NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC)

NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) is sponsored by National Institutes of Health (NIH). This Funding Opportunity Announcement (FOA) supports the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC).

Expired RFA-CA-15-023: Proteogenomic Data Analysis Centers for Clinical Proteomic Tumor Analysis Consortium (U24) This notice has expired. Check the NIH Guide for active opportunities and notices. Department of Health and Human Services Part 1.

Overview Information Participating Organization(s) National Institutes of Health ( NIH ) of Participating Organizations National Cancer Institute ( NCI ) Funding Opportunity Title Proteogenomic Data Analysis Centers for Clinical Proteomic Tumor Analysis Consortium (U24) U 24 Resource-Related Research Projects Cooperative April 5, 2021 - This RFA has been reissued as RFA-CA-21-024 .

NOT-OD-16-004 - NIH & AHRQ Announce Upcoming Changes to Policies, Instructions and Forms for 2016 Grant Applications NOT-OD-16-006 - Simplification of the Vertebrate Animals Section of NIH Grant Applications and Contract Proposals November 16, 2015 - Notice of Pre-application Webinar for Clinical Proteomic Tumor Analysis Consortium. See Notice NOT-CA-15-044 .

Funding Opportunity Announcement (FOA) Number Companion Funding Opportunity RFA-CA-15-021 , U24 Resource-Related Research Project - Cooperative Agreements RFA-CA-15-022 , U01 Research Project - Cooperative Agreements Additional Information on Eligibility .

Catalog of Federal Domestic Assistance (CFDA) Number(s) Funding Opportunity Purpose This Funding Opportunity Announcement (FOA) is a part of the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC). This reissuance of the CPTAC program leverages recent advancements in cancer proteomics and genomics and accelerates research in these areas by disseminating research resources for the scientific community.

The program will support broad efforts focused on several cancer types to explore further the complexities of cancer proteomes and their connections to abnormalities in cancer genomes.

The potential of proteomic and proteo-genomic approaches will also be explored in translational research focused on clinically-relevant problems, such as the ability to predict which treatments are likely to be effective against a specific patient's tumor.

This FOA solicits applications for multidisciplinary Proteogenomic Data Analysis Centers (PGDACs), which will provide data analysis and biological and clinical interpretation of CPTAC data. PGDAC awardees will be expected to develop computational tools for data analysis, data integration, and visualization and apply these tools to CPTAC data.

PGDACs will interact with additional CPTAC sub-programs Proteome Characterization Centers (PCCs, to be supported by RFA-CA-15-021) that will use various standardized proteomic analysis technologies for the systematic and comprehensive proteome-wide characterization of defined sets of genomically-characterized samples.

These samples (human biospecimens, cultured cells, and animal cancer models) will be provided by the NCI; and Proteogenomic Translational Research Centers (PTRCs, to be supported under RFA-CA-15-022) that will apply state-of-the-art proteomic and proteo-genomic approaches to elucidate responses to cancer therapeutic agents, e.g., in order to predict which therapeutic agents are likely to be effective against a specific patient's tumor.

Open Date (Earliest Submission Date) Letter of Intent Due Date(s) 30 days prior to application due date January 27, 2016, by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on this date. No late applications will be accepted for this Funding Opportunity Announcement.

Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission AIDS Application Due Date(s) Required Application Instructions It is critical that applicants follow the instructions in (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 I. Funding Opportunity Description Section II. Award Information Section III.

Eligibility Information Section IV. Application and Submission Section V. Application Review Information Section VI.

Award Administration Information Section VII. Agency Contacts Section VIII. Other Information Full Text of Announcement Section I.

Funding Opportunity Description This Funding Opportunity Announcement (FOA) is a part of the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC). This reissuance of the CPTAC program leverages recent advancements in cancer proteomics and genomics and accelerates research in these areas by disseminating research resources for the scientific community.

The program will support broad efforts focused on several cancer types to explore further the complexities of cancer proteomes and their connections to abnormalities in cancer genomes. The potential of proteomic and proteo-genomic approaches will also be explored in translational research focused on clinically-relevant problems.

This FOA solicits applications for multidisciplinary Proteogenomic Data Analysis Centers (PGDACs), which will provide data analysis and biological and clinical interpretation of CPTAC data. PGDAC awardees will be expected to develop computational tools for data analysis, data integration, and visualization and apply these tools to CPTAC data.

The tools and approaches to be proposed for PGDACs should be suitable for analyses and meaningful interpretations of data derived from diverse types of samples (such as clinical specimens, cultured cells, animal models of human cancers, etc.).

PGDACs will interact with additional CPTAC sub-programs that Proteome Characterization Centers (PCCs, to be supported under RFA-CA-15-021) that will use various standardized proteomic analysis technologies for the systematic and comprehensive proteome-wide characterization of defined sets of genomically-characterized samples.

These samples (human biospecimens, cultured cells, and animal cancer models) will be provided by the Proteogenomic Translational Research Centers (PTRCs, to be supported under RFA-CA-15-022) that will apply state-of-the-art proteomic and proteo-genomic approaches to elucidate responses to cancer therapeutic agents, e.g., in order to predict which therapeutic agents are likely to be effective against a specific patient's tumor.

This FOA is open to all qualified applicants regardless of whether or not they participated in the previous issuance of the program. This unique combination of coordinating research approaches, sharing of research data, and combining proteomic with genomic analysis, should allow the CPTAC program to produce a more unified understanding of cancer biology with translational potential.

In addition, data and resources (assays) are to be made publicly available to the research community through CPTAC's Data Coordinating Center (DCC), Assay Portal, and other portals to maximize utility and public benefit. These open community resources and knowledge are expected to lead to novel translational approaches and, ultimately, to accelerate the development of new cancer diagnostic, prevention, and treatment strategies.

The following key terms are used in the FOA as defined proteomics " refers to the comprehensive characterizations and analyses of proteins and their derivatives translated from a cancer genome using a human biospecimen or a preclinical model (cultured cell or animal model). The proteomics " refers to the "untargeted and unbiased" identification and quantification of a maximal number of proteins in a biological or clinical sample.

The term targeted proteomics refers to the quantitative measurements focused on a defined subset of total proteins in a biological or clinical sample.

proteogenomics" denotes the intersection of cancer proteomics and genomics and, specifically, understanding how various distinct changes at the proteome level are related to abnormalities in cancer genomes and/or changes at the functional level (i.e., in gene expression), while protein information helps improve and refine cancer genome annotation.

In the context of this FOA, particularly important is the potential of proteogenomic approaches to better explain cancer complexities than genomics or proteomics For the CPTAC program, the term "comprehensive proteomic characterizations" means the generation of proteome-wide experimental data using human specimens/model samples, whereas "proteomic/proteogenomic data analysis" refers to the use of bioinformatic approaches and computation tools to analyze the primary data in various ways and in conjunction with other available complementary data, aiming to achieve higher levels of data/pathways/concepts integration.

Three levels of data analysis are envisioned below: o Discovery Proteomics Research - Analysis of raw experimental data to generate results on peptide/protein identification and quantitation, post-translational modifications (PTMs) identification, site localization and quantitation using a reference genome; o Targeted Proteomics Research - Analysis of raw experimental data to generate quantitative results on peptide/protein concentrations of the selected targets from Discovery Proteomics Research .

genome-proteome data at the linear sequence level (DNA, RNA, peptides/proteins with relative quantitation obtained from Discovery Proteomics Research using personalized genomic data).

visualization and analysis of omics data mapped onto networks and pathways Despite significant progress in understanding cancer at the molecular level, the complexity that comprises this disease remains a daunting barrier to developing interventions that are needed to diagnose, treat and prevent cancer in the era of precision medicine.

Vital to the progress in these areas are the discovery and understanding of cancer-specific aberrations at various molecular and cellular levels. Although proteins reflecting the genomic changes in cancer have the potential to become clinically meaningful molecular markers, their discovery and confirmation for clinical use have proven to be extremely challenging.

In the past decade, cancer researchers have made significant progress in identifying a new molecular taxonomy of cancer through the use of genomics.

This FOA aims to leverage the investments in cancer genomics by building on the achievements in cancer proteomics in order to accelerate molecularly-oriented cancer research toward basic discovery and The CPTAC program (RFA-CA-07-012) began in 2006 as a part of the Clinical Proteomic Technologies for Cancer initiative at the NCI, the purpose of which was to understand and address the experimental and analytical sources of error in existing proteomics technologies, in order to complement genomic and transcriptomic analyses used to improve diagnostics, therapeutics, and prevention for cancer.

Program highlights include the standardization of mass spectrometry (MS) methodologies for untargeted protein analyses (discovery proteomics), standardization of multiple reaction monitoring (MRM) mass spectrometry in targeted protein analyses (targeted proteomics), adoption of a MRM assay for thyroglobulin by clinical reference laboratories, development of an open-source computational tool (Skyline) for designing MRM assays that is supported by major instrument vendors, development of mock 510(k) device clearance documents using targeted proteomic platforms in coordination with the Food and Drug Administration (FDA) and the American Association for Clinical Chemistry (AACC), and development of open data sharing policies in proteomics that are supported by peer-reviewed journals.

To begin to apply these outputs, the second phase of CPTAC was initiated in 2011 (RFA-CA-10-016) as a pilot collaborative network to utilize the CPTAC’s state-of-the-art standardized proteomic workflows to study genomically-characterized tumors (such as those from The Cancer Genome Atlas (TCGA) and others) to add an additional layer of biology to cancer.

The goal was to apply deep proteomic analysis to tumors that have undergone comprehensive genomic characterization, to gain additional biological insights that would have been difficult or impossible to obtain solely through genomics. All data and analytical tools were made broadly available to the research community through public databases (CPTAC's Research Resources: Data Portal, https://cptac-data-portal. georgetown.

edu/cptacPublic ; Assay Portal, https://assays. cancer. gov ; Antibody Portal, http://antibodies.

cancer. gov ), in order to democratize proteomics science. The current CPTAC program is composed of Proteome Characterization Centers (PCCs) with expertise in proteomics, genomics, cancer biology, oncology and clinical chemistry that perform coordinated research projects to comprehensively characterize and analyze cancer specimens selected for study.

PCCs have interrogated three cancer types (colorectal, ovarian and breast tumors), while successfully demonstrating the scientific benefits of integrating proteomic research with genomics to produce a more unified understanding of cancer biology, while creating open community resources that are widely used by the cancer community.

Such an integrated proteogenomics approach is now bringing key insights into genomic abnormalities manifested at the protein network and pathway level. Overall CPTAC Structure and Functions The CPTAC program will consist of the following sub-programs: Characterization Centers (PCCs).

To improve the molecular understanding of cancer biology, PCC awards (RFA-15-021) will comprehensively characterize the proteomic composition of human biospecimens and preclinical models (to be provided by the NCI). PCC teams will provide experimental raw data and metadata to the Data Coordinating Center (see below), and coordinate data analysis activities with PGDACs. Translational Research Centers (PTRCs).

To complement the comprehensive approaches of the PCCs, PTRC awards (RFA-15-022) will address clinical questions of drug response/toxicity prediction and resistance. PTRCs will include well-conceived translational and/or clinical questions, access to appropriate clinical trial biospecimens (tumors), state-of-the-art proteomic capability, and a proteogenomic-based research approach.

Research would support cancer research model studies (comprehensive proteogenomic discovery research), clinical trial sample acquisition, followed by targeted assay development and application on clinical trial samples. PTRCs will provide experimental raw data, metadata and preliminary analysis results to the Data Coordinating Center (see below), and coordinate data analysis activities with PGDACs.

Data Analysis Centers (PGDACs, covered by this FOA). In collaboration with PCCs and PTRCs, PGDAC awards will support innovative bioinformatics development and application to integrate data analyses across the entire proteome and genome.

PGDACs are to assist researchers (PCCs, and PTRCs accordingly) to integrate, visualize and analyze the data at linear sequence, network and pathway level, including PTMs of proteins and protein-protein interactions.

resources (supported by the NCI beyond the scope of this FOA) available to To facilitate the activities of individual PGDACs and other research components of the CPTAC program, the NCI has created and directly supports additional resources beyond the scope of this FOA. These resources Source Sites (TSS), which collect human biospecimens and clinical data.

Core Resource (BCR) that serves as a centralized laboratory(s) that receives, processes, qualifies, and distributes treatment-na ve tumor and matched normal control human biospecimens to the PCCs.

The BCR serves as the interface between the CPTAC program and the TSSs collecting, ensuring and verifying that CPTAC human subjects protections and guidelines are adhered to and that all regulations are followed at each TSS, including use of language consistent with the CPTAC informed consent documents. Note: only PCC awardees will receive NCI-collected specimens .

Characterization Center (GCC) that will genomically characterize NCI-provided CPTAC biospecimens to be characterized and analyzed by the PCCs. Data Resource (CDR) that will receive, qualify, store, and distribute clinical Management System (QMS). The QMS works with all CPTAC awardees to define quality processes and metrics, and to track nonconforming events.

Coordinating Center (DCC): All CPTAC awardees will have to use DCC as the repository for their data, protocols, tools, etc. DCC serves as the hub and central repository of all data, and facilitates the transfer of data between the Centers and quality control of data.

The DCC will also implement the CPTAC common data analysis pipeline, consisting of quality control metrics applied to genomic and proteomic data and peptide/protein identification and quantification for proteomic data. Resources . The CPTAC program currently has three dedicated public resources for disseminating its research findings.

Applicants are encouraged to consider using the items in these portals, as appropriate. These resources Portal ( https://cptac-data-portal. georgetown.

edu/cptacPublic ), which serves as a centralized repository for the dissemination of proteomic data collected by the CPTAC program. Portal ( https://assays. cancer.

gov ), which serves as a public repository of well-characterized, targeted proteomic assays. The Assay Portal contains analytically validated assays and standard operating procedures (SOPs) that can be used to compare results across the board. Assays in the portal adhere to Fit-for-Purpose validation guidelines distinguished by their performance and extent of analytical characterization (Tiers 1-3).

( http://proteomics. cancer. gov/newsevents/newsannouncements/archive/2013/standardstargeted ).

Portal ( http://antibodies. cancer. gov ), which serves as a community resource of unbiased renewable antibodies (monoclonal) with all associated SOPs and characterization data made publicly available to the research community.

informatics tools ( http://proteomics. cancer. gov/resources/softwaretools ).

Various informatics tools (developed or refined by CPTAC investigators) are available (e.g., for analytical metric quality control, along with data visualization, analysis and integration of cancer-relevant networks and pathways, etc.).

research resources : Applicants for one or more of the CPTAC sub-programs are encouraged to consider establishing partnerships with other groups, and divisions and programs within NCI that may benefit the overall program goals. For example, the awardees could take advantage of the TCGA ( http://cancergenome. nih.

gov ), Cancer Target Discovery and Development Network (CTD2; http://ocg. cancer. gov/programs/ctd2 ), Early Detection Research Network (EDRN, http://edrn.

nci. nih. gov ), the Cancer Diagnosis Program (CDP, http://www.

cancerdiagnosis. nci. nih.

gov ), and Cancer Therapy Evaluation Program (CTEP, http://ctep. cancer. gov ) including the National Clinical Trials Network (NCTN) and Experimental Therapeutics Clinical Trials Network (ET-CTN), and databases of clinical studies of human participants such as publicly supported clinical trials around the world ( https://clinicaltrials.

gov). Research Objectives and Main Requirements for this FOA PGDACs will participate in one or more of the following activities: computational tool development, data analysis, data integration, and data visualization. These activities may use as input any and all levels of CPTAC data, from instrument files to protein/gene identifications to clinical data.

PGDAC research aims may span a range of topics, including, but not limited to: cancer biology, clinical diagnostics/therapeutics, quality control, and/or novel computation. The goal is that the aggregate analysis from all PGDACs will provide a comprehensive analysis of CPTAC data.

Each PGDAC will be expected to apply its style of analysis to the data generated by the PCCs (collected for 5-6 human tumor types using NCI-provided biospecimens) as well as data generated by: NCI's Human Cancer Model Initiative, Patient-Derived Xenograft (PDX) Repository, and the PTRCs. Note.

Human biospecimens (primary emphasis of this FOA) and preclinical models (cell lines and patient-derived xenografts) will be provided by the NCI to the PCCs. PGDACs are expected to analyze PCC data on this Human biospecimens (treatment-na ve tumor, accompanied by adjacent normal tissue when available), will be prospectively collected using standardized protocols optimized for proteomics-based measurement technologies.

Biospecimens are to include well-annotated clinical data and undergo genomic characterization (anticipated analyses are whole exome sequencing; RNA sequencing; genotyping and DNA copy number).

Biospecimens will be from a selection of cancer types, potentially including glioblastoma multiforme (GBM), lung adenocarcinoma, lung squamous cell carcinoma, pancreatic ductal adenocarcinoma, clear cell kidney carcinoma, cutaneous melanoma, head and neck squamous cell carcinoma, sarcomas, uterine corpus endometrial carcinoma, and acute myeloid leukemia (AML).

Anticipated are 200 cases (tumor with adjacent normal) for each cancer type, with 100 cases to be used in the Discovery Research Arm and 100 cases in the Confirmatory Research Arm . The number of specimens will be sufficient to ensure appropriate statistical power. Additional information pertaining to the type of biospecimens to be provided by the NCI will be forthcoming.

PGDACs are expected to also collaborate with two NCI programs - NCI’s Human Cancer Model Initiative (cell lines) and Patient-Derived Xenograft (PDX) Repository program. Each PGDAC is expected to apply its data analysis tools to data generated by the PCCs from these preclinical samples (anticipated 1000 samples from each program for a total of 2000 samples).

To foster the development of collaboration among PCC, PTRC, and PGDAC applicants, a Teaming Website has been developed. Please visit and register at http://proteomics. cancer.

gov . Research Objective 1: Develop one or more computational tools to elucidate some aspects of the molecular complexity of cancer.

Tools may fall into one of the following categories: (1) new bioinformatics and computational tools to capture key biological parameters such as pathway analysis, data integration with visualization, and integrated cancer biology, (2) pipeline and network-wide quality control methods for the system, (3) processing or integration of analytical data from other sub-programs of CPTAC to generate disease level findings and interpretations.

These goals will necessitate continuous communication and interactions among the members of the CPTAC network. Each member of the PGDAC group will have distinct functions and capabilities and will be responsible for individual analytical pieces of the pipeline.

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 under analysis and current status of the computational capacity of the applicants. PGDAC tools should complement the analyses done by the DCC's Common Data Analysis Pipeline (CDAP).

The CDAP will use the reference genome to identify and quantify peptides/proteins and the genes from which they Research Objective 2: Apply computational tools to CPTAC data. PGDACs are expected to deploy computational tools on CPTAC-wide test data within six months of the award kick-off.

Data to analyze will include the comprehensive inventory of proteomic, genomic, epigenomic and transcriptomic aberrations, including: differential expression of proteins, somatic variation of protein sequence, alterations in DNA segment copy numbers, translocations, loss of heterozygosity, altered epigenetic patterns, changes in gene expression, mutations, or other CPTAC generated data.

Each PGDAC is to utilize integrative tools/methods with which to: (1) analyze Genome Characterization Center (GCC), PCC, PTRC and/or PGDAC generated data, (2) integrate CPTAC data (to include data and metadata derived from CPTAC biospecimens), and (3) identify potentially cancer-related molecular alterations.

These tools/methods should be applied to normalized data obtained from the molecular characterizations by GCCs, PCCs, or PTRCs, or to data If appropriate and desirable, PGDAC applicants are encouraged to develop custom tools for some types of analyses mentioned. Research Objective 3: Identify candidates for targeted protein assays CPTAC characterizations of specimens entail a Discovery Research Arm and a Confirmatory Research Arm .

The Discovery Research Arm will include unbiased characterization of all detectable protein forms in a sample using analytically validated proteomic discovery technologies. The Confirmatory Research Arm will include targeted multiplex proteomic assays against corresponding protein targets.

The prioritization of corresponding proteins/peptides of interest will be done in coordination with the PCCs and PTRCs, with final selection made by the Protein Candidate Selection Subcommittee and the Steering Committee (see below). The CPTAC Research Resource will facilitate the development and application of reference materials and key reagents for network studies if needed.

All characterization data will be made available to the PGDAC network, other units of the CPTAC program, and to the public through the CPTAC Effort Coordination with PCCs.

PCCs are expected to use various standardized proteomic analysis platforms and technologies to systematically and comprehensively characterize cancer proteomes that derive from genomic alterations and abnormalities in samples (predominantly tumors), as well as confirming discovered protein/peptide findings in a set of independent biospecimens.

Thus, the PCCs will coordinate and provide experimental raw, metadata and Level 1 (see Section IV. 2 below) analysis results to the DCC. The DCC will, in turn, perform proteomic analysis via a Common Data Analysis to ensure the quality of data prior to distributing the data to the PGDACs and others for integrative analyses and public data Effort Coordination with PTRCs.

PTRCs are expected to address clinical questions of drug response/toxicity prediction and resistance. PTRCs will provide experimental raw data, metadata and preliminary analysis results to the Data Coordinating Center, and coordinate data analysis activities with PGDACs. Bioinformatics teams in the PTRCs are required to conduct proteogenomic data analyses and contribute to the overall interpretation of the results.

However, all data produced by the PTRCs for transfer to the PGDACs are expected to enable more extensive and comprehensive integrative analyses to enhance deeper data visualization, analysis, and interpretation.

PTRCs will provide all data and analysis results to the CPTAC DCC where quality control and assurance of the data will be performed prior to distributing the data to the PGDACs and others for integrative analyses and releasing the data to the public (see Section IV). Governance of the NCI Clinical Proteomic Tumor Analysis The CPTAC program will be governed by CPTAC Steering Committee (SC).

The SC will oversee and coordinate the activities of all PCCs, PTRCs, and PGDACs. Details on the composition and functions of SC are provided in Section VI. Award Administration Information, Terms and Conditions of Cooperative Agreement, Areas of Joint Responsibility.

Evaluation of the Program PGDACs will be required to participate in an external evaluation process of the CPTAC program coordinated by NCI Program Staff. The purpose of the evaluation process is to monitor and assess the performance of the PGDACs in achieving the goals of this FOA.

Criteria for the evaluation part will be developed by NCI Program Staff in partnership with the CPTAC External Scientific Panel (ESP) (as described in Section VI). Section II. Award Information Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement.

Substantial involvement means that, after award, NIH scientific or program staff will assist, guide, coordinate, or participate in project activities. Application Types Allowed Glossary and the SF424 (R&R) Application Guide provide details on Funds Available and Anticipated Number of Awards The NCI intends to commit $4.

5 million in FY2016 to fund Future year amounts are anticipated to be at the same levels, but will ultimately depend on annual appropriations. Application budgets for each Center may not exceed $675,000 in direct costs per year and need to reflect the actual needs of the Applicants may request up to 5 years of support. 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 Nonprofits Other Than Institutions of Higher Education Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Nonprofits without 501(c)(3) IRS Status (Other than Institutions For-Profit Organizations (Other than Small Businesses) Eligible Agencies of the Federal Government U.S. Territory or Possession 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 Foreign components, as defined in the NIH Grants Policy Statement , are allowed. 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 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 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. 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.

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 must have an active DUNS number and SAM registration in order to complete the 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.

Eligible Individuals (Program Director/Principal 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 An investigator designated as a PD/PI on a PCC application in response to RFA-15-021 cannot be designated as a PD/PI under this FOA. However, these individuals can serve as key personnel within a PGDAC application.

This FOA does not require cost sharing as defined in the NIH Grants Policy Statement . 3. Additional Information on Eligibility Applicant organizations may submit more than one application, provided that each application is scientifically distinct.

The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will A new (A0) application that is submitted before issuance of the summary statement from the review of an overlapping new (A0) or resubmission 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 ). Section IV. Application and Submission Information 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 . 2. Content and Form of Application Submission It is critical that applicants follow the instructions in (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 For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant 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