National Institutes of Health (NIH)
This Funding Opportunity Announcement (FOA) is developed as a Common Fund initiative (http://commonfund.nih.gov/) through the NIH Office of the NIH Director, Office of Strategic Coordination (http://dpcpsi.nih.gov/osc/). This FOA will be administered by the National Human Genome Research Institute (NHGRI) (http://www.nhgri.nih.gov/) on behalf of the NIH (http://www.nih.gov/). Other participating Institutes include:
National Cancer Institute (NCI)
National Eye Institute (NEI)
National Heart, Lung, and Blood Institute (NHLBI)
National Human Genome Research Institute (NHGRI)
National Institute on Aging (NIA)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
National Institute of Allergy and Infectious Diseases (NIAID)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
National Institute on Deafness and Other Communication Disorders (NIDCD)
National Institute of Dental and Craniofacial Research (NIDCR)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
National Institute on Drug Abuse (NIDA)
National Institute of Environmental Health Sciences (NIEHS)
National Institute of General Medical Sciences (NIGMS)
National Institute of Neurological Disorders and Stroke (NINDS)
Division of Program Coordination, Planning and Strategic Initiatives, Office of Research Infrastructure Programs (ORIP)
Office of Research on Women’s Health (ORWH)
Limited Competition: Knockout Mouse Phenotyping Project Database (UM1)
UM1 Research Project with Complex Structure Cooperative Agreement
Reissue of RFA-RM-10-012
RFA-RM-15-017, UM1 Research Project with Complex Structure Cooperative Agreement
93.310, 93.866; 93.847; 93.856; 93.855; 93.859; 93.172; 93.273; 93.233; 93.839; 93.838; 93.837; 93.867; 93.113; 93.865; 93.396; 93.279; 93.313; 93.173; 93.846; 93.853; 93.121; 93.351
This initiative is funded through the NIH Common Fund, which supports cross-cutting programs that are expected to have exceptionally high impact. All Common Fund initiatives invite investigators to develop bold, innovative, and often risky approaches to address problems that may seem intractable or to seize new opportunities that offer the potential for rapid progress. The purpose of the Knockout Mouse Phenotyping Project (KOMP2) is to produce a comprehensive resource of null-mutant mice, and associated phenotype data, for the purpose of elucidating functional information for each protein-coding gene in the mammalian genome. The goal of this FOA is to provide informatics support to NIH funded projects that are performing high-throughput broad based phenotyping of mouse knock-out (KO) lines (see RFA-RM-15-017) and to coordinate with international efforts so as to integrate all data into a common database under the auspices of the International Mouse Phenotyping Consortium (IMPC). The Data Coordination Center and Database (DCCDB) will perform the curation, analysis, visualization, and dissemination of the phenotype data from the knockout lines. Curation will require integration with other data sources. Analysis will require further development and validation of statistical methods. Visualization and queries will require innovative tools to disseminate the data in a real-time environment. The ultimate goals of these efforts are to enhance the ability of the biomedical research community to identify new disease models, to better understand phenotypic patterns, and to gain a more comprehensive understanding of the underlying function of each gene.
October 7, 2015
November 9, 2015
December 9, 2015, by 5:00 PM local time of applicant organization. All types of applications allowed for this funding opportunity announcement are due on this date.
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.
December 10, 2015
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
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
More than 12 years have passed since the completion of the Human Genome Project, yet we remain largely ignorant about the function of most genes in the mammalian genome. In fact, the function of at least half of the mammalian genes is poorly understood; nearly one third have no functional annotation. In 2011 it was reported that 75% of protein research continues to focus on the 10% of proteins that were known before the genome was sequenced. Barriers to understanding the function of ‘dark’ protein-coding genes include lack of tools and lack of funding mechanisms to support tool development and characterization. Defining the functional role of the complete set of protein-coding genes will have a transformative effect on biology and the understanding of human disease but cannot be achieved with the traditional hypothesis-driven research approach.
The mouse has long been an important mammalian model system for the study of gene function in human health and disease, and the premiere embodiment of that is the ability to generate knockout (KO) mice. Mouse mutants with phenotypes mimicking human traits are critical research tools for understanding the genetics underlying mammalian biology. Equally important, mouse mutants have been the tools used to begin to understand gene function and pathways as the field has moved from gene identification to mammalian functional genomics.
There have been a number of international efforts that worked to develop a comprehensive KO mouse resource. Following a March 2005 workshop which endorsed the concept (http://www.genome.gov/15014549), the NIH launched the Knockout Mouse Program (KOMP) to generate mutations in 8,500 genes in the C57BL/6 strain by deleting all or most of the exons in target genes or by making knockout-first conditional ready alleles. By the end of 2011, KOMP had completed the goal of producing 8,500 mutant ES cell lines. In parallel, the European Conditional Mouse Mutagenesis Program (EuCOMM) and the North American Conditional Mouse Mutagenesis Program (NorCOMM) accomplished their goals of producing an additional 9,000 mutant strains. The three programs coordinated their efforts through the International Knockout Mouse Consortium (IKMC) to produce a comprehensive resource of mutant mouse embryonic stem (ES) cell lines representing over 17,000 unique genes. In 2006, the NIH established a repository to archive, maintain, and distribute ES cell clones, as well as live mouse lines, frozen embryos and sperm, and vectors (www.komp.org). To date, the KOMP Repository has delivered over 31,000 products (vectors, ES cell lines, mice, and services) representing over 5,000 unique genes, which is a strong indication of the community’s valuation of the program.
The first large-scale phenotyping effort using IKMC ES cells was funded by the European Commission (EC) in 2008. The European Mouse Disease Clinic (EUMODIC, http://www.eumodic.org/) program was comprised of 4 mouse phenotyping centers, with the goal to provide phenotype information on 500 IKMC knockout mouse lines using a common phenotyping protocol developed by the European Mouse Phenotyping Resource of Standardised Screens (EMPReSS, http://empress.har.mrc.ac.uk/). The NIH held a KOMP Phenotyping Conference in Bethesda, MD in October 2009, at which a group of researchers representing diverse scientific backgrounds expressed their unanimous enthusiasm and support for a proposed effort to conduct high-throughput and comprehensive phenotyping of the resource being produced by the members of the IKMC (meeting report available at www://www.komp.org). The phenotyping data would be released rapidly and freely to the public as they are generated, with the mice being archived for distribution to the research community. The meeting participants stressed that any U.S. phenotyping effort must be coordinated with comparable efforts elsewhere (similar discussions and plans were being made in Europe, Canada, and Asia). The standard phenotyping tests, analyses, and examinations included in the KOMP resource effort should be chosen primarily on the basis of their reliability, power, and likelihood to reveal disease and human clinical relevance. These recommendations were highly similar to those that came from other efforts to solicit input from the US national research community.
Subsequently, the Knockout Mouse Phenotyping Program (KOMP2) was launched in the fall of 2011. Three mouse production and cryopreservation centers were funded and tasked with converting IKMC knockout ES cells into mice for phenotyping. These centers had the additional responsibility of making a preliminary determination of whether the null mutation affected the fertility or embryonic development of the mice. Three phenotyping centers were funded and assigned the task of broad based phenotyping. The funded centers were required to work together to identify a common set of core assays that were performed similarly across all centers using “harmonized” conditions. Presently, the KOMP2 research network has completed production of 2,500 strains, and is on track to complete the phenotyping project in the fall of 2016.
The final component of KOMP2 was the inclusion of the Data Coordination Center and Database (DCCDB) to track progress, perform quality control (QC) and other analyses on the phenotype data, and disseminate this information to the research community. The DCCDB project has two major functional units, a Data Coordination Center (DCC) and a Core Date Archive (CDA). The DCC serves as the interface between the mouse centers and the CDA, and performs tracking and QC functions. The CDA is the data warehouse and performs the curation, analysis, visualization, and dissemination of the data. The NIH-funded KOMP2 DCCDB supports the entire international consortium, operating the web portal to provide a single point of access to all data (http://www.mousephenotype.org). The DCCDB has accomplished its goal of presentation of phenotype data for knockout mouse strains (>2,000 lines to date), and also disseminates pre-QC data for additional strains. The ultimate goals of these efforts are to make available a physical resource of well-characterized KO strains and to distribute the associated genotyping and phenotyping data. The DCCDB makes associated data and metadata readily accessible, in order to support efforts to improve and enhance the rigor and reproducibility of biomedical research. Features that aid the community in data mining and utilization include highlighting mouse disease models that share phenotype features with human diseases with no known causative gene variant, and the ability to search the IMPC database by clinical human phenotype terms. In addition, based on strong NIH interest in sexual dimorphism in clinical and basic research, reporting for this is now available for all detected mouse phenotypes. It is expected that applicants to this FOA will coordinate closely with both the KOMP2 research network and the other members of the IMPC to select knockout lines to be phenotyped, harmonize phenotyping platforms, and continue data integration, analysis, and visualization, so as to enhance the utility and clarity of the IMPC-generated phenotyping data.
The purpose of this FOA is to solicit applications for a project to continue development and operation of the Data Coordination Center and Database unit of the KOMP2 research network. There will be several key activities or units needed to support the KOMP2 network:
Data Coordination Center: The DCC will serve as the interface between the mouse production and phenotyping centers and the data archive. It is expected that applicants will propose to work closely with the mouse production and phenotyping centers to facilitate data transfer, track data and metadata, and perform quality control. To that end, it will be necessary to develop a detailed understanding of workflows, data types, and data infrastructure at each center. The DCC must include the functionalities of a tracking database and a database management system to allow research network members and NIH staff to follow progress of projects in the pipeline, using a web based platform. It will be critical for production groups and NIH staff to be able to produce live reports of steps in the pipeline for tracking and monitoring purposes, e.g., to perform a query to identify languishing or incomplete projects. The applicant should propose a strategy to work with centers to maintain standard operating procedures (SOPs), with an end goal to transfer only fully standardized and quality controlled data into the CDA.
Core Data Archive: The core data archive will be a robust data repository that stores production and phenotype data, associated metadata, phenotype annotations, as well as other annotation data derived from external sources, and related gene function datasets. The CDA will provide data to a web portal and API interfaces for external users, and host tools or links to tools to manipulate and view data.
Data Analysis and Annotation: The DCCDB will perform annotation of the data, employing standard phenotype ontologies, in order to facilitate searches. It will be required to be able to perform statistical analysis using a variety of approaches to identify phenotypic outliers, and to provide statistical analysis software tools that are accessible to users. The DCCDB must provide the ability to perform complex queries, and provide visualization tools for images, 3D datasets, and quantitative data. It will be necessary to provide links to other databases and to further develop phenotype-matching algorithms for human diseases. Integration of data by building links to human disease databases and relevant genomics datasets is anticipated to enhance value to end users.
Web Portal: The web portal (currently hosted at www.mousephenotype.org) will provide a single point of entry to access KOMP2 and IMPC data for the biomedical community. Multiple data types will need to be displayed and tools will need to be made available to allow public access and the ability to visualize and query data.
Technology Development: The DCCDB will need to keep abreast of technology development and make efforts internally to improve the efficiency of the proposed project with respect to data handling, phenotype calling, QC, web portal improvements and integration with other large scale projects.
Marketing and Community Outreach: It is expected that the NIH will ask successful applicants to this FOA to coordinate their outreach efforts with the International Mouse Phenotyping Consortium (IMPC). This activity will include user training in person and by webinar. It will be important to work to advertise and expand the use of the web portal, data, and biologic resources by the broader scientific community.
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.
Renewal of applications submitted to RFA-RM-10-012
The OER Glossary and the SF424 (R&R) Application Guide provide details on these application types.
Issuing IC and partner components intend to commit an estimated total of $12,500,000 to fund one award.
Application budgets are not limited but need to reflect the actual needs of the proposed project.
The total project period may not exceed five years.
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.
Only the grantee funded under the KOMP2 Knockout Mouse Phenotyping Project Database (U54) is eligible to apply.
Non-domestic (non-U.S.) Entities (Foreign Institutions) are eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.
Applicant organizations 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.
This FOA does not require cost sharing as defined in the NIH Grants Policy Statement.
Only one application per institution (normally defined by having a unique DUNS number or NIH IPF number) is allowed.
The NIH will not accept duplicate or highly overlapping applications under review at the same time. This means that the NIH will not accept:
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.
All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed, with the following exceptions or additional requirements:
The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed.
All instructions in the SF424 (R&R) Application Guide must be followed, with the following additional instructions:
Research Strategy: The Research Strategy should consist of the following subsections, uploaded as a single pdf attachment.
A) Overall Goals Section:
Background: Describe the purpose and history of the DCCDB, the role it played within the KOMP2 program and IMPC, and its service to the biomedical research community. Describe overall design, structure, development and evolution of the DCCDB, including its management structure, integration of components and subcontracts. Describe what information, assistance and activities became available to the KOMP2 Production and Cryopreservation as well as Phenotyping centers and other IMPC members. The applicant should discuss their experience in defining and meeting milestones and goals for an information technology/database effort.
Plans for the Continued Operation and Maintenance of the DCCDB: Provide a general overview of the proposed center. Describe improvements and innovations that will enhance how the resources and data generated by the IMPC will be made available to the NIH-supported investigators and the biomedical research community. The plan must discuss the management plan as well as the software and hardware resources that are required. The application should include information on how efficient and unencumbered access to the DCCDB will be developed and maintained.
B) Data Coordination Center:
Data Exchange/Wrangling: Describe how the DCC will work with mouse production and phenotyping centers to accomplish tasks described in this section. For example, the applicant should describe a process to develop and track versions of SOPs. The data being tracked by the DCC should include, but are not limited to, a variety of information types relating to the status and results of phenotyping plans (from gene selection through to phenotyping of mice) and the locations of mice in publically funded repositories. The applicant should discuss processes to exchange this data with centers and repositories and processes to ensure data integrity. Describe requirements for and processes to transfer above data into a core data archive.
Project Tracking: Describe how the DCC will collect and compile data related to “phenotyping plans,” these plans being the gene-centric projects that encompass producing KO mice and phenotyping them. Describe how the DCC will collect and compile related data that may include availability and location of frozen embryos, sperm or mice, status in the mutation production and phenotyping pipelines, and derived data, such as calculations intended to identify incomplete projects. This functionality must allow complex queries of the project, not just gene-centric searches. Describe how the DCC will collect metadata, including a timestamp on all data sets, which will be vital to allow tracking of progress, identification of bottlenecks, incomplete steps, or languishing plans, and retrospective analysis of the projects. Describe methods to handle multiple allele designations generated by CRISPR/Cas9 or emerging technologies, as well as collect and maintain data on genotyping and microinjection experiments. It is anticipated that more complex genotyping, including identifying and tracking off-target mutations will be required.
Phenotype Data: Describe how the DCC will collect phenotype data. The Database and the DCC operations should be able to accommodate not only the KOMP2 project, but be able to continue the upload, QC and integration of data sets from other members of the IMPC to help reach the common international project goals. It is anticipated that multiple data types will be involved, including but not limited to numerical data, image data, graphical data representations and annotation of data. Describe how data will be QC’d, such as by using validation modules to prevent erroneous data from being uploaded to the Core Data Archive, and automated quality control tests to identify questionable data for further investigation by data experts and the originating phenotyping center.
Additional Data Sets: The application should address how the DCC and its operations will be able to accommodate not only the KOMP2 project but also be able to continue the upload, QC and integration of data sets from other members of the IMPC to reach the common international project goals. It is anticipated that the KOMP2/IMPC phenotyping will continue to add secondary and other more depth phenotyping assays that should wherever agreed by KOMP2 and external investigators be integrated or seamlessly linked to the core KOMP2 datasets.
C) Database, Web Portal, and Technology Development. The Database and Web Portal will provide the means to store, analyze, and disseminate the data. Specific functionalities are described in the following paragraphs.
Core Data Archive: Describe software and hardware architecture of a CDA capable of storing and serving a large, complex dataset. The CDA should provide information about the mice and germplasm resources, and facilitate the ability of researchers to obtain these materials. For phenotype data, it is anticipated that multiple data types will be involved, including but not limited to numerical data, image data, graphical data representations and annotation of data. It is anticipated that there could be the need for displays of Magnetic Resonance Image (MRI) data, Computed Tomography (CT) data, ultrasound, movies, histopathology images, Fluorescence-activated cell sorting (FACS) data, and the flexibility to include additional data types and phenotype tests in the future. The structure of the CDA should accommodate complex queries.
Data Access: Describe custom or adapted software tools for visualization and analysis that will be developed or are currently available, and the method for distribution. Describe API functionalities, and supporting documentation or training, that will be made available. A method of downloading large datasets from DCCDB should be included so that users can directly query and download all or large parts of the data.
Data Transfer: The DCCDB should describe the plan to transfer the contents of the database to a permanently funded data warehouse, including but not limited to NCBI. For example, it is anticipated that the DCCDB could work with NCBI to deliver data in formats appropriate for dbGaP (http://www.ncbi.nlm.nih.gov/gap).
Data Analysis: Multiple data types are collected in the KOMP2 Project, including numerical data (categorical and quantitative) and image data, as well as calculation-derived data. It is anticipated that there could be the need for analysis of MRI data, CT data, ultrasound, images, movies, histopathology, FACS, and the flexibility to include additional data types and phenotype test in the future. Describe the statistical tools for analysis of these various data types. It will be important to automatically identify statistically significant phenotypes and annotate them for every procedure and parameter that is feasible.
Data Integration: The efforts of the DCCDB should not duplicate the informatics efforts of other projects funded to describe the characteristics or functions of mouse genes. Certain useful external annotations should be presented on the IMPC web portal, such as synonyms and genome browser functions. Describe efficient and non-duplicative procedures to incorporate and make available this information. In addition, it will be important for the information in the DCCDB to be accessible to other such projects. Thus, the applicant also should describe how information from the DCCDB will be transferred or linked to other mouse informatics resources including, but not limited to, the UCSC Genome Browser, ENSEMBL, NCBI, and Mouse Genome Informatics, as well as emerging databases on human disease related genes.
Data Annotation: The annotation of data and the need for controlled vocabularies and structured ontologies will be needed to make the data accessible and comparable from different centers over the time of the project. Thus, the applicant should address the plans to accommodate such functionalities. Describe tools to support annotation of 2-D and 3-D image data. One requirement will be that the applicant follows the rules and guidelines established by the International Committee on Standardized Genetic Nomenclature for Mice.
Web Portal: The web portal (currently hosted at www.mousephenotype.org) will provide a single point of entry to access KOMP2 and IMPC data for the biomedical community. The application should describe the functionality of the interface that will allow searching by gene, phenotype, and disease terms including complex searches that allow users to “dial in” their precise multi-parameter searches. For example, a search to show all mice and/or targets that have a 20% increase in body weight, a 50% increase in lipid levels and 25% decrease in glucose. The searching features should allow users to select a significant number of parameters, define numerical ranges, and filter by % changes, or standard deviation or p-values. The user should be able to compare KO data with wild type controls or historical data.
Web Tools: There is a strong need for improved and innovative visualization tools for various data types. The application should address how to handle multiple data types and visualizations, including numerical data, image data, graphical data representations and annotation of data. Thus, the user interface and visualization tools must account for these data types and be adaptable for future improvements in data visualization and manipulation as suggested by KOMP2 members and the general scientific community. Describe a plan whereby viewing and manipulation of the data occurs for the most part with tools that are available freely.
Other Features: The application should describe how the web portal will include tools to access the primary data, compare different KO datasets, and provide tools to search and analyze the KOMP2 data with a variety of third party data on gene function, pathway analysis, and systems analysis. Describe other data display and analysis tools that may be required. The ability to integrate KOMP2 data with other gene function data and to allow and encourage third parties with unique perspectives on human disease, data mining and complex data analysis to utilize the KOMP2/IMPC will be a critical means to accomplish the goals of KOMP2 and key metric for the DCCDB. The DCCDB should explain how it plans to be responsive to the requests of NIH staff, KOMP2/IMPC centers, and the external user community to continue improvement and refinement throughout the project. The web portal should support all major platforms. The development of mobile apps is highly desirable.
Technology development: Describe plans for technology development efforts to improve the efficiency of the proposed project with respect to data handling, phenotype calling, QC, web portal improvements and integration with other large scale projects. Describe in detail how the technology development efforts will impact on the function of the whole KOMP2. Explain how technology development will synergize with other activities at KOMP2 beyond what can be achieved through a traditional software development. Describe the framework, design, resources used, methods and analyses, which should be adequately developed and integrated. The applicant should demonstrate that overall consortium input was solicited in deciding the goals of the technology development to improve the function of the entire KOMP2.
D) Management and Communication Plan:
Internal: The application should describe a management plan commensurate with the complexity of this effort, including integration of the separate components, key personnel, section leaders and internal reporting relationships and mechanisms for reporting progress to NHGRI and ORIP/DPCPSI (see Terms and Conditions, below) as well as the decision-making process. Include how this management plan will support the achievement of the proposed goals and milestones of the project. The proposed management plan should ensure appropriate prioritization of activities, including course corrections when needed, and should describe how problems will be identified and resolved, should encourage and provide training for personnel, and visibility and effectiveness of the efforts. The management plan should discuss past experiences working in large collaborative data production projects of a degree of complexity similar to what is being requested.
Coordination and Communication: The application must describe a plan to support, facilitate and coordinate communication and provide data to various meetings and sub-committees within the KOMP2 network and the IMPC. The DCCDB will have an important role in participating and contributing to the KOMP2 and IMPC focus groups and subcommittees. Describe how the DCCDB will support and, where needed, organize, various working groups’ teleconferences to discuss data, SOPs, QC and new developments. The PD/PI and other key personnel are required to attend the annual KOMP2 and IMPC meetings, as well as meetings of the focus groups. Staff should be assigned to record the IT requirements for presentations when discussed, and work closely with the other KOMP2 centers to fulfill those needs. The DCC will post submitted meeting minutes and reports to the appropriate directory, notifying the KOMP2 members when minutes become available. The center should actively participate in the KOMP2 and IMPC program evaluation activities including progress reports, site visits, and providing additional communication and materials to the NIH as needed.
Marketing Plan: The DCCDB should present an effective marketing program, aimed at increasing the awareness of the scientific community regarding KOMP2, and generating a plan to identify and recruit additional entities who could potentially contribute to the created databases. It is also incumbent on the DCCDB to assist the wider community to effectively access and use data created by KOMP2 resources, conduct additional analyses and apply for grants for secondary deep phenotyping, and where desirable incorporate these additional datasets with the database. The development of new marketing methods based upon evaluation of researcher interest via surveys and methods to analyze interactions with the user interface is highly encouraged. Describe methods for development of additional methods to raise visibility of resources available from the KOMP2, including social media, targeted publications, and development and implementation of a resource tagging system is also encouraged.
Community Outreach: The DCCDB will also develop a plan to provide community training to enhance the use and utility of the web portal by the user community. Seminars, presentations, posters and workshops should be an element of this effort. The DCCDB should implement mechanisms that solicit regular feedback and opinion from the user community, including comment boxes and online flash-surveys, and then regularly analyze the results. The DCC will also track and report to NIH, users numbers, web hits and traffic as well as assist in other tracking metrics (such as mice and publications).
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:
Appendix: Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Planned Enrollment Reports as described in the SF424 (R&R) Application Guide.
When conducting clinical research, follow all instructions for completing Cumulative Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.
Foreign (non-U.S.) institutions must follow policies described in the NIH Grants Policy Statement, and procedures for foreign institutions described throughout the SF424 (R&R) Application Guide.
See Part I. Section III.1 for information regarding the requirements for obtaining a Dun and Bradstreet Universal Numbering System (DUNS) Number and for completing and maintaining an active System for Award Management (SAM) registration. Part I. Overview Information contains information about Key Dates. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission.
Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date. If a Changed/Corrected application is submitted after the deadline, the application will be considered late.
Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.
Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.
This initiative is not subject to intergovernmental review.
All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.
Pre-award costs are allowable only as described in the NIH Grants Policy Statement.
Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.
Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.
For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues.
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 NOT-OD-13-030.
Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).
Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.
Does the project address an important problem or a critical barrier to progress in the field? If the aims of the project are achieved, how will scientific knowledge, technical capability, and/or clinical practice be improved? How will successful completion of the aims change the concepts, methods, technologies, treatments, services, or preventative interventions that drive this field? In addition to the standardized criteria above, the following will be evaluated as part of the Significance score. Does the center address the needs of investigators in a variety of research areas rather than in a single or few areas? Will the project resources be available to investigators on a local, regional, national, and international basis?
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the project? If Early Stage Investigators or New Investigators, or in the early stages of independent careers, do they have appropriate experience and training? If established, have they demonstrated an ongoing record of accomplishments that have advanced their field(s)? If the project is collaborative or multi-PD/PI, do the investigators have complementary and integrated expertise; are their leadership approach, governance and organizational structure appropriate for the project? In addition to the standardized criteria above, the following will be evaluated as part of the Investigator(s) score. Are the PD(s)/PI(s) appropriately trained and well suited to manage such a large and diverse project?
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? In addition to the standardized criteria above, the following will be evaluated as part of the Innovation score. Are the overall designs of the DCCDB innovative? Does the application utilize innovative approaches to collect and provide rapidly to the biomedical community data and resources generated by the project?
Are the overall strategy, methodology, and analyses well-reasoned and appropriate to accomplish the specific aims of the project? Are potential problems, alternative strategies, and benchmarks for success presented? If the project is in the early stages of development, will the strategy establish feasibility and will particularly risky aspects be managed? In addition to the standardized criteria above, the following will be evaluated as part of the Approach score. Are the organization, management structure, integration of the components, key personnel and reporting relationships well described and appropriate? Does the project description demonstrate that production/cryopreservation and phenotyping activities are well integrated within KOMP2? Are adequate approaches proposed for enhancement of the capacity or research direction to utilize innovative technologies, and improve the efficiency of collecting, storing and analyzing the data?
If the project involves human subjects and/or NIH-defined clinical research, are the plans to address 1) the protection of human subjects from research risks, and 2) inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion or exclusion of children, justified in terms of the scientific goals and research strategy proposed?
Will the scientific environment in which the work will be done contribute to the probability of success? Are the institutional support, equipment and other physical resources available to the investigators adequate for the project proposed? Will the project benefit from unique features of the scientific environment, subject populations, or collaborative arrangements? In addition to the standardized criteria above, the following will be evaluated as part of the Environment score. Is there appropriate institutional support for the project, and are plans for continuity appropriate for the scientific field’s needs? Is the form of this commitment (space, resources) appropriate? Is there evidence of project participation in coordination and integration of its activity with other KOMP2 centers as well as other members of IMPC?
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.
Review Criteria for Data Coordination Center
The DCC Section will receive an overall merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following items:
Review Criteria for Core Data Archive
The CDA Section will receive an overall merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following items:
Review Criteria for Data Analysis and Annotation
The Data Analysis and Annotation Section will receive an overall merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following items:
Review Criteria for Web Portal
The Web Portal Section will receive an overall merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following items:
Review Criteria for Marketing Activity and Community Outreach
The Marketing Activity and Community Outreach Section will receive an overall merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following items:
Review Criteria for Technology Development
The Technology Development Section will receive an overall merit descriptor (outstanding, acceptable, unacceptable) based on consideration of the following 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.
For Renewals, the committee will consider the progress made in the last funding period.
As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.
Reviewers will assess whether the project presents special opportunities for furthering research programs through the use of unusual talent, resources, populations, or environmental conditions that exist in other countries and either are not readily available in the United States or augment existing U.S. resources.
Reviewers will assess the information provided in this section of the application, including 1) the Select Agent(s) to be used in the proposed research, 2) the registration status of all entities where Select Agent(s) will be used, 3) the procedures that will be used to monitor possession use and transfer of Select Agent(s), and 4) plans for appropriate biosafety, biocontainment, and security of the Select Agent(s).
Reviewers will comment on whether the following Resource Sharing Plans, or the rationale for not sharing the following types of resources, are reasonable: 1) Data Sharing Plan; 2) Sharing Model Organisms; and 3) Genomic 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 National Human Genome Research Institute, in accordance with NIH peer review policy and procedures, using the stated review criteria. Assignment to a Scientific Review Group will be shown in the eRA Commons.
As part of the scientific peer review, all applications:
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 Advisory Council for Human Genome Research Institute. The following will be considered in making funding decisions:
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:
Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current HHS, PHS, and NIH policies.
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The Project Scientist will:
Areas of Joint Responsibility include:
All components of the KOMP2 program will be funded by cooperative agreements and a single Steering Committee and a single Panel of Scientific Consultants will serve for all of the KOMP2 activities. The Steering Committee will serve as the main governing board of the KOMP2 Research Network. The Steering Committee membership will include the P.I. of each awarded cooperative agreement and the NIH Project Scientist of each of the components of the KOMP2 Research Network. Additional members may be added by action of the Steering Committee. Members of the KOMP2 Working Group may attend the Steering Committee meetings. Government employees outside of KOMP2 Working Group members may also attend, if their expertise is required for specific discussions.
The Steering Committee will:
Each full member will have one vote; the total votes of the NIH Project Scientist-members of the Steering Committee will constitute a minority of the votes. Awardee members of the Steering Committee will be required to accept and implement policies approved by the Steering Committee.
Panel of Scientific Consultants:
This program will be coordinated with and be a member of the IMPC. The IMPC and KOMP2 shall convene a joint Panel of Scientific Consultants (PSC). The PSC will be responsible for reviewing and evaluating the progress of the members of the KOMP2 Research Network toward meeting their individual and collective goals. The PSC will provide recommendations to the KOMP2 Working Group and the Directors of the all other participating institutes, about continued support of the components of the KOMP2 Research Network. The Panel will be composed of four to six senior scientists with relevant expertise who are not P.I.s of a cooperative agreement involved in the KOMP2 Research Network. The membership of the Panel of Scientific Consultants may be enlarged permanently, or on an ad hoc basis, as needed.
The Panel of Scientific Consultants will meet at least once a year and by conference call 2 to 3 times per year. During part of this meeting, there will be a joint meeting with the Steering Committee to allow the PSC members to interact directly with the awardees. Annually, the PSC will make recommendations to the NIH regarding progress of the KOMP2 Research Network and present advice about changes, if any, which may be necessary in the KOMP2 Research Network program to the relevant NIH Directors.
The KOMP2 Working Group consists of program staff from each of the NIH institutes supporting the KOMP2. The purpose of the KOMP2 Working Group will be to disseminate information about the progress of the KOMP2 Research Network to the participating Institutes and to provide a forum for the participating Institutes to discuss issues related to KOMP2. The KOMP2 Working Group members will report to the Director of their respective IC.
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 regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.
When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Commons Help Desk (Questions regarding eRA Commons
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problems that threaten submission by the due date, post submission issues)
Finding Help Online: https://grants.nih.gov/support/ (preferred method of contact)
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Email: GrantsInfo@nih.gov (preferred method of contact)
Colin Fletcher, Ph.D.
National Institute of Human Genome Research (NHGRI)
National Human Genome Research Institute (NHGRI)
Telephone: (301) 496-7531
National Human Genome Research Institute (NHGRI)
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.
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