Department of Health
and Human Services (HHS)
and Human Services (HHS)
EXPIRED
National Institutes of Health (NIH)
National Cancer Institute (NCI)
U24 Resource-Related Research Projects Cooperative Agreements
This Funding Opportunity Announcement (FOA) supports the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) managed by the Office of Cancer Clinical Proteomics Research (OCCPR). CPTAC leverages recent advancements in cancer proteomics and genomics to better understand the complexity between the proteome and the genome in cancer and accelerate research in these areas by disseminating resources for the scientific community. The program will continue to 1) support an increased understanding of cancer through comprehensive proteogenomic approaches, 2) expand support for the development of novel cancer diagnostics and therapeutics by implementing proteogenomic strategies to understand drug response and development of resistance in the context of a clinical trial, and 3) accelerate its translation through public resources (such as data, assays, images and reagents) that catalyze hypothesis-driven science.
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 and preclinical models) will be provided by the NCI.
PCCs will interact with additional CPTAC Centers that include:
30 days prior to application due date..
| Application Due Dates | Review and Award Cycles | ||||
|---|---|---|---|---|---|
| New | Renewal / Resubmission / Revision (as allowed) | AIDS | Scientific Merit Review | Advisory Council Review | Earliest Start Date |
| June 30, 2021 | Not Applicable | Not Applicable | November 2021 | January 2022 | April 2022 |
All applications are due by 5:00 PM local time of applicant organization. All types of non-AIDS applications allowed for this funding opportunity announcement are due on the listed date(s).
Applicants are encouraged to apply early to allow adequate time to make any corrections to errors found in the application during the submission process by the due date.
No late applications will be accepted for this Funding Opportunity Announcement.
Not Applicable
It is critical that applicants follow the instructions in the Research (R) Instructions in the SF424 (R&R) Application Guide,except where instructed to do otherwise (in this FOA or in a Notice from 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.
Purpose
This Funding Opportunity Announcement (FOA) supports the NCI Clinical Proteomic Tumor Analysis Consortium (CPTAC) managed by the Office of Cancer Clinical Proteomics Research (OCCPR). This reissuance of the CPTAC program seeks to expand the current achievements in clinical cancer proteogenomic discoveries and infrastructure to accelerate molecularly oriented cancer research toward basic discovery and clinical impact. 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 questions, such as the ability to predict which treatment options are most effective for a patient's tumor.
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 samples that will be genomically-characterized. These samples will be provided by the NCI.
PCCs will interact with additional CPTAC Centers that include:
This FOA is open to all qualified applicants regardless of whether 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 and antibodies) are to be made publicly available to the research community through CPTAC's Data Warehouse -- Proteomics data in CPTAC’s Data Coordinating Center (DCC) and NCI’s Proteomic Data Commons (PDC), assays in CPTAC’s Assay Portal, antibodies in CPTAC’s Antibody Portal, and coordinated with the Center for Cancer Genomics and the Cancer Imaging Program, genomics data in the Genomic Data Commons (GDC) and medical images in The Cancer Imaging Archive (TCIA) and NCI’s Imaging Data Commons (IDC), and other pertinent 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.
Background
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 discovery and translational research, and clinical impact.
The CPTAC program (RFA-CA-07-012) was launched in 2006 as a part of the Clinical Proteomic Technologies for Cancer initiative at the NCI. The purpose of CPTAC was to develop standardized proteomic workflows to ensure analytical rigor and reproducibility of proteomic measurements. Highlights include the standardization of mass spectrometry (MS) methodologies for comprehensive proteomics (discovery proteomics), standardization of MS methodologies for targeted proteomics (such as multiple reaction monitoring [MRM]), adoption of a MRM assay for thyroglobulin by clinical reference laboratories, development of an open-source computational tool (Skyline) for designing assays (such as MRM) that is supported by major MS instrument vendors, the development of mock 510(k) device clearance documents for regulatory approval of fit-for-purpose targeted proteomic assays in collaboration with the Food and Drug Administration (FDA) and the American Association for Clinical Chemistry (AACC), and the development of open data sharing policies in proteomics that are supported by peer-reviewed journals.
The second iteration of CPTAC began in 2011 (RFA-CA-10-016) and applied these new standardized and harmonized proteomic workflows to genomically characterized tumors (such as those from The Cancer Genome Atlas (TCGA) and others). The goals were to comprehensively characterize the relationships between proteins derived from altered genes and related biological processes to determine if the additional layer of protein biology would further enhance the molecular understanding of cancer in ways not possible through genomics alone. The major insights gained from these studies were that genomic changes often do not result in predictable effects at the protein level, and that post-translational modifications (PTMs) such as protein phosphorylation provide critical data on functional regulations that genomics alone does not resolve. Thus, integrating comprehensive proteomic characterization with comprehensive genomic characterization can provide more information and insight into cancer development and growth. All data and analytical tools were made broadly available to the research community through public databases (CPTAC's Research Resources: Data Portal, https://proteomics.cancer.gov/data-portal; Assay Portal, https://assays.cancer.gov; Antibody Portal, https://antibodies.cancer.gov), in order to democratize proteomics science.
With the success of the prior issuance on proteomic measurements adding an additional dimension to tumor biology, in 2016 NCI expanded CPTAC’s infrastructure to include prospective tissue collection, genomic and proteomic characterization and analysis (global and phospho proteomics), and resource dissemination. The overarching goals of the third iteration were (i) to increase our understanding of cancer by comprehensively characterizing tumors (proteomically and genomically), (ii) to continue to produce public resources (data, assays, images, reagents) that catalyze hypothesis-driven science, and (iii) to support clinical research projects [using both sets of omics] that address mechanisms of treatment response, resistance, or toxicity. To achieve these goals, CPTAC evolved into two united and coordinated sub-programs: The Tumor Characterization Program and the Translational Research Program, whose activities are performed by Proteome Characterization Centers (PCCs, supported by RFA-CA-15-021), Proteogenomic Data Analysis Centers (PGDACs, supported by RFA-CA-15-023) and Proteogenomic Translational Research Centers (PTRCs, supported by RFA-CA-15-022). Such an approach to precision oncology has been highly successful in proving the scientific benefits of integrating proteomic analysis with genomics to produce a more unified understanding of cancer, while creating open community resources across several collaborating entities that are widely used by the global cancer community.
Overall CPTAC Structure and Functions
CPTAC has two united and coordinated sub-programs, whose activities are carried out through three types of cooperative centers. The united and coordinated sub-programs are:
The cooperative centers are:
Additional resources supported by the NCI:
Research Objectives and Main Requirements for this FOA
Applicants seeking a PCC award must be able to perform comprehensive characterizations of the proteomic composition of human biospecimens and samples from preclinical models, including fresh frozen, formalin fixed paraffin-embedded and optimal cutting temperature (OCT)-embedded. 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 leverage and use various standardized proteomic analysis technologies within the Center.
In general, the activities of PCCs comprise a Discovery Research Arm, which refers to studies that include unbiased characterization of all detectable protein forms in a sample (discovery proteomics), followed by accurate quantitative proteomic determinations of selected, cancer-relevant protein targets (targeted proteomics), typically identified through the previously conducted unbiased protein measurements (or curation of scientific literature). All proteomic measurement technologies and platforms need to be analytically validated in a manner that meets 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.
Human Biospecimens. The emphasis of PCC research is to analyze clinical human biospecimens. A goal for the entire PCC network is to comprehensively characterize 5-6 human cancer types. Human biospecimens that will be provided to PCCs will correspond to treatment-na ve tumors, accompanied by normal adjacent tissue when available. These specimens will be prospectively collected using established standardized protocols optimized for proteomic analyses. It is anticipated that there will be 150 cases/specimens (tumor with adjacent normal) for each cancer type. The number of specimens for each tumor type will be sufficient to ensure appropriate statistical power. 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). In addition, metastatic and recurring cancers as well as retrospective samples with patient outcome data will also be explored. PCC applicants should anticipate receiving approximately 25 mg wet tissue weight per specimen.
Preclinical Samples. PCCs are expected to also analyze preclinical samples (such as xenografts and organoids) from NCI’s Patient-Derived models program. Collectively, PCCs are expected to conduct comprehensive protein characterization of preclinical samples (anticipated up to 2000 samples).
To be responsive, the scientific scope of work proposed must cover all Specific Research Objectives (described below).
Primary Research Objective: Utilize one or more proteomic technologies to comprehensively characterize NCI-provided specimens.
General expectations for the Discovery Research Arm for each PCC:
Secondary Research Objective: Improve performance of the proteomic characterization technology(ies)/platform(s) used in Primary Research Objective. Applicants must propose specific efforts to improve the selected technology(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-CA-21-024) 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) integrate, visualize and analyze the data at sequence, network and pathway level, which includes not only genomic and global proteomics but also PTMs of proteins and protein-protein interactions. 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, these activities (Level 2 and Level 3 analyses) are 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 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).
Governance of the NCI Clinical Proteomic Tumor Analysis Consortium
The CPTAC program will be governed by a 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 the SC are provided in Section VI. Award Administration Information, Terms and Conditions of Cooperative Agreement, Areas of Joint Responsibility.
Evaluation of the Program
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 Evaluation Panel (ESEP) (as described in Section VI).
See Section VIII. Other Information for award authorities and regulations.
See Section VIII. Other Information for award authorities and regulations.
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. See Section VI.2 for additional information about the substantial involvement for this FOA.
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types. Only those application types listed here are allowed for this FOA.
Not Allowed: Only accepting applications that do not propose clinical trials.
Need help determining whether you are doing a clinical trial?
NCI intends to commit $3,400,000 in FY 2022 to fund up to 3 awards.
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 $750,000 in direct costs per year and need to reflect the actual needs of the proposed project.
Applicants may request up to 5 years of support.
NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made from this FOA.
Higher Education Institutions
The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:
Nonprofits Other Than Institutions of Higher Education
For-Profit Organizations
Local Governments
Federal Governments
Other
Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations
Applicant organizations must complete and maintain the following registrations as described in the SF 424 (R&R) Application Guide to be eligible to apply for or receive an award. All registrations must be completed prior to the application being submitted. Registration can take 6 weeks or more, so applicants should begin the registration process as soon as possible. The NIH Policy on Late Submission of Grant Applications states that failure to complete registrations in advance of a due date is not a valid reason for a late submission.
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 companion RFA-CA-21-024 (U24) cannot be designated as a PD/PI under this FOA. However, these individuals can serve as key personnel 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:
The application forms package specific to this opportunity must be accessed through ASSIST, Grants.gov Workspace or an institutional system-to-system solution. Links to apply using ASSIST or Grants.gov Workspace are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.
Letter of Intent
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:
The letter of intent should be sent to:
Henry Rodriguez, M.S., Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-781-3370
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 that is available (PCC exclusive 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 instruments, institutional information technology systems, shared resources cores, etc.), specify and document arrangements through which priority and 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 and volumes of the datasets and accompanying documentation 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 as 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 established capabilities that enable 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 a 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.
R&R Budget
All instructions in the SF424 (R&R) Application Guide must be followed.
Total Costs for Sample Characterization. Applicants should budget for comprehensive and targeted proteomic data generation, with Level 1 data analysis in the Discovery Research Arm. Under Budget Justification, provide information on estimated cost proposed on a per sample basis.
Restricted Funds for Pilot Studies. The budget requested must include $30,000 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 related 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 the 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:
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 as they relate to comprehensive and targeted proteomic data generation.
Comprehensive (untargeted and unbiased) Proteomic Data Generation:
a) Proteomic technology(ies)/platform(s). A technology/platform 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 comprehensive (untargeted and unbiased) 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 (such as fresh frozen, OCT, FFPE human tumors, animal cancer models) in this FOA, including any analysis of PTMs and other -omics data (such as metabolomics). 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 for solid tumors, and/or number of cells for samples such as organoids).
b) Analytical capacity. Describe the current analytical capability and how the team plans to meet the requirements of:
Identify your maximal reproducible analytical capability for the proposed technologies and realistic prospects for increasing respective sample throughput and/or reducing sample quantity input requirement to quantify proteins from clinical specimens during Years 2 5. Provide timelines and milestones for these improvements. Automated solutions for increased analysis throughput are highly encouraged.
c) Quality Assurance/Quality Control criteria for proteomic technology(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 the PGDACs (RFA-CA-21-024) as requirements, in coordination with the PCCs. 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 software tools to be used for identification and quantitation, database, and data analysis parameter (including, but not limited to, mass tolerance, number of mis cleavage, fixed and variable modification, false discovery rate (FDR), and number of peptides per protein). 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 and to PGDACs.
Targeted Proteomic Data Generation:
a) Proteomic technology(ies)/platform(s). A technology/platform is expected to be a 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) involves high-throughput targeted assays capable of sampling the depth of proteomes studied and spanning 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 (https://assays.cancer.gov). Other technologies/platforms are highly encouraged provided that they meet the specified analytical requirements. A minimum of a Tier 2 analytical characterization for mass spectrometry (https://proteomics.cancer.gov/assay-portal/about/assay-characterization-guidance-documents) or an equivalent of such criteria for other technologies/platforms (preferably with peer-reviewed publications or guidelines already in place) is expected.
b) Process for assay development. Describe the process for targeted assay development. Attributes to be included are target selection, throughput, assay development capacity, quality control, reagents needed, timeline, measurement instrumentation, configuring assay panels and evaluating performance, and expertise (personnel) involved in the process. Throughput capacity for the developed and deployed assays is expected, with a minimum of 150 samples per year.
c) Quality Assurance/Quality Control criteria for proteomic technology(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 for sample storage/processing/analyses. Where applicable, use metrics and SOPs previously developed by CPTAC. For example, if targeted mass spectrometry assays are proposed, a PCC is also expected to apply a minimum of a Tier 2 analytical characterization (https://proteomics.cancer.gov/assay-portal/about/assay-characterization-guidance-documents) 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 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 C. Improvements of Proteomic Technologies
Describe the plans for technology development to improve the technology(ies)/platform(s) used in the PCC. These efforts may serve as the Discovery Research Arm.
In the description, outline the plans for such aspects as:
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.
The following modifications also apply:
The following modifications also apply:
Note that the NCI Program Staff may negotiate modifications to these plans prior to funding.
When involving human subjects research, clinical research, and/or NIH-defined clinical trials (and when applicable, clinical trials research experience) follow all instructions for the PHS Human Subjects and Clinical Trials Information form in the SF424 (R&R) Application Guide, with the following additional instructions:
If you answered Yes to the question Are Human Subjects Involved? on the R&R Other Project Information form, you must include at least one human subjects study record using the Study Record: PHS Human Subjects and Clinical Trials Information form or Delayed Onset Study record.
Study Record: PHS Human Subjects and Clinical Trials Information
All instructions in the SF424 (R&R) Application Guide must be followed.
Note: Delayed onset does NOT apply to a study that can be described but will not start immediately (i.e., delayed start).All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov
Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit How to Apply Application Guide. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Dealing with System Issues guidance. For assistance with application submission, contact the Application Submission Contacts in Section VII.
Important reminders:
All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.
The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.
See more tips for avoiding common errors.
Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.
Applicants are required to follow the instructions for post-submission materials, as described in the policy. Any instructions provided here are in addition to the instructions in the policy.
Only the review criteria described below will be considered in the review process. Applications submitted to the NIH in support of the NIH mission 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 project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? Is the prior research that serves as the key support for the proposed project rigorous? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field?
Specific to this FOA: How well 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 project? If Early Stage Investigators or those in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project?
Specific to this FOA: How 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 project? Have the investigators included plans to address weaknesses in the rigor of prior research that serves as the key support for the proposed project? Have the investigators presented strategies to ensure a robust and unbiased approach, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? Have the investigators presented adequate plans to address relevant biological variables, such as sex, for studies in vertebrate animals or human subjects?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of individuals of all ages (including children and older adults), justified in terms of the scientific goals and research strategy proposed?
Specific to this FOA: How appropriate is the overall strategy for the Discovery Research Arm (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 and/or reduce sample quantity input requirement to quantify proteins from clinical specimens during the project period as required; (2) efficiently utilize the amounts of specimen materials (wet tissue weight and/or number of cells [e.g., for organoids]) 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? What is the likelihood that the PCC, as proposed, will operate with sufficiently high scientific rigor?
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: How appropriate are the proposed Center’s organization and general strategies to facilitate required interactions and/or collaborations with other PCCs, PGDACs, and additional parts of the CPTAC research resources?
As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.
Protections for Human Subjects
For research that involves human subjects but does not involve one of the 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 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.
Inclusion of Women, Minorities, and Individuals Across the Lifespan
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 individuals of all ages (including children and older adults) 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.
Vertebrate Animals
The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.
Biohazards
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.
Resubmissions
Not Applicable
Renewals
Not Applicable
Revisions
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.
Applications from Foreign Organizations
Not Applicable.
Select Agent Research
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).
Resource Sharing Plans
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: (1) Data Sharing Plan; (2) Sharing Model Organisms; and (3) Genomic Data Sharing Plan (GDS).
Authentication of Key Biological and/or Chemical Resources:
For projects involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.
Budget and Period of Support
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 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 will receive a written critique.
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.
Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by the National Cancer Advisory Board. The following will be considered in making funding decisions:
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 recipient'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.
Institutional Review Board or Independent Ethics Committee Approval: Recipient institutions must ensure that protocols are reviewed by their IRB or IEC. To help ensure the safety of participants enrolled in NIH-funded studies, the awardee must provide NIH copies of documents related to all major changes in the status of ongoing protocols.
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, Recipients, and Activities. More information is provided at Award Conditions and Information for NIH Grants.
Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights laws that prohibit discrimination on the basis of race, color, national origin, disability, age and, in some circumstances, religion, conscience, and sex. This includes ensuring programs are accessible to persons with limited English proficiency. The HHS Office for Civil Rights provides guidance on complying with civil rights laws enforced by HHS. Please see https://www.hhs.gov/civil-rights/for-providers/provider-obligations/index.html and http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html.
HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research. For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA.
Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at https://www.hhs.gov/ocr/about-us/contact-us/index.html or call 1-800-368-1019 or TDD 1-800-537-7697.
In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.
The following special terms of award are in addition to, and not in lieu of, otherwise applicable U.S. Office of Management and Budget (OMB) administrative guidelines, U.S. Department of Health and Human Services (DHHS) grant administration regulations at 45 CFR Part 75, 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 recipients 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 recipients for the project as a whole, although specific tasks and activities may be shared among the recipients and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
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:
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.
Details on the composition, functions, and responsibilities of CPTAC Steering Committee are following.
Voting members of the CPTAC Steering Committee will include:
Non-Voting Members:
It is anticipated that the CPTAC Steering Committee will formulate strategic decisions and policies for consortium-wide activities. The CPTAC award recipients 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:
CPTAC External Scientific Evaluation Panel. The CPTAC Steering Committee will help establish a panel of external experts (i.e., individuals with appropriate expertise who are NOT affiliated with any of the CPTAC award recipients). The primary role of the External Scientific Evaluation Panel will be to provide independent assessment of research directions and progress of the CPTAC award recipients. The External Scientific Evaluation Panel will annually evaluate research conducted by the CPTAC members, including the review of the overall program metrics, progress of individual recipients, 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:
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 recipient. This special dispute resolution procedure does not alter the recipient's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
A final RPPR, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Service Desk (Questions regarding ASSIST, eRA Commons, application errors and warnings, documenting system problems that threaten submission by the due date, and 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)
General Grants Information (Questions regarding application instructions, application processes, and NIH grant resources)
Email: [email protected] (preferred method of contact)
Telephone: 301-945-7573
Grants.gov Customer Support (Questions regarding Grants.gov registration and Workspace)
Contact Center Telephone: 800-518-4726
Email: [email protected]
For general aspects of the entire Clinical Proteomic Tumor Analysis Consortium, contact:
Henry Rodriguez, M.S., Ph.D., M.B.A.
National Cancer Institute (NCI)
Telephone: 240-781-3370
Email: [email protected]
For issues pertaining specifically to Proteome Characterization Centers, contact:
Tara Hiltke, Ph.D.
National Cancer Institute (NCI)
Telephone: 240-781-3435
Email: [email protected]
Referral Officer
National Cancer Institute (NCI)
Telephone: 240-276-6390
Email: [email protected]
Shane Woodward
National Cancer Institute (NCI)
Telephone: 240-276-6303
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.