in conjunction with scientific meetings attended by the user community. Provide plans to develop and update HTAN DCC user documentation to be made available on the Web Portal such as User's guides, FAQs, Troubleshooting Tips, web-based tutorials and other content to assist HTAN DCC data consumers, data providers, and general users.

Describe typical user support activities to be performed by the HTAN DCC staff including, but not limited to, receiving and addressing user inquires, providing email support, maintaining publicly accessible website for helpdesk operations, providing news and announcements, hosting application use reports, frequently asked questions and troubleshooting tips, and providing summary reports of questions and responses, including frequency of inquiries and duration between inquiry and resolution as appropriate.

Sub-section D: Health Disparities

If applicable to the type of research being proposed, address how minority or health disparity populations or data will be integrated into the proposed studies. Highlight, as relevant, any opportunities that, if implemented, can reduce the burden of cancer in the health disparities that currently exist. In this context, efforts are encouraged to address the needs of minority populations and other health disparity populations, including those from urban and rural areas who are poor and medically underserved, who continue to suffer disproportionately from certain cancers and have higher morbidity and mortality rates.

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.
• The plan should describe the types of data, software, and models that are expected to be generated and shared.
• Data, software, and models from this FOA are expected to be shared in an easily accessible format with the scientific community to increase the value of the significant public investment. Note that the NCI Program staff may negotiate modifications to these plans prior to funding (see Section VI: Terms and Conditions of Cooperative Agreement).
• Applicants should consider pre-existing intellectual property rights associated with the use of existing technologies/models. If proprietary tools/devices are used in building the data coordinating center and/or atlas(es), applicants should clearly state the licensing agreement and are advised to contact NCI and seek assistance as needed from the NCI Technology Transfer Center (https://ttc.nci.nih.gov/) in determining whether such arrangements are appropriate and/or adequate.
• Addressing the Cancer Moonshot Open Access Pilot Program: Utilizing the provision outlined in the 21st Century Cures Act, NCI has established a data sharing policy for projects that are funded as part of the Beau Biden Cancer MoonshotSM Initiative that requires applicants to submit a Public Access and Data Sharing Plan that: (1) describes their proposed process for making resulting publications and to the extent possible, the underlying primary data immediately and broadly available to the public upon publication; and (2) if applicable, provides a justification to NCI if such sharing is not possible. NCI will give competitive preference and funding priority to applications that comply with the strategy described here. The data sharing plan will become a term and condition of award.
• Guiding Principles for Cancer Moonshot Biobanking Activities: The goal in developing these guiding principles is to accelerate research by a) increasing the availability of biospecimens for Cancer Moonshot-related and other biomedical research through facilitation of investigator to investigator sharing of biospecimens, and b) increasing the reproducibility of Cancer Moonshot research through improved biospecimen practices and corresponding annotation. These guiding principles also seek to facilitate, where possible, increased engagement of research participants through researchers' communication of aggregate research results and, in some cases, individual genomic findings that may be medically actionable for research participants. NCI will give competitive preference and funding priority to applications that conform to the "Guiding Principles for Cancer Moonshot Biobanking Activities" (http://biospecimens.cancer.gov/programs/cancermoonshot/principles) and are consistent with the "2016 NCI Best Practices for Biospecimen Resources" (https://biospecimens.cancer.gov/bestpractices/).

Appendix:

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

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

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

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

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

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

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

This initiative is not subject to intergovernmental review.

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

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

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

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 the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

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

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

Does the proposed Data Coordinating Center address the needs of the research Human Tumor Atlas Network (HTAN) that it will coordinate? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research Network?

Specific to this FOA: What is the likelihood that DCC, as proposed, will meet all the data management, consortium coordination, and outreach needs of the HTAN? Will the proposed DCC be able to meaningfully contribute to HTAN, e.g., by resolving major challenges in data management, consortium coordination, and outreach?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Data Coordinating Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing multidisciplinary research? Do the investigators demonstrate significant experience with coordinating collaborative large-scale omics and imaging based research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, management plans, governance, plans for conflict resolution, and organizational structure appropriate for the Data Coordinating Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA: How well do the PD(s)/PI(s) demonstrate evidence of experience working productively in collaborative environments and in large, distributed scientific projects?

Does the application propose novel data management, network coordination, and outreach strategies in coordinating the research Network the Data Coordinating Center will serve? Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of data management, network coordination, and outreach strategies proposed?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research Network the Data Coordinating Center will serve? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the Network, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the Network is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the Network? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this FOA: How well does the research plan address the HTAN-DCC's three major areas of responsibilities (1) Data Storage, Dissemination, Analysis, and Visualization; (2) Consortium Coordination and Administration; and (3) Dissemination and Outreach? Does the application contain acceptable plans for addressing the NCI Cancer Moonshot Public Access and Data Sharing Policy?

Will the institutional environment in which the Data Coordinating Center will operate contribute to the probability of success in facilitating the research Network it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Data Coordinating Center proposed? Will the Data Coordinating Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this FOA: Is the computational infrastructure adequate to meet the needs of the project? How well does the environment promote the collaborations, transdisciplinary approaches, and flexibility required to solve the technical and scientific problems of the proposed HTAN-DCC?

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

As part of the scientific peer review, all applications:

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

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

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

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Compliance with Beau Biden Cancer Moonshot Open Access and Data Sharing Policy

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

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

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

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

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

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

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

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person's race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator's scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

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

Cooperative Agreement Terms and Conditions of Award

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

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

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

• Planning and conducting the operations defined by the terms and conditions of the cooperative agreement award.
• Overseeing the scientific development of the Data Coordinating Center, reporting results to the scientific community, and disseminating approaches, methods, models, software, tools, and atlases broadly.
• Committing and maintaining throughout the life of the HTA Research Center a minimum of 1.8 person-months of effort per year for the investigator designated as the contact PD/PI.
• Committing and maintaining throughout the life of the HTA Research Center a minimum of 1.2 person-months of effort per year for any investigator designated as a MPD/MPI of the Research Center.
• Agreeing to be an active participant in the HTAN, including attending the semi-annual Steering Committee Meetings, participating in other network sponsored meetings and workshops, and participating in collaborative activities.
• Serving on the HTAN Steering Committee. The HTAN-DCC PD/PI (contact PD/PI for applications with multiple PD(s)/PI(s)) is required to serve as members of the Steering Committee.
• Abiding by the governance of the HTAN and all program policies agreed upon by the HTAN Steering Committee and approved by NCI Program Officials to the extent consistent with the applicable rules and regulations.
• Maintaining the confidentiality of the information developed or handled by the HTAN-DCC, including, but not limited to: unpublished data, informatics tools, protocols, data analysis, confidential exchanges between members of the HTAN, etc.
• Working closely with HTAN data generators to ensure that data, metadata, models, software, and completed atlases developed by the HTAN are deposited in the HTAN Data Portal in a timely manner that is consistent with HTAN policies.
• Leveraging, where feasible, technology from related NCI-sponsored informatics initiatives, for example the NCI Informatics Technology for Cancer Research (ITCR) program, which supports the development of informatics algorithms, tools, and resources across the continuum of cancer research.
• Coordinating with and leveraging, where feasible, the technology of the NCI Cancer Research Data Commons, a program that will provide infrastructure to make diverse cancer research data broadly available and to maximize their reuse and impact.
• Facilitating the public release and dissemination of results, data, reagents, technologies, completed atlases, and other products generated by HTAN Investigators in a timely manner, consistent with achieving the goals of this program. The release and dissemination will be consistent with sharing policies and recommendations developed and approved by the HTAN Steering Committee and NIH sharing policies.
• Prior to completion or termination of the HTAN-DCC project, the Awardee, in consultation with NCI program staff, is responsible for ensuring all data, metadata, models, software, and completed atlases developed by the HTAN remains accessible to the research community.
• Organizing scientific working groups to facilitate collaborative projects and cross-testing of experimental and analytical concepts.
• Reporting progress to the NCI Program Officials on all HTAN-DCC activities annually. The PD(s)/PI(s) may be expected to provide additional information, outside the scope of the standard reporting requirement, as needed and requested by program staff members as requested.
• Being prepared for the annual site visits of NCI Program staff members and participation in the NCI-coordinated evaluation of the HTAN program.
• Meeting annually with other Moonshot U24 coordinating centers to help coordinate the sharing of data, research resources, tools/platforms, and access to newly established biorepositories across the Moonshot initiatives.

Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies. Participating HTA Research Center members are also encouraged to organize and participate in other HTAN meetings and workshops, organize collaborative activities, and promote Trans-Network collaborations, and organize and participate in scientific and programmatic working groups.

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

One or more designated NCI Program staff members will have substantial involvement as Project Scientist(s) for the HTAN.

Additionally, an NCI Program Director acting as Program Official will be responsible for the normal scientific and programmatic stewardship of the award and will be named in the award notice. Program Officials may also have substantial programmatic involvement (as Project Scientists).

In carrying out its stewardship of Beau Biden Cancer Moonshot initiatives, the National Cancer Institute (NCI) will monitor and evaluate progress to meet the expectations set forth by Congress in the 21st Century Cures Act.

The specific roles of the substantially involved NCI staff members include the following activities:

• Serving as non-voting members of the HTAN Steering Committee.
• Assisting the Steering Committee, the HTAN Data Coordinating Center, and individual U2C awardees in avoiding unwarranted duplications of effort across the HTAN.
• Facilitating collaborative research efforts that involve multiple HTAN Research Centers and would be suitable for consideration as a trans-HTAN collaborative project to be funded by restricted Research Center funds.
• Assisting the awardees as a resource in facilitating their broader interactions with other NCI and NIH programs to disseminate results, tools, and models from the HTAN and take advantage of existing NIH/NCI resources and infrastructures. This will specifically include acting as a liaison between the HTAN and other atlas-building programs.
• Ensuring that the HTAN Data Coordinating Center data- and tool-sharing infrastructure is provided to HTAN members in a reasonable and expeditious way.
• Evaluating the effectiveness and facilitating consortium-wide adoption data- and tool-sharing and interoperability practices.
• Monitoring the operations of the HTAN awardees and making recommendations on overall project directions and allocations of HTA Research Center funds.
• Reviewing the progress of the HTAN awardees (including HTAN Data Coordinating Center), conducting periodic site visits, and taking other actions as needed.
• Participating in organizing semi-annual HTAN meetings, specialized workshops, and webinars of the network.

Areas of Joint Responsibility include:

Steering Committee: The Steering Committee will be the main governing body for the HTAN. The Steering Committee will be composed of one representative (contact PD/PI or other senior level investigator) from each HTAN awardee, i.e., from HTA Research Centers, PCA Research Centers, and HTAN Data Coordinating Center and HTAN Tissue Coordinating Center who will have one vote each.

NIH/NCI program staff members will participate in HTAN Steering Committee meetings as non-voting members.

If needed, other government staff members may also participate in HTAN Steering Committee meetings as non-voting members.

Two PD(s)/PI(s), representing two different HTAN awards, will be selected to serve as chairpersons of the Steering Committee starting at the first meeting of the Steering Committee following award issuance. All HTAN Steering Committee decisions and recommendations that require voting will be based on a majority vote.

The HTAN Steering Committee will meet monthly by videoconference and in-person at the HTAN semi-annual Steering Committee Meeting and as needed.

The HTAN Steering Committee will:

• Identify scientific and policy issues that need to be, or can benefit by being, addressed at the Network level and develop recommendations to NIH/NCI Program Officials for addressing such issues.
• Review progress of the HTAN toward meeting the overall Network goals.
• Ensure that all HTAN members utilize the resources developed by the HTAN-DCC and HTAN-TCC.
• Discuss and prioritize the collaborative projects to be supported by the restricted "HTAN Collaborative Project" funds within each Research Center.
• Coordinate dissemination of Network output to the broader cancer research community.
• Ensure that the Network takes advantage of existing NCI and NIH resources and programs.
• Establish, as necessary, subcommittees to ensure progress of the individual Centers and the Network.

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

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

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

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

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

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

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

Email: support@grants.gov

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

Telephone: 301-945-7573

Sean E. Hanlon, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3310
Email: NCI_HTAN_Data@mail.nih.gov

Craig Giroux, Ph.D.
NIH Center for Scientific Review
Telephone: 301-435-2204
Email: girouxcn@mail.nih.gov

Crystal Wolfrey
National Cancer Institute (NCI)
Telephone: 240-276-6277
Email: wolfreyc@mail.nih.gov

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

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