Required Application Instructions

It is critical that applicants follow the 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

This funding opportunity announcement (FOA) is a part of cancer genomics programs supported by the National Cancer Institute (NCI) and managed by its Center for Cancer Genomics (CCG). The overall goal of these programs is to help elucidate the mechanisms of cancer initiation and evolution, as well as resistance to therapy by means of genomic characterization of well-annotated, high quality tumor samples. This resulting knowledge could facilitate and accelerate the development of new diagnostic and prognostic markers, new targets for pharmaceutical interventions, and new cancer prevention and treatment strategies.

This FOA solicits applications for a Processing Genomic Data Center that will be a part of the Genomic Data Analysis Network. The network will also include other types of Genome Data Analysis Centers (GDACs) to be supported under companion FOAs, RFA-CA-15-019 and RFA-CA-15-020).

Data to Be Analyzed by GDACs. Genomic data to be analyzed by the Genomic Data Analysis Network will primarily originate from a network of Genomic Characterization Centers (GCCs, that are supported by the NCI separately through contracts). To generate these data, GCCs will utilize high-throughput, high resolution technologies to comprehensively (i.e., genome-wide) detect genomic, epigenomic and transcriptomic aberrations including: alterations in chromosome segment copy numbers, translocations, loss of heterozygosity, altered DNA methylation patterns and changes in gene expression, which may play a role in cancer.

Goals for the Genomic Data Analysis Network. The overarching goal is to enable the cancer research community to develop tools and strategies to analyze the data generated from large-scale genomics projects and support the scientific community at-large in their investigation of the results.

Up to 14 multi-disciplinary, interactive GDACs will be established under this FOA and its companions (RFA-CA-15-019 & RFA-CA-15-020). All GDACs will work together as a network to:

• Develop a strategy for data flows from the DCC/GDC to the GDACs
• Determine the various types of analyses to be performed that are relevant to the needs of the analysis working groups; and
• Optimize the mechanism(s) for communicating back to the stakeholders in the project as well as the scientific community. GDACs will also be responsible for submitting their results on the identified cancer-associated molecular alterations to the Data Coordinating Center (DCC)/Genomics Data Commons (GDC).

Goals for the "Processing" Type GDAC to be supported under this FOA. The Processing type GDAC will be expected to focus on the following aspects:

• Developing and implementing appropriate bioinformatic systems for rapid high-throughput processing, integration and standardization of genome-wide datasets generated by the GCCs (and other network participants);
• Create a biology-centric computational pipeline for more advanced analyses and identify potential translational directions and outcomes from omics data.

The pipeline is designed to be deployable at various institutions (i.e., not to operate exclusively at the pipeline producer’s home institution, nor have location dependencies that hampers deployment at another site). This pipeline must operate in an essentially automated fashion to produce a standardized output for all CCG-designated projects that will serve as the base analysis for the other GDACs to use in the in-depth exploration of the data. It is expected that a single award of this class will be made.

Note on Key Terms Used in the FOA:

• The term characterization (in the context of cancer-related genomic alterations) refers to the generation of molecular data from biospecimens (by the GCCs or other relevant sources indicated by the NCI).
• The term analysis refers to various types of bioinformatic analyses of data and integration of results via bioinformatic approaches and use of computational tools.

Genomic and Epigenomic Abnormalities in Cancer. Cancer is a complex and heterogeneous disease, in which mutations and other genomic and epigenomic abnormalities play a role in both its initiation and progression. Accumulated research data implicate numerous somatic mutations and a more limited number of inherited mutations in carcinogenesis. Understanding cancer-specific somatic mutations can provide important clues regarding the molecular processes underlying the development and progression of certain tumors. Given cancer’s complexity, it is generally believed that only a fraction of alterations that may be useful as characteristic markers of specific tumor types and/or potential molecular targets have been identified to date. Therefore, to be successful, comprehensive genomic analyses of cancer must overcome a broad range of challenges stemming from the biological complexity and heterogeneity of human tumors and subtypes. An important role in tumor heterogeneity is played by the genomic instability, which is inherent to the progression of cancer. The dynamic changes in tumor genomes are influenced by the cellular and biological context, genetic characteristics of individual persons, and environmental factors. Certain similarities exist across tumor types, however any effort to characterize the genomes of tumors in a comprehensive, systematic manner must address the heterogeneity across distinct cancer types and subtypes.

Characterization of Cancer-related Abnormalities--The Cancer Genome Atlas (TCGA). Many research groups are working independently to identify cancer-relevant genomic changes (e.g., alterations in expression profiles, chromosome deletions, amplifications, and/or translocations) in a relatively small number of samples. Cancer-relevant changes have been detected at diverse levels of genomic organization; they include point mutations, chromosomal deletions, amplifications, translocations, and/or changes in the number of individual chromosomes, all of which can, in principle, contribute to transcriptional aberrations. To produce a comprehensive catalog of cancer-specific alterations, in 2006, the NCI and the National Human Genome Research Institute initiated a collaboration to pursue a 3-year pilot project (The Cancer Genome Atlas, TCGA) to determine the feasibility of more comprehensively cataloging the genomic alterations associated with a small number of different human cancers. The pilot project focused mainly on three tumor types: glioblastoma multiforme, serous cystadenocarcinoma of the ovary, and squamous carcinoma of the lung. The pilot project expanded to approximately 30 additional tumor types over the next 4 years and as of 2015 represents approximately 2.5 petabytes (PB) of data on over 11,000 cases of human cancer. Data analysis to date demonstrates that cancer-associated genes and genomic regions can be identified by combining diverse information from genome analyses with tumor biology and clinical data, and that the sequencing of selected regions can be conducted efficiently and cost-effectively.

The strength of TCGA was to produce unprecedented multi-dimensional data sets using an extended number of samples to provide statistically robust results that sets the stage for a new era in the discovery of new cancer interventions. The integrative analyses leading to the formulation of an unanticipated hypothesis on a potential mechanism of resistance highlights precisely the value and power of such project design, demonstrating how unbiased and systematic cancer genome analyses of large sample cohorts can lead to important discoveries

Three key lessons learned from the TCGA project were that to be able to interpret the results generated by the various characterization platform the Centers had to utilize high quality molecular analytes; perform experiments utilizing strict standardized protocols; and deposit the results in structured formats in publicly accessible databases. The last lesson strongly impacted on the ability of the various analytical groups to extract meaningful results from the genomic data generated. The unique aspect of the TCGA Project was the development and function of an integrated research network. Due to the TCGA success, it is envisioned that all future NCI-sponsored genomics projects will utilize a similar model.

General Directions for NCI-supported Cancer Genomics Efforts. The intent of NCI is to continue a coordinated and comprehensive, genome-wide analysis of cancer-relevant alterations by simultaneously applying several technologies to interrogate the genome, epigenome, or transcriptome in large collections of quality controlled cancer biospecimens derived from specific cancer types. To accomplish this goal, the NCI supports various programs, which are coordinated by its Center for Cancer Genomics (http://www.cancer.gov/about-nci/organization/ccg). Research under these programs is conducted by multidisciplinary teams of investigators and associated institutions that collectively provide biological data, as well as inform strategies for sequencing. The progress in understanding some cancer-associated molecular alterations and the accompanying advances in technology suggest that it is now possible to obtain comprehensive genomic information from multiple tumor types to catalog most, if not all, of the genomic changes associated with cancer and correlate the molecular data with clinical parameters and outcomes to solve hereto unanswered clinical questions. Ultimately, in collaboration with and in support of the NCI s extensive program of individual projects in cancer research, such efforts are expected to accelerate the identification of markers for prevention and diagnosis and novel targets for the development of therapeutic drugs, as well as provide the basis for a refined clinical understanding of patient stratification in therapy.

Expectations for GDACs in the Genomic Data Analysis Network. As a whole the GDACs must be able to:

• Implement bioinformatic pipelines using existing state-of-the-art tools for timely high-throughput processing and integrated analyses of genome-wide data;
• Develop and implement new bioinformatic and computational tools to capture key biological parameters such as pathway analysis, data integration with visualization, and integrated cancer biology;
• Develop pipeline and network-wide quality control methods for the system developed as a response to the goals stated above; and
• Process/integrate analytical data from other components of network to generate disease level findings and interpretations as well as cross-disease analyses.
• These goals will necessitate continuous communication and interactions among the members of the network. Each member of the GDAC group will have distinct functions and capabilities and be responsible for individual analytical components.

Interactions of GDACs with other members of the network. All GDAC awardees, including the Processing GDAC to be supported under this FOA, must be able to accommodate their activities in the general scheme of the coordinated interactions across the various resources as outlined below.

• Biospecimen Core Resource (BCR): The BCR serves as the tissue processing center and provides the molecular biomolecules for all CCG-approved projects. Standard operating procedures are used for clinical data collection, sample collection, pathological examination, biomolecule (e.g., DNA and RNA) extractions, quality control, laboratory data collection, and biomolecule distribution to the Cancer Genome Characterization Centers. The samples are required to have patient informed consent for the public release of data or an IRB waiver.
• Genome Characterization Centers (GCCs): GCCs conduct high-throughput comprehensive genome-wide analyses using validated technologies (e.g., gene expression profiling, detection of chromosomal segment copy numbers alteration) to reveal the spectrum of genomic changes that exist in human tumors and to identify genomic regions for further characterization. The data generated by the characterization centers will be the main (but not only) starting point for the analyses performed by the GDACs.
• Genomic Data Analysis Network (GDAN): The aggregated capabilities of the awardees from the present FOA and its companions (RFA-CA-15-019 and RFA-CA-15-020) will produce the bulk of the analysis required to interpret the data generated by the GCCs described above. This group will work closely and collaboratively with all other components of the pipeline and be responsive to the necessities of the analysis requests posed by the AWGs that will be formed for each CCG-approved project.
• Data Management, Storage and Public Access: The whole of the data generated by CCG-approved projects is presented to the scientific community though publically-available databases that contain not only the raw data and associated metadata, but all of the analysis files generated in the course of each project. At the time of this FOA, that task is performed by the DCC (through project-specific data portals) and CGHub. In the near future, these activities will be consolidated under a single entity, the GDC, where all members of the network will deposit their data.

Required Team Expertise. Each GDAC applicant team must have current expertise in computational data analysis and genomics-specific bioinformatics as well as clinical oncology and/or cancer biology. GDACs would benefit greatly by being jointly led by two investigators: (i) an expert in bioinformatics/computation and (ii) either a clinical oncologist or a cancer biologist who can help to guide the analyses and contribute to the interpretation of the results at the disease-level.

GDACs differ by the proportion of the effort devoted to the development of novel analyses, but each GDAC will be required to develop novel approaches to data analysis and data integration. The analytical pipelines will be available as a resource to the scientific community for data integration and for advanced translational evaluation of genomic data. The analytical pipelines may result in valid conclusions which are not 100% concordant due to the different analytical methods used. The GDACs will need to develop annotation which will be made available along with the pipeline to explain any differences in data interpretation to the research community.

Specific Objectives for Processing GDAC. The proposed Processing GDAC must have all the expertise, personnel, instrumentation and throughput capabilities that will be required for the objectives defined below (with additional specific details in Section IV, under "Research Strategy".)

• Objective 1: Development of innovative bioinformatics and computational tools and methodologies (requires drawing clinical and biological correlations).
• Objective 2: Conducting integrative analysis of data sets generated by GCCs using the bioinformatics tools developed by each GDAC.

Objective 3: Implementing an integrative bioinformatics approach utilizing existing bioinformatic tools for timely high-throughput processing and analyses of genome-wide data.

• Data Sharing Requirements for GDACs:

Public availability of data/information generated by all genomics data resulting from NCI-supported initiatives will be critical to facilitate disease-relevant discoveries of clinical significance and is a goal of this initiative. Therefore, sharing as a public resource all rigorously validated data resulting from GDACs is essential for this initiative. For details, see Section IV.2, under "Resource Sharing Plan".

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:

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

Nonprofits Other Than Institutions of Higher Education

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

For-Profit Organizations

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

Governments

• State Governments
• County Governments
• Eligible Agencies of the Federal Government
• U.S. Territory or Possession

Other

• Non-domestic (non-U.S.) Entities (Foreign Institutions)

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

Applicant Organizations

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

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

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

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

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

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

GDAC applicants are strongly encouraged to take advantage of the multiple PDs/PIs option. For example, the proposed GDACs may include one PD/PI with primary expertise in bioinformatics and another PD/PI with primary experience in cancer biology or clinical oncology.

There is no limit on the number of applications a single institution can provide to this FOA or its companions (RFA-CA-15-019 & RFA-CA-15-020), as long the PD/PI of record in each application is a different person. No PD/PI can apply to more than one GDAC type.

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 and each is led by a different PI/PD.

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).

Applicants must download the SF424 (R&R) application package associated with this funding opportunity using the Apply for Grant Electronically button in this FOA or following the directions provided at Grants.gov.

It is critical that applicants follow the 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:

Jean C. ZenKlusen, Ph.D
Director
The Cancer Genome Atlas
Center for Cancer Genomics
National Cancer Institute
Telephone: 301-451-2144
Fax: 301-480-0969
Email: [email protected]

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

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

Each GDAC applicant team must have current expertise in computational data analysis and genomics-specific bioinformatics as well as clinical oncology and/or cancer biology. Accordingly,

GDAC applicants are strongly encouraged to take advantage of the multiple PDs/PIs option. For example, the proposed GDACs may include one PD/PI with primary expertise in bioinformatics and another PD/PI with primary experience in cancer biology or clinical oncology.

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

Leadership Effort Commitment: The contact PD/PI must commit and maintain through the life of the award a minimum of 2.4 person-month of effort. For other PDs/PIs (if designated), a minimum effort of 1.2 person-month per PD/PI is required.

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: Define Specific Aims of the proposed Processing GDAC. The proposed aims must be consistent with achieving the required objectives.

Research Strategy: Use standard sections (Significance, Innovation, and Approach), address all the objectives and specific requirements defined below.

Overall GDAC Profile: Explain how the proposed Processing GDAC will ensure that the research team can develop appropriate approaches for massive processing of genomic data, actually process large quantities of such data, and generate integrated results and/or higher-level interpretations of the genomic patterns. The goal must be to ensure that all anticipated research outcomes are of quality, rigor, and novelty enabling the cancer research community to develop a new generation of studies that would leverage cancer genomics for the benefit of cancer patients. (Note, however, that the actual conduct of translational and/or functional studies that follow-up on genomics findings are out of scope for this FOA.)

GDAC Objective 1: Development of innovative bioinformatics and computational tools and methodologies (requires drawing clinical and biological correlations). In addressing this objective, provide sufficient details to document that your plans are consistent with the following Requirements for Objective 1:

• Tools should be targeted for the evaluation of data sets from genomics projects (to include clinical data), capable of analyzing these data sets in a standardized fashion.
• The analytic pipeline needs to be flexible to be able to analyze data for each tumor type and across different tumor types.
• Existing tools may include systems biology approaches, data integration with visualization, integrated pathway analysis methods or other approaches that increase the ability to interpret genomic data at the biologically and clinically relevant levels.
• Novel tool development may be proposed to functionally integrate or link existing tools or types of output, however, tool development is not the primary goal of this FOA.
• Tools should be automated to the extent that one does not require a degree in bioinformatics or computer science to perform an analysis. Tools should be user-friendly and designed so that researchers can replicate the analyses using their own datasets.
• Each GDAC should develop a user manual, which will be disseminated through the DCC.

GDAC Objective 2: Conduct Integrative analysis of data sets generated by GCCs using the bioinformatics tools developed by each GDAC. In addressing this objective, provide sufficient details to document that your plans are consistent with the following Requirements for Objective 2:

• Each GDAC will analyze and integrate data generated by the GCCs and/or other network components, and integrated by the Processing GDACs to identify the complex pattern of changes that occur in the cancer cases studied.
• Data to analyze will include the comprehensive detection of genomic, epigenomic and transcriptomic aberrations, including: alterations in DNA segment copy numbers, translocations, loss of heterozygosity, altered epigenetic patterns, changes in gene expression, mutations, or other genomic-level data.
• Each GDAC will support the Analysis Working Groups that will be formed for each project and provide high-quality results that are interpretable by a non-bioinformatics specialist.
• It is expected that GDACs performing genomic analysis will be continuously improving their analytical methods to enhance the output from genomic data and working toward the goal of automated data analysis. These improvements could include optimization of sensitivity and resolution in the detection of cancer associated genomic and/or epigenomic and/or transcriptome alterations, with specific emphasis on enhancing analysis throughput.

GDAC Objective 3: Implement an integrative bioinformatics approach utilizing existing bioinformatic tools for timely high-throughput processing and analyses of genome-wide data. Awardees for this type of GDAC will be required to develop appropriate "design document" during the award. In addressing this objective, applicants must outline in sufficient details their plans for this objective. The plans must be consistent with the following Requirements for Objective 3:

• A pipeline design must allow for the creation of a system that is capable of integrating omics data generated from CCG approved projects using existing, state of the art tools and in high-through-put fashion. A workflow that describes each element of the pipeline, as well as quality control measures should be included.
• The design outline must specify how each type and level of data will be integrated as appropriate (see https://tcga-data.nci.nih.gov/tcga/tcgaDataType.jsp for a description of levels 1 through 4 and examples of types of TCGA data).
• Provide a timeline for completing the design document, developing the pipeline, and describe the resources and collaborations required to build the pipeline. This timeline must be consistent with the expectation that Processing GDACs should be able to produce a functional pipeline that is capable of performing the integrative analyses by the end of the first six months of project period.
• Applicants for Processing GDACs should propose a plan for how the fully implemented and automated systems generated by Processing GDACs will be maintained beyond the five-year funding period, and define the packaging method to be used to ensure portability of the pipeline with no dependencies to the GDAC home institution.
• The overall system design should enable and facilitate generation of disease-relevant conclusions for the various types of cancer by integrating data for downstream analysis by other components of the GDACs. The resulting system should be capable of providing data in standardized formats for further analyses.
• The overall pipeline and individual tools should be automated and include user interface(s) appropriate for scientists who are not necessarily experts in bioinformatics and computer science.
• The pipeline will need to be flexible and efficient so that data analysis can occur in real time .
• Tool development, integration of results and report generation could occur simultaneously or in succession depending on the requirements of the data set being analyzed.
• Plans should include the provision that once the pipeline is established, each GDAC will develop a user manual, which will be disseminated through the data portal.

Interactions across GDACs (Optional):

Applicants may outline their perspective/suggestions on how the future GDAC awardees would interact to maximize the benefits for the stated programmatic goals.

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.
• Data Sharing Plans must be consistent with NIH data sharing guidelines and the data sharing procedures developed by Genomic Data Sharing Committee (http://gds.nih.gov/03policy2.html)
• The plan must also be consistent with the goals and requirements of this FOA, including the following aspects:
• GDAC awardees will be required to use an appropriate NCI-supported central data repository. This role will be served by the Data Coordinating Center (DCC) and Cancer Genomics Hub (CGHub) and later by the Genomic Data Commons (GDC). GDAC awardees are expected to adapt their submission pipelines as necessary to accommodate this transition.
• Data Sharing Plan should indicate how and when GDAC data will be released and shared through the appropriate central repository mentioned.
• Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.

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.

When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. 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.

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. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.

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.

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

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

Applicants are required to follow the instructions for post-submission materials, as described in NOT-OD-13-030.

Important Update: See NOT-OD-16-006 for updated review language for applications for due dates on or after January 25, 2016.

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.

The emphasis of this FOA is on the ability of the research team to process large quantities of genomic data and create integrated results and/or higher-level interpretations of the genomic patterns. These anticipated research outcomes should be of quality, rigor, and novelty enabling the cancer research community to develop a new generation of studies that would leverage cancer genomics for the benefit of cancer patients.

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 project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?

Specific to this FOA: How appropriate are the technologies proposed for genome-wide detection of the types of molecular aberrations that are known to be implicated in the development and progression of a broad range of cancer types? How well does the application demonstrate adequate commitment to state of the art technology or analytical pipeline improvements?

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

Specific to this FOA: How strong is the applicant team in terms of expertise in computational systems biology and pathway mapping capabilities? What is the quality of the applicants' plan for bringing collaborators and resources together to accomplish the goals of the FOA?

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

Specific to this FOA: What is the likelihood for potential innovation in the proposed improvements in genomic methods including data dissemination, throughput or cost?

Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed?

Specific to this FOA: How well are the approaches for level 1-4 data analysis and quality control measures optimal to yield reliable data? How logical and implementable are the plans for using high-throughput technologies, assimilating new technological developments and assuring quality control? How convincing is evidence provided to indicate that the applicant team can reach the specified initial minimum rate of sample analysis during the first 3 months of the project and increase the rate during the project period as required? How adequate are the informatics capabilities for the needs of the project? How sufficient are the plans in terms of the integration of technological advancements as they become available and validated for high throughput production?

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

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

Specific to this FOA: Does the proposed plan ensure the integration with other GCCs, GDACs and other components of the CCG pipeline?

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 five points: 1) proposed use of the animals, and species, strains, ages, sex, and numbers to be used; 2) justifications for the use of animals and for the appropriateness of the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures for limiting discomfort, distress, pain and injury to that which is unavoidable in the conduct of scientifically sound research including the use of analgesic, anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and 5) methods of euthanasia and reason for selection if not consistent with the AVMA Guidelines on Euthanasia. 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 Wide Association Studies (GWAS) /Genomic Data Sharing Plan.

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 National Cancer Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.

As part of the scientific peer review, all applications:

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

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

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

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

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.

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.

Cooperative Agreement Terms and Conditions of Award

The following special terms of award are in addition to, and not in lieu of, otherwise applicable OMB administrative guidelines, HHS grant administration regulations at 45 CFR Parts 74 and 92 (Part 92 is applicable when State and local Governments are eligible to apply), and other HHS, PHS, and NIH grant administration policies.

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

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

The PD/PIs will have primary responsibility for defining the specifics of the projects within the guidelines of this FOA and for performing all scientific activities. The PD/PIs must accept the close coordination of various aspects of scientific and technical management of the project by the Steering Committee and the NCI Project Scientists (outlined in the sections below).

The Principal Investigators will have the primary responsibility for:

• Defining research plan and goals, determining experimental approaches, and setting project milestones;
• Overseeing/performing the scientific activities of the plan, including: research design and protocol development, conducting experiments, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and preparation of publications;
• Committing and maintaining throughout the life of the award a minimum of 2.4 person-months of effort per year for investigator designated as the contact PD/PI. For other PD(s)/PI(s), a minimum of 1.2 person-months of effort per year is required.
• Monitoring the completion of established goals and benchmarks within the timeframe and budget proposed;
• As needed the PD/PIs will propose the validation of an improved method and its application for the project goals;
• Interacting and cooperating with NCI programmatic, technical, and administrative staff.
• Adhering to and implementing the decisions of each NCI Program Steering Committee.
• Overseeing and monitoring the process of data sharing;
• The lead PD/PIs will be responsible for the overall coordination of project activities scientifically and administratively at the awardee institution as well as any and collaborating institutions.
• Providing goals for throughput, quality, and cost for the proposed method of sample analysis to each NCI Program Steering Committee (as requested by the Program Office);
• Working on significant technology improvements (including a switch to another technology platform, if needed);
• Providing analytical approaches and statistical analysis support to analysis working groups (as requested by the Program Office)
• Conducting integrative data analyses to yield meaningful and disease-relevant interpretations;
• Submitting data to the DCC for quality assessment in any manner specified by the Program Office;
• Sharing and disseminating data on a schedule established by the Program Office as appropriate;
• Contributing to the integration of the data, analysis results and conclusions at the level of the entire genomic programs (i.e., working closely with investigators from other

GCCs/GDACs and NCI program staff);

• Accepting and implementing any other common guidelines and procedures approved the Program Office;
• Participating in the activities of the Research Network and attending its meetings.

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 HHS, PHS, and NIH policies.

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

A NCI Program Director(s) (acting as a Project Scientist(s)) will have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below. These NCI Staff Members will provide substantial input in terms of overall program coordination and directions.

Additional NIH staff members (e.g., from the NCI Center for Biomedical Informatics and Information Technology, NCI CBIIT) may also have substantial involvement in the role of Project Coordinators.

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

The NCI Project Scientist will:

• Participate with the other Program Office members in the group process of setting research priorities, deciding optimal research approaches and protocol designs, and contributing to the adjustment of research protocols or approaches as warranted; the Project Scientist will assist and facilitate the group process but not direct it;
• As appropriate, serve as a liaison between the awardees and the National Cancer Advisory Board, and the larger scientific community;
• Serve as a liaison between the GDAC awardees and other researchers engaged in cancer sample characterization, including: (a) other participants in genomic programs; and (b) those awardees involved in related NCI programs, and those within the international cancer research community;
• Periodically report progress of genomic programs to specific audiences at the NIH as required;
• Provide advice in the management and technical performance of the investigations;
• Assist in promoting the availability of the characterization data and related resources developed during the course of the genomic programs to the scientific community at large;
• Participate in data analyses, interpretations, and where appropriate, co-authorship of the publication of results of studies conducted through the various genomic programs;
• Assist awardees in the development (if needed) of policies for dealing with situations that require coordinated action within the genomic programs framework;

The NIH reserves the right to suspend or reduce the award of those project participants who fail to share and disseminate data on a schedule established by the Program Office or who are judged by the Program Office to make insufficient progress in technology improvements.

Areas of Joint Responsibility include:

CCG Research Network Steering Committee. CCG Research Network Steering Committee will serve as the main governing body of the various genomic programs, including: all awardees of the CCG Research Network funded by the NCI (i.e., the GCCs and GDACs). It is anticipated that the CCG Research Network Steering Committee will provide strategic coordination for all activities of the Network.

CCG Research Network Steering Committee will be composed of the following voting members: (a) the NCI Project Scientists (one or more); (b) one designated representative (lead PD/PI or designee of each of the awarded cooperative agreement GDACs and (c) the PD/PIs of each of the NCI-funded Genome Characterization Centers, and other Network components as deemed appropriate.

Each full member representing awardees will have one vote.

If there is more than one project scientist from the NCI, they will have collectively one vote.

The CCG Research Network Steering Committee Chair will not be an NIH staff member.

The CCG Research Network Steering Committee may establish sub-committees, as it deems appropriate. The NIH Project Scientists will serve on sub-committees, as they deem appropriate.

The CCG Research Network Steering Committee may, when it deems it to be necessary, invite additional, non-voting science advisors to the meetings.

These additional non-voting members may include, for example, representatives from the NCI Center for Bioinformatics and/or from a BCR, and/or Tissue Source Sites. Other NIH staff members may be requested to attend the CCG Research Network Steering Committee meetings if their expertise is required for specific discussions.

GDAC awardees (as well as other voting members of the CCG Research Network Steering Committee) will be required to accept and implement policies approved by the entire CCG Research Network Steering Committee. It is anticipated that decisions for all appropriate activities will be reached by a consensus of CCG Research Network Steering Committee and that NCI program staff will provide the input throughput this process. NCI retain rights to final approval of strategic decisions pertaining to the directions of the CCG Research Network.

The activities of the CCG Research Network Steering Committee will include the following:

Discussing progress in meeting the goals of CCG Research Network including all components of the Network;

Developing pilot experiments and undertaking other activities as required to meet the goals of the project.

Deliberating on specific operational and scientific issues to arrive at solutions to problems and recommend alterations in Network processes, policies, etc.

Developing recommendations for uniform procedures and policies necessary to meet the goals of CCG Projects (e.g., guidelines for data quality measures and assessment, conventions for data deposition, or recommendations for cost and throughput goals associated with the analyses);

Serving as a venue for coordination on the improvement of cancer genome characterization and analysis (e.g., through the dissemination of best practices and collective evaluation of new procedures, resources, and technologies);

Participating in conference calls and meetings for network investigators;

Preparing action items from the CCG Research Network Steering Committee meetings and deliver these to the entire committee within 30 days of each meeting.

Dispute Resolution Process:

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

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

A final progress 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 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.

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

eRA Commons Help Desk (Questions regarding 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 CenterTelephone: 800-518-4726
Web ticketing system: https://grants-portal.psc.gov/ContactUs.aspx
Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-710-0267

Jean C. ZenKlusen, PhD
National Cancer Institute (NCI)
Telephone: 301-451-2144
Email: [email protected]

NCI Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]

Amy R. Bartosch
Phone: 240-276-6912
[email protected]

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

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