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 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 Proteome Characterization Centers (PCCs). PCC awardees will be expected to work as an interactive group and 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.

PCCs will interact with additional CPTAC sub-programs that include:

• Proteogenomic Data Analysis Centers (PGDAC, to be supported by RFA-CA-15-023) that will conduct integrative analyses of data across the entire proteomes and genomes of cancer types of focus to elucidate how distinct changes at the proteome level are related to abnormalities in cancer genomes and/or changes at the functional level; 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.

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.

Key Definitions:

The following key terms are used in the FOA as defined below.

• "Cancer 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 term "discovery 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.
• "Cancer 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 alone.
• 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:
  
• Level 1:
• 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 (required under this FOA);
• Targeted Proteomics Research - Analysis of raw experimental data to generate quantitative results on peptide/protein concentrations of the selected targets from Discovery Proteomics Research.
• Level 2: Integration of genome-proteome data at the linear sequence level (DNA, RNA, peptides/proteins with relative quantitation obtained from Discovery Proteomics Research using personalized genomic data).
• Level 3: Integration, visualization and analysis of omics data mapped onto networks and pathways obtained from Discovery Proteomics Research.

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 clinical impact.

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 characterizations, to gain additional biological insights that would have been difficult or impossible to obtain solely through genomics approaches. 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.

The CPTAC program will consist of the following sub-programs:

• Proteome Characterization Centers (PCCs, covered by this FOA). To improve the molecular understanding of cancer biology, PCC awards 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.
• Proteogenomic 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.
• Proteogenomic Data Analysis Centers (PGDACs). In collaboration with the PCCs and the PTRCs, PGDAC awards (RFA-15-023) 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.

Additional resources (supported by the NCI beyond the scope of this FOA) available to CPTAC awardees:

To facilitate the activities of individual PCCs and other research sub-programs of the CPTAC program, additional NCI-supported resources beyond the scope of this FOA will be provided to awardees. These include:

• NCI-supported Biospecimen Resources:
• Tissue Source Sites (TSS), which collect human biospecimens and clinical data.
• Biospecimen 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.
• Genomic Characterization Center (GCC) that will genomically characterize NCI-provided CPTAC biospecimens to be characterized and analyzed by the PCCs.
• Clinical Data Resource (CDR) that will receive, qualify, store, and distribute clinical data.
• Quality Management System (QMS). The QMS works with all CPTAC awardees to define quality processes and metrics, and to track nonconforming events.
• Data 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.
• CPTAC Research 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 include:
• Data 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.
• Assay 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).
• Antibody 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.
• Proteomic 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.).
• Other NCI 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).

Applicants seeking a PCC award must be able to perform comprehensive characterizations of the proteomic composition of human biospecimens and samples from preclinical models. The nature, types, comprehensiveness, robustness, and quality of these characterizations must be appropriate to allow for a better understanding of the molecular complexity of specific cancer types. Moreover, PCCs will be expected to operate as an interactive group that will use various standardized proteomic analysis technologies.

In general, the activities of PCCs will comprise a Discovery Research Arm and Confirmatory Research Arm defined as follows.

• Discovery Research Arm refers to studies that include unbiased characterization of all detectable protein forms in a sample using analytically validated discovery proteomic technologies and platforms that meet the criteria described in Section IV.2. These types of characterizations should be conducted in a high-throughput manner and be deployable at the start of the project.
• Confirmatory Research Arm refers to accurate quantitative proteomic determinations of selected, cancer-relevant protein targets (identified through Discovery Research Arm) using analytically validated targeted proteomic technologies and platforms that meet the criteria described in Section IV.2. These types of measurements should be conducted in a high-throughput manner and be deployable at the start of the project.

Human Biospecimens. The emphasis of PCC research is on the clinical biospecimens. A goal for the entire PCC network is to characterize 5-6 human cancer types and analyze these cancers using a minimum of 1000 targeted assays for cancer-relevant proteins in clinical biospecimens. Human biospecimens that will be provided to PCCs will correspond to treatment-na ve tumors, accompanied by adjacent normal tissue when available. These specimens will be prospectively collected using standardized protocols optimized for proteomic analyses. 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 for each tumor type will be sufficient to ensure appropriate statistical power for the research findings. Biospecimens are to include well-annotated clinical data and undergo genomic characterization (such as whole exome sequencing, RNA sequencing, genotyping, and DNA copy number determinations). PCC applicants should anticipate receiving approximately 25 mg wet tissue weight per specimen.

Preclinical Samples. PCCs are expected to also analyze preclinical specimens (cell lines and xenografts) from two NCI programs: NCI’s Human Cancer Model Initiative (cell lines) and Patient-Derived Xenograft (PDX) Repository program. Collectively, PCCs are expected to conduct comprehensive protein characterization of 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.

The scientific scope of work proposed in the PCC application must cover all specific research objectives (described below). Applications with lesser scope will be viewed as non-responsive.

Primary Research Objective: Utilize one or more proteomic technologies to comprehensively characterize NCI-provided specimens (Discovery) and substantiate the selected targets in subsequent studies (Confirmatory).

General expectations for both Discovery and Confirmatory Research Arms for each PCC:

• Scientific capabilities, infrastructure, instrumentation, quality assurance processes, etc., to conduct all the required proteomic analyses as a part of PCC network-wide studies must be in place from the start of the project period. (This FOA will NOT support the development of such capabilities).
• Extensive expertise in the standardization of proposed proteomic platforms for both discovery and targeted proteomics approaches. Demonstration of rigor and reproducibility in all types of analyses.
• Ability to comprehensively characterize the protein composition in complex biological and clinical samples.
• Adequate capacity and throughput to fully characterize required specimens per year.
• Expertise in computational proteomic analysis methods.
• Develop and apply targeted multiplex proteomic assays to measure peptide/protein targets on required specimens per year.

Secondary Research Objective: Improve performance of the proteomic characterization technolog(ies)/platform(s) used in Primary Research Objective. Applicants must propose specific efforts to improve the selected technolog(ies)/platform(s) used in the PCC.

In addition, applicants must adhere to other general and specific considerations, including:

Coordination with PGDACs. Proteogenomic Data Analysis Centers (PGDACs; RFA-15-023) are expected to create multidisciplinary teams consisting of computational biologists, software engineers and experimental research scientists with diverse backgrounds whose aims will support innovative bioinformatics approaches 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 sequence, network and pathway level, including PTMs of proteins and protein-protein interaction. PGDACs are central to the CPTAC efforts. While bioinformatics teams in the PCCs may choose to conduct proteogenomic data analyses and contribute to the overall interpretation of the results, this activity (Level 2 and Level 3 analyses) is optional. It is required that the characterization data produced by the PCCs be shared with the PGDACs for more extensive and comprehensive integrative analyses to enhance deeper data visualization, analysis and interpretation. PCCs will provide all data and analysis results to the 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 as appropriate (see Section IV).

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.

PCCs 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 PCCs 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).

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
• 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 apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

An individual designated as PD/PI on a PGDAC application in response to RFA-15-023 cannot be designated as a PD/PI under this FOA. However, these individuals can serve as key persons within a PCC application.

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

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

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

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

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:

Henry Rodriguez, MS, PhD, MBA
Office of Cancer Clinical Proteomics Research
Center for Strategic Scientific Initiatives
Office of the Director
National Cancer Institute
31 Center Drive, Room 10A52, MSC 2580
Bethesda, MD 20892
Telephone: 301-451-8883
Fax: 301-496-7807
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.

Facilities and Other Resources: In addition to standard information, list/document unique and critical resources and/or infrastructure (e.g., any unique proteomic platforms/technologies/tools, access to instruments necessary to accomplish required throughput, capabilities of institutional information technology systems in terms of handling massive flows of data that are to be expected, etc.). For each main resource, provide key characteristics, such as throughput and/or ability to apply rigorous quality control/quality assurance procedures. If resources listed are shared (i.e., not exclusive to the proposed PCC, such as institutional information technology systems, shared resources cores, etc.), specify and document arrangements through which sufficient access will be granted for the purposes of the project. The list in this attachment may include the capacity for data submission and storage, as well as the ability to develop specific criteria for evaluating data quality. List briefly the formats of the datasets, and accompanying documentation and their volumes that are expected for the required and proposed PCC activities. Document the ability of the available resources to handle these needs as well as the ability to implement changes in the systems available if needed to integrate bioinformatics infrastructure across the PCCs (which may require such elements as: a uniform data reporting standard; optimization, integrated data mining, and others).

Furthermore, applicants should list any already established capabilities in enabling analytical validation for high-throughput proteomic platform(s) proposed in the application as defined under Research Objectives (Section I).

Other Attachments: Upload the items indicated as a single attachment using file name "SOPs" for instruments and data analyses QA/QC with appropriate performance metrics (this file name will become bookmark in the application). If SOPs to be used have been previously developed by the CPTAC, list those SOPs but do not attach their full text.

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

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

Total Costs for Assays. Applicants should budget for discovery and targeted proteomic assays to be developed and applied in biological and/or clinical samples in Discovery and/or Confirmatory Research Arms. Under Budget Justification, provide information on estimated cost of assays proposed on a per sample/per assay basis.

Funds for Pilot Studies. The budget requested must include $50,000 in direct costs per year to be allocated by each PCC specifically for pilot studies. The release of these restricted funds will be only for pilot studies approved by the CPTAC Steering Committee.

Note: Capital equipment requests (for equipment over $5,000) are not allowed under this FOA.

Site visits. Because of the complexity of the PCCs, NIH/NCI Program Staff members will conduct annual administrative site visits. PCC applicants should be prepared for annual visits and should budget appropriately (including travel for collaborators and other necessary costs).

Costs of participating in CPTAC meetings. Applicants should budget for the PDs/PIs and/or alternative designated representatives (in aggregate, up to 4 members of each PCC) to attend semi-annual face-to-face CPTAC investigator meetings.

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

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

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

Research Strategy: Instead of the standard sub-sections defined in Application Guide, Research Strategy must consist of the sub-sections A-D specified below .

Sub-Section A. Overview of the Proposed Proteome Characterization Center (PCC)

Present the overall vision for the proposed PCC including the following items:

• Outline the overarching aims for the PCC to address protein discovery, confirmation and prioritization, from a variety of cancer specimens and preclinical model samples.
• Describe the integration of the PCC Research Arms (Discovery and Confirmatory).
• Describe the rationale of how the proposed research approach will improve the understanding of cancer biology.
• Applicant Group.
• Provide details on collective aspects of the team expertise and capabilities (that are not covered and cannot be covered by individual biosketches). For example, outline the proposed Team structure and explain how group expertise of each member of the Team contributes to achieving the objectives of the proposed studies. Highlight how the diverse group expertise of the Team members synergizes in terms of the innovation of which the Team is capable, the flexibility they possess to redirect research when scientific progress warrants it, and their ability to anticipate new directions, based on their individual experience and ability to contribute to a collective effort. If applicable, provide evidence of previous successful collaborations among members of the applicant team.
• Without repeating information from individual biosketches, summarize the group’s collective proficiencies and capabilities in using the proposed proteomic technologies.
• Briefly describe the roles/contributions of research partners from other institutions (if applicable).
• Outline of strategies proposed to develop pilot studies that enhance a specific PCC’s efforts in advancing its overarching aims to identify and quantify proteins in specimens especially in small sample size. Pilot studies are to involve investigators inside or outside a specific PCC (no specific pilot studies are to be described in the application). See Subsection D below for additional instructions.

Preliminary data relevant to the proposed methods and/or specific technologies and platforms should be included in this sub-section. These data should demonstrate applicants' capability to meet the scientific requirements stated. Preliminary data included should also serve as evidence for the quality of the data that may be anticipated from the proposed technology platforms utilized by the applicants.

Sub-Section B. Discovery Research Arm. In this sub-section describe the following aspects.

a) Proteomic technology(ies)/platform(s). A platform/technology for the Discovery Research Arm is expected to have the following characteristics: a technology platform must be reproducible, quantitative and sensitive for comprehensive proteomic characterizations. For the purpose of this FOA, a discovery technology platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed and validated in at least one other laboratory; 2) is capable of generating reproducible results within and across laboratories using standards and metrics in high-throughput, large-scale proteomic research studies; and 3) has been previously published in a peer-reviewed journal.

Describe the plan for the proposed identification and quantification of proteins from the NCI-supplied samples in this FOA, including any analysis of PTMs and genetic aberrations. At a minimum, include experimental study design, throughput and enumeration of discovery capacity per year, efficiency, sensitivity, number of proteins and/or PTMs identified and quantified per characterization/analysis, error rate of identification, expertise (personnel) involved in the process, and how understanding the strengths/weaknesses of such measurements and the characteristics of the collected data can affect the interpretation of the results. The plan must address the amount of specimen materials needed to perform the proposed characterizations (wet tissue weight and cell culture).

b) Analytical capacity. Describe the current analytical capability and how the team plans to meet the requirements of:

• Characterizing and analyzing a minimum of 225 samples per year (of approximately 25 mg of wet tissue weight); and
• Identifying and quantifying at least 6000 unique proteins per tumor sample.

Identify your maximal analytical capability for the proposed technologies and realistic prospects for increasing respective throughput during Years 2 5. Provide timelines and milestones for these increases). Automated solutions for increased analysis throughput are highly encouraged. All equipment, instruments, procedures, etc. needed for the capabilities described must be operational, implemented, and available at the proposed start of the project period.

c) Quality Assurance/Quality Control criteria for proteomic technolog(ies)/platform(s). Describe a strategy to monitor and ensure the quality of instrument performance and data generated. PCCs should describe typical error rates for the proposed technology platforms to ensure data quality.

d). Data analysis. Three levels of data analysis are envisioned in the CPTAC program (see Section I). In the context of this FOA, PCCs are required to perform Level 1 data analysis, while Levels 2-3 are optional. Levels 2-3 data analyses are to be performed by and the PGDACs (RFA-CA-15-023) as requirements, in coordination with the PCCs, while the PTRCs (RFA-CA-15-022) are required to perform all three levels of data analysis. Applicants must describe how raw data will be analyzed for Level 1, including: descriptions of data processing, identification algorithms and quantitation strategies, databases used, and error rate analysis for protein/peptide identification and PTM site localization and quantitation), and how the raw data will be transferred to PGDACs for additional visualization, interpretation, and protein candidate prioritization for confirmatory studies. If mass spectrometry is to be used, clearly describe computational methodologies including algorithms, databases, and quality control procedures for protein identification, relative quantitation and PTMs site localization with a desirable protein-level identification error rate at <10-15%. An equivalent of metrics should be used for Level 1 analysis if other platforms are proposed. PCCs will submit their raw data, metadata and Level 1 data analysis results to the DCC.

Sub-Section C. Confirmatory Research Arm. In this sub-section describe the following aspects.

a) Proteomic technolog(ies)/platform(s). A platform/technology for Confirmatory Research Arm is expected to be reproducible, quantitative and multiplexed targeted methodology that has been analytically validated. A technology platform is considered analytically validated if it meets the following criteria: 1) has successfully been deployed in at least one other laboratory (preferably published in a peer-reviewed journal); 2) are high-throughput targeted assays capable of sampling the depth of proteomes studied that spans a wide dynamic range, specifically being able to measure protein/peptide concentrations in the range of low femtomole/microgram to low femtomole/milligram (proteins); 3) demonstrate the analytical rigor of quantitative data obtained from within and across laboratories using standards and metrics. For example, Multiple Reaction Monitoring Mass Spectrometry (MRM-MS), one of the quantitative technology platforms standardized by the CPTAC program, will be used as a reference point for criteria such as throughput, sensitivity, specificity, multiplexing capability, reproducibility, and portability (http://assays.cancer.gov). Other platforms/technologies are highly encouraged provided that they meet the specified analytical requirements. It is expected that a minimum of a Tier 2 analytical characterization for mass spectrometry (http://proteomics.cancer.gov/newsevents/newsannouncements/archive/2013/standardstargeted) or an equivalent of such criteria for other technologies/platforms (preferably with peer-reviewed publications or guidelines already in place).

b) Process for assay development. Describe the process for assay development to be used in confirmatory studies. Attributes to be included are throughput (assays development capacity and application per year to be a minimum of 120 samples is anticipated), quality control, reagents needed, timeline, and expertise (personnel) involved in the process.

c) Quality Assurance/Quality Control criteria for proteomic technolog(ies)/platform(s).

Describe a strategy to monitor and ensure the quality of instrument performance and data generated. Include plans to ensure implementation of metrics for instrument quality control and SOPs. Where applicable, use metrics and SOPs developed by CPTAC for instrument quality control during targeted assay deployment. For example, if targeted mass spectrometry assays are proposed, a PCC is also expected to apply a minimum of a Tier 2 analytical characterization (http://proteomics.cancer.gov/newsevents/newsannouncements/archive/2013/standardstargeted) or an equivalent of such criteria for other technologies and platforms preferably with citations of peer-reviewed publications or guidelines.

d. Data analysis. Describe how raw data from confirmatory studies will be analyzed (Level 1) and transferred to the PGDACs via the DCC for advanced analyses that may include additional visualization and/or interpretation.

Sub-Section D. Improvements of Proteomic Technologies. Describe the plans for technology development to improve the technolog(ies)/platform(s) used in the PCC. These efforts may serve the Discovery Research Arm, Confirmatory Research Arm, or both.

In the description, outline the plans for such aspects as:

• Enhancing sample throughput capabilities (expected in Years 2-5) beyond the initial level.
• Meaningful improvements of the selected characterization methods/technology platforms in terms of such aspects as: detection sensitivity, quantitation accuracy, resolution, and proteome coverage, and/or reducing unit costs per characterization/analysis. If applicable, include plans for any software development related to the generation and/or analysis of PCC data.
• Identifying sources of systematic error and bias and utilizing this information to improve results reliability.
• Developing strategies to take advantage of technology changes that may emerge during the project period, including a provision for a complete change in platform utilized, should it benefit the project.
• The plans must include the possibility that the PCC will participate in studies conducted across several PCCs on technology assessment.

Pilot studies for technology improvements. Under this heading (in sub-section D), list the areas/possible directions for which pilot studies are anticipated. Justify these choices by explaining why additional efforts in these areas/directions might be needed. Indicate how such projects will be formulated and conducted (if approved). Pilot studies could include, but are not limited to innovative approaches to Discovery and/or Confirmatory Research Arms studies. Note that concepts for such studies to be formulated by the awardee will be expected to reflect the individual needs of that awardee. Nonetheless, these individual concepts will be evaluated and coordinated by the CPTAC Steering Committee to optimize the efforts at the Network level. As pilot studies proposed by each Center (post-award) will require beyond normal stewardship (i.e., Project Scientists responsible for the U24 awards in coordination with the CPTAC Steering Committee, see Cooperative Agreement Terms and Conditions of the Award, under "Areas of Joint Responsibilities" in Section VI.2), a description of the process to obtain the approval of such studies, which may be collaborative, should be included for peer review in order to determine fairness at the time of application. Subsequently, the CPTAC Steering Committee and the involved Project Scientists should advise which studies would be supported to enhance and accelerate the overall goals of the program.

(No pilot studies are to be proposed in the applications submitted in response to this FOA).

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 modifications:

• All applications, regardless of the amount of direct costs requested for any one year, should address a Data Sharing Plan.
• Data Sharing Plan should be consistent with accomplishing the goals of the CPTAC program. Specifically:
• Data Sharing Plan should acknowledge that all PCC awardees will be required to upload all of their data to the CPTAC DCC during the five-year funding period.
• The plan should specify how and when data obtained throughout the Discovery and Confirmatory Research Arms and algorithms produced will be released and shared. The sharing timing and frequency are expected to be consistent with achieving the goals of CPTAC (such as submitting all data to the CPTAC DCC within 30-60 days after completion of data generation and Level 1 data analysis, to become publicly available after appropriate Quality Assurance as determined by the CPTAC Steering Committee), and with NIH data sharing guidelines.
• The plan should also adhere to the general proteomic data sharing principles established such as in the Amsterdam Principles for mass spectrometry (http://proteomics.cancer.gov/resources/opendatapolicy) or an equivalent for other technologies/platforms.
• The plan should assume that, similar to TCGA and other programs, CPTAC data will be subject to a period of embargo (https://cptac-data-portal.georgetown.edu/cptac/aboutData/disclaimer).
• Other Resources Sharing: Consistent with achieving the goals of this program, all resources generated by the PCCs (e.g., standards, reagents, and SOPs) will promptly become available through a CPTAC Public Resource (CPTAC Data Portal, Assay Portal and Antibody Portal; http://protoemics.cancer.gov). It is anticipated that other distribution avenues will be made available by the NCI if determined to be necessary. Resource sharing plans would be expected to describe the type(s) of resources that will become available through the proposed center.
  Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.
• CPTAC Intellectual Property Policy: Consistent with achieving the goals of this program and maximizing the benefit of all research funded as part of the CPTAC program for the improvement of public health through discoveries of the scientific community, CPTAC Data Sharing and Data Release policies expect a broad freedom-to-operate for all users of CPTAC data (e.g., by rapidly placing all data in the public domain). In addition, computer algorithms produced specifically to analyze CPTAC data, software source code or other resources (reagents) made possible under the auspices of CPTAC are expected to be made broadly available. It is expected that any data producer in the PCCs will make all information available, without requirement for licensing, for applications such as, but not necessarily limited to, the use of markers in developing assays or targets for therapeutic and diagnostic purposes. All PCC members and affiliated institutions must acknowledge agreement to the CPTAC Intellectual Property Policy. Investigators and their institutions must expressly acknowledge and agree to abide by this policy.
• 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.

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 and responsiveness by NCI, 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.

For this particular announcement, note the following:

In determining the merit of applications, reviewers will assess the applicants' capabilities and plans in terms of the stated scientific, technological, and organizational requirements.

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 PCC 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 PCC that by its nature is not innovative may be essential to advance a field.

Does the PCC address an important problem or a critical barrier to progress in the field? If the aims of the PCC 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: Will the proposed PCC significantly advance the knowledge of cancer cell complexities at the proteogenomic level? How strong is the rationale that the PCC, as proposed, will contribute meaningfully to improved understanding of fundamental issues relevant to cancer biology?

Are the PD(s)/PI(s), collaborators, and other researchers well suited to the PCC? 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 PCC 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 PCC?

Specific to this FOA: How sufficient is the breadth of team expertise in terms of the collective potential for creative and innovative approaches, the ability to anticipate new directions and flexible reprogramming of efforts, if needed, etc.? If the team members collaborated previously, how valuable are those past collaborative experiences to the proposed PCC??

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?

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

Specific to this FOA: How appropriate are the overall strategies for the Discovery and Confirmation Research Arms (including comprehensive characterization, targeted assay development, data analyses, quality assurance/quality control, etc.)? How convincing is the evidence provided to document that the applicant team can (1) reach the specified initial minimum rate of sample characterizations and increase this rate during the project period as required; (2) efficiently utilize the amounts of specimen materials (wet tissue weight and cell culture) provided by the NCI for the types of proteomic characterizations proposed; and (3) perform data analysis while being able to control error rate for protein discovery using computational tools? How sufficient and realistic are the plans for technological improvements and pilot studies? What is the likelihood that the PCC, as proposed, will operate with sufficiently high scientific rigor?

If the PCC 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: Are the proposed Center organization and general strategies appropriate to facilitate required interactions and/or collaborations with other PCCs, PGDACs, and additional parts of the CPTAC research resources?

As applicable for the PCC 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.

Not Applicable

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

Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic Data Sharing Plan.

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

Applications will be evaluated for scientific and technical merit by (an) appropriate Scientific Review Group(s) convened by the NCI, 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 National Cancer Advisory Board. The following will be considered in making funding decisions:

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

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:

• Overseeing, directing, and coordinating scientific and administrative activities of the PCC;
• Defining research goals, determining and/or approving experimental approaches, and setting project milestones and timelines;
• Overseeing the conduct of research at the PCC, including such aspects as: experimental activities, data collection, quality control, interim data and safety monitoring, final data analysis and interpretation, and preparation of results for publications;
• Ensuring the timely sharing of PCC-generated data across the PCC and the entire CPTAC program through CPTAC DCC as appropriate;
• Participating in the activities of the CPTAC Steering Committee as voting members;
• Accepting and implementing all scientific and policy recommendations approved by the CPTAC Steering Committee to the extent consistent with applicable grant regulations;
• Committing an effort to the PCC of at least 2.4 person-months by each PD/PI;
• Preparing for annual administrative site visits by NCI Program Staff;
• Providing other information as might be requested by Project Scientist (e.g., on annual Center milestones, goals for throughput, procedures, etc.)
• Monitoring the completion of established goals and benchmarks within the timeframe and budget proposed;
• Submitting a list of prioritized discovered high priority protein targets for consideration by the Protein Candidate Selection Subcommittee for subsequent confirmatory studies;
• Coordinating and encouraging inter-network collaborations;
• Participating in the semi-annual PD/PI meeting organized by NCI;
• Ensuring that proper process management methods are executed for planning, monitoring, and managing the workload over the award period, and are expected to provide update reports to NCI Program Staff upon request.

Awardees will be expected to participate in an external evaluation process of the CPTAC program coordinated by NCI Program Staff.

Investigators from each PCC award will be expected to participate in various task-oriented working groups together with members from other CPTAC sub-programs that might be formed, as needed, e.g., as subcommittees of the CPTAC Steering Committee.

The primary PCC awardee institution and all other institutions participating in a given PCC must agree to share and release results, data, research materials, and any other resources necessary and relevant to the PCC s award. Awardees will retain custody of and have primary rights to the data and the 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:

Designated NCI Program Staff members will have substantial programmatic involvement as Project Scientists. Specifically, the NCI Project Scientists will:

• Serve as voting members of the CPTAC Steering Committee and its subcommittees as appropriate;
• In collaboration with the PDs/PIs and the CPTAC Steering Committee, ensure the CPTAC network functions as a unified whole to achieve the goals of the program;
• Coordinate collaborative research efforts that involve multiple PCCs, PGDACs and PTRCs when necessary;
• Monitor the operations of the CPTAC program and make recommendations on overall project directions and allocations of project funds;
• Assist in avoiding unwarranted duplications of effort across the CPTAC awardees;
• Review the progress of individual CPTAC awardees and specific activities shared among the awardees;
• Assist the awardees as a resource in stimulating their broader interaction with other NCI and NIH programs to disseminate results and outcomes from the CPTAC program and effectively leverage existing NIH/NCI resources and infrastructures;
• Coordinate the supply of specimens and reagents for analyses by the CPTAC program through the CPTAC Research Resources whenever applicable;
• Co-organize and participate in the semi-annual meeting of CPTAC investigators;
• Ensure the availability of data and related resources developed during the course of the CPTAC program to the scientific community at large;
• Participate in data analyses, interpretations, and co-authorship of CPTAC publications as appropriate and jointly agreed through the CPTAC Steering Committee.
• Ensuring that decisions, recommendations, and policies of the CPTAC Steering Committee are consistent with applicable grant regulations.

Areas of Joint Responsibility include:

CPTAC Steering Committee. CPTAC Steering Committee will serve as the primary governing body of the CPTAC program. The Committee will be jointly established by all the awarded PDs/PIs of the PCCs, the PGDACs, the PTRCs and the NCI Program Staff members. The CPTAC Steering Committee will provide strategic coordination for the activities of the PCC network and the CPTAC program overall.

Voting members of the CPTAC Steering Committee will include:

• One representative from each PCC;
• One representative from each PGDAC;
• One representative from each PTRC; and
• One representative from the NCI Office of Cancer Clinical Proteomics Research.

The CPTAC Steering Committee will elect three representatives (one each from the PCC sub-program, PGDAC sub-program, and PTRC sub-program) as its co-chairs (or alternating chairs) for a pre-determined length of time).

Non-Voting Members:

• Additional representatives from other NCI-supported research resources serving CPTAC may also participate as non-voting members and as determined by the CPTAC Steering Committee.
• The CPTAC Steering Committee may decide to add other non-voting members as needed, e.g., to provide specific scientific expertise and/or to include patient advocates.

CPTAC Steering Committee:

• CPTAC Steering Committee will establish a Protein Selection Subcommittee (see below).
• CPTAC Steering Committee may also establish other subcommittees as it deems appropriate.

It is anticipated that the CPTAC Steering Committee will formulate strategic decisions and policies for consortium-wide activities. The CPTAC awardees will be required to accept and implement these decisions and policies to the extent consistent with applicable grant regulations.

The activities of the CPTAC Steering Committee are expected to include the following:

• Establishing operational guidelines and policies to meet the goals of the CPTAC network and monitor the implementation of these guidelines and policies;
• Reviewing progress of the CPTAC sub-programs on a regular basis;
• Developing quality assurance goals for all network functions, specimens, technology and data for the CPTAC network;
• Following-up on action items from the CPTAC Steering Committee in a timely fashion;
• Approving recommendations and development plans from the Protein Candidate Selection Subcommittee (see below);
• Prioritizing and recommending pilot studies for execution;
• Organizing semi-annual meetings of CPTAC investigators.
• Coordinating the development of a standard data reporting system by the CPTAC Steering Committee (e.g., updating the reporting system currently used in CPTAC);
• Developing operating guidelines, quality control procedures, and consistent policies for the CPTAC network.

Protein Candidate Selection Subcommittee. The members of the Protein Candidate Selection Subcommittee will include a set number of members of the CPTAC Steering Committee (or their nominees); NIH/NCI Program Staff members; and additional scientific experts as deemed necessary by the committee.

The activities of the Protein Candidate Selection Subcommittee will include the following:

• Consolidating the lists of prioritized proteins from each CPTAC sub-program’s inventory and prioritization process, including reviewing scientific justifications for developing multiple targeted proteomic assays against the same protein originating from a given "parent gene," such as its protein variants, modified forms, etc.
• Recommending a biological- and clinical-based selection of protein candidates for clinical research studies;
• Recommending reagents and specimens to be used for the selected protein candidates.

Recommendations by the Protein Candidate Selection Subcommittee will be reviewed and approved by the CPTAC Steering Committee.

CPTAC External Scientific Panel. The CPTAC Steering Committee will establish a panel of external experts (i.e., individuals with appropriate expertise who are NOT affiliated with any of the CPTAC awardees). The primary role of the External Scientific Panel will be to provide independent assessment of research directions and progress of the CPTAC awardees. The External Scientific Panel will annually evaluate research conducted by the CPTAC members, including the review of the overall program metrics, progress of individual awardees, strategic plans, etc. The panel may also recommend to the Steering Committee new research opportunities to explore, adjustments in priorities, and/or approaches as well as other steps/actions to advance the overall CPTAC goals.

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. In addition to the annual RPPR, a detailed interim Center progress report will be required once a year. This report should be submitted directly to the NCI Project Scientist. The interim report will be required to be formatted following standardized guidelines developed by the NCI Program Staff and may be changed according to programmatic needs based on discussions among the CPTAC Steering Committee members.

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

For general aspects of the entire Clinical Proteomic Tumor Analysis Consortium, contact:

Henry Rodriguez, MS, PhD, MBA
National Cancer Institute (NCI)
Telephone: 301-451-8883
Email: [email protected]

For issues pertaining specifically to Proteome Characterization Centers, contact:

Emily Boja, PhD
National Cancer Institute (NCI)
Telephone: 301-451-8883
Email: [email protected]

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

Mutema Nyankale
National Cancer Institute (NCI)
Telephone: 240-276-5987
Email: [email protected]

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