and Human Services (HHS)
EXPIRED
Participating Organization(s) |
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/). The FOA will be administered by the National Human Genome Research Institute (NHGRI), http://www.genome.gov/ on behalf of the NIH Office of Strategic Coordination (Common Fund) |
|
Funding Opportunity Title |
Library of Integrated Network-Based Cellular Signatures (LINCS): Perturbation-Induced Data and Signature Generation Centers (U54) |
Activity Code |
U54 Specialized Center- Cooperative Agreements |
Announcement Type |
New |
Related Notices |
|
Funding Opportunity Announcement (FOA) Number |
RFA-RM-13-013 |
Companion Funding Opportunity |
None |
Catalog of Federal Domestic Assistance (CFDA) Number(s) |
93.310 |
Funding Opportunity Purpose |
This FOA seeks to establish a large-scale data production effort to systematize approaches for identifying mechanism-based associations between the effects of disparate biological perturbations, by means of signatures. Such perturbations may include siRNAs, small bioactive molecules, environmental manipulations, among others. These data will also inform a knowledge base that can be used to study functional relationships among the responding cellular components. The Library of Integrated Network-Based Cellular Signatures (LINCS) program will support high-throughput collection and integrative computational analysis of informative molecular activity and cellular response features applied to a set of carefully selected human cell types. Relevant predictive patterns of molecular activities and other cellular behaviors are the cellular signatures that characterize responses to a variety of perturbing agents. The resulting knowledge-base of signatures will form the basis of a long-lived resource that can be used broadly by the community. For example, LINCS may inform the association of disease states with detailed molecular or cellular phenotypes caused by specific genetic variants, relating disease with changes in the function of specific gene networks, or the mechanism of action of known drugs. This FOA seeks to fund large-scale data production efforts that will enhance the existing LINCS resource while addressing the following: use of a broader range of cell types and assays than used in the existing LINCS resource, improved multidimensional data integration, some new technology development, user-interfaces needed by the typical biomedical scientist, and dissemination of the LINCS approach to study a broad range of disease biology and mechanisms. The outcomes of the research solicited by this FOA are expected to be highly synergistic with those of other research programs. |
Posted Date |
August 19, 2013 |
Letter of Intent Due Date(s) |
November 19, 2013 |
Application Due Date(s) |
December 19, 2013 |
AIDS Application Due Date(s) |
Not Applicable |
Scientific Merit Review |
March 2014 |
Advisory Council Review |
May 2014 |
Earliest Start Date |
July 2014 |
Expiration Date |
December 20, 2013 |
Due Dates for E.O. 12372 |
Not Applicable |
Required Application Instructions
It is critical that applicants follow the instructions in the PHS 398 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. While some links are provided, 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.
Looking ahead: NIH is committed to transitioning all grant programs to electronic submission using the SF424 Research and Related (R&R) format and is currently investigating solutions that will accommodate NIH’s multi-project programs. See NOT-OD-13-075 and NIH’s Applying Electronically website for more information.
Part 1. Overview Information
Part 2. Full Text of Announcement
Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission
Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information
This 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 Library of Integrated Network-Based Cellular Signatures (LINCS) program was established in 2010 to create a network-based understanding of biology by cataloging, analyzing, and integrating informative molecular activity and cellular feature signatures generated in a number of biological processes in a range of cell types in response to a variety of perturbing agents. LINCS supports high-throughput collection and integrative computational analyses of these cellular signatures and makes them available to the research community (http://lincsproject.org).
The purpose of this funding opportunity announcement (FOA) is to establish 3-5 LINCS Data and Signature Generation Centers (DSGC) to generate perturbagen-response data, produce relevant cellular signatures from these data, and make these data and signatures available to the research community. Each DSGC will work collaboratively with other components of the LINCS program to ensure that data, signatures, and analytical tools are annotated and integrated within the LINCS consortium. Each DSGC will also have a significant community interaction component. This will include (1) demonstrating the utility, for and by the wider scientific community, of the proposed DSGC resource; (2) identifying other research efforts generating compatible perturbagen-response data to incorporate into the LINCS resource; and (3) supporting data integration activities by maximizing the synergies obtained by overlapping cell types and perturbations among the different DSGCs that make up part of the LINCS consortium. Each DSGC will work actively with a Data Coordination and Integration Center (which will be solicited separately) to enable the LINCS consortium to provide a single, uniform method for community access to all LINCS resources and tools.
The underlying premises of LINCS are that disrupting any one of the many steps of a given biological process will cause changes in the molecular composition, cellular characteristics, behavior, and/or function of cells (i.e., the cellular phenotype); that these changes can be globally characterized in a variety of cellular assays; that the resulting datasets will allow insightful comparisons to be made between the disease state and cellular states produced by other perturbations; and that doing so will lead to novel mechanistic information in basic cell biology and about diseases and their remediation or prevention. Observing how and when a cell’s phenotype is altered by specific perturbations can provide clues about the underlying mechanisms involved in cellular biology and behavior, and ultimately, in disease. Therefore, a systematic collection of high-throughput (including omic ) responses to perturbations on a broad range of cell types is anticipated to lead to a resource that can be used to make substantial progress in the development of a network-based understanding of cellular functions and responses, which in turn should have a transformative impact on human disease and new approaches to drug discovery.
The pilot phase of the LINCS program has already substantiated many of these expectations. In the pilot phase of the LINCS program from 2010 - 2013, the principal task of the pilot LINCS centers was to develop a limited, yet coherent, data and signature resource that could be used by the general research community. The LINCS pilot phase was also intended to identify key issues in data annotation, integration, and analysis. There were three linked initiatives in the pilot: (a) for data and signature generation (RFA-RM-10-003), (b) development of new high-throughput assays to detect perturbation-induced cellular signatures (RFA-RM-10-004), and (c) novel computational methods for integrative data analysis (RFA-RM-10-005). The pilot effort of the program was evaluated with respect to feasibility of data production (considering both cost and throughput), the quality and scientific utility of such data and signatures, and the potential to develop into a more comprehensive program. The resources, data, and tools developed during the pilot program are available at http://lincsproject.org. With the success of the LINCS pilot phase, this FOA now solicits applications that will enhance and expand the LINCS program into a more valuable scientific resource for exploring the molecular processes and activities of cells.
To realize the goal of informing a network-based understanding of cellular functions and responses, the LINCS program plans to expand the scope and richness of cellular responses to be measured (assays used in the pilot phase continue to remain important and relevant if scientifically justified). The LINCS resource (and the resulting data matrix) has three dimensions: cell types, perturbations, and assay types. The existing resource is necessarily limited in scope by its pilot nature. This FOA seeks to catalyze research across a wider and more diverse scientific scope by supporting the addition of a broader and more informative range of cell types, perturbations, and measurements. There are multiple assay technologies currently available and in development that could increase the impact and utility of the LINCS resource.
If successful, the LINCS program will inspire researchers not supported by LINCS program funds to use the LINCS-generated knowledge to inform and accelerate their own research programs on diverse biological and disease-related problems. For this goal to be successful, the resources generated by the LINCS program should have broad impact and substantially improve our understanding of multiple diseases, organ systems, and basic biology. Thus each DSGC must address three essential aspects: Data Generation, Data Analysis and Signature Identification, and Community Interactions and Outreach.
A. Data Generation: Data generation in LINCS in the pilot phase is in a mid-to-high throughput mode, with a high degree of reproducibility achieved. It is expected that Data Generation by the DSGCs will be at scale (see section A5 below for what is expected of a high- or medium-throughput assay that is appropriate for LINCS in terms of the amount of data produced in a given unit of time), as this is essential for LINCS. To achieve the necessary scale, it is expected that all applicants to this FOA will be at their full production rate for data and signatures no later than the end of the first grant year.
To meet its data generation goals, the LINCS program will need to effectively leverage data that is already available in the public domain (including data from the LINCS pilot, http://lincsproject.org) by carefully balancing the type and scale of data that will be generated in the future.
Relevant analytical or technical pipelines for access to cells and other necessary reagents should be in hand or readily available so that data generation metrics can be achieved. Similar considerations apply to any analytical pipelines that convert raw data to processed data (see the next component for signature generation). Algorithms that are used for data processing should also, as relevant, be made publicly accessible. Useful data and metadata standards are crucial for generating signatures that can be utilized by the community and for addressing data integration challenges. An important goal of the LINCS program is to promote a culture where a large body of annotated and shareable data and analytical tools is available online for use by the broad biomedical research community. The development (if necessary) and use of data and metadata standards are critical for achieving this goal. Specifically, the following key elements should be kept in mind.
A1. Cell Types: The LINCS program intends to continue its current focus on human cells, specifically cell lines, primary tissue, iPS cells and their differentiated derivatives, and other relevant cell types. To maximize the utility of the LINCS resources, NIH anticipates that, during the course of the project period, community interactions will contribute to the specific choices made for the cell types. It is expected that these choices may be constrained by specific assay requirements (e.g., growth and quantity required for any needed culture conditions). Careful experimental design is crucial in creating a community LINCS resource and as such, in all cases, the choice of assays, cell types, and perturbations should follow an experimental design that balances considerations of scientific value, cost, pre-existing community data, and reagent availability.
A2. Perturbagens: The primary perturbations used in the LINCS pilot phase have been small molecules, growth factors, and genetic (knockdown or up-regulation by gene overexpression) perturbations. Given the overall goal of generating a network-based understanding of cellular systems in health and disease, these perturbations will continue to remain an important focus in this next phase of LINCS. However, applicants may propose other perturbations, such as disease (e.g., via iPS cells and their differentiated derivatives obtained from patients), viral infections, or environmental perturbations. As with cell types, the choice of perturbations (including dose, time-course, or combinations) undertaken within the LINCS program should leverage existing publicly available data, including data from the LINCS pilot. Applicability and utility for the broadest possible group of biomedical researchers are the goals of the LINCS program.
A3. Assays: The goals of the LINCS resource lead to certain necessary choices for the types of assays that can be scientifically useful. These (1) include a focus on high or medium throughput assays including hypothesis-free assays that broadly profile cellular responses and can include multi-parametric and multiplex assays, (2) should measure responses that are likely to be broadly and immediately useful to a large diversity of diseases or biologies, (3) should be flexible and amenable to work on multiple cell types, (4) should be relatively straightforward to replicate with a high level of QA/QC under standard operating procedures (SOPs) so that they may be easily adopted by other laboratories. Finally NIH anticipates that assays that may not have broad immediate applicability may still have a role within the LINCS data matrix. For instance, potentially useful targeted assays might include assays that are likely to substantially enhance the interpretation of data from other broadly usable assays or that complement those that exist already in the LINCS database or other community resources.
A4. Filling the LINCS data matrix: As it is not possible to completely populate the LINCS data matrix [cell types, perturbation, and assay types], informed choices must be made to ensure that LINCS centers generate data and signatures that will be maximally informative and useful. Certain choices of cell types, perturbations, and assays will result in a project that can cost-effectively and usefully populate the LINCS data matrix, while others will make a smaller contribution to increasing the value of the LINCS data matrix as a community resource. The applicant should provide scientific and pragmatic rationale for the proposed data generation plan and should explicitly address how the choices made relate to all three axes of the LINCS data matrix. An important element of the LINCS program’s goals includes data integration with other community resources. As such, choices about cell types, perturbations, and assays that will complement the large amounts of data that are being generated and made publicly available via the LINCS pilot and by other relevant projects (such as GTEx, Molecular Libraries, MAPGen, Epigenomics, Metabolomics, or Tox21) are important scientific considerations. It is expected that, once the DSGCs are funded, all of the PD(s)/PI(s) will participate in developing a plan to maximize synergies from sharing the cell types and perturbations used at the different centers.
A5. Scale of Data Generation: The LINCS program’s goals are to generate hundreds of thousands of data points and a significant number of signatures per year, once all combinations of cells and perturbations at different doses/time-points have been counted. This implies that sufficient resources will have to be allocated to all aspects that make the LINCS resource viable including data generation, processing and analyzing the data, generation and reproducibility of signatures, and enabling community access to the resources.
A6. Laboratory Technology Development: As this FOA will support awards for up to six years, we recognize that some assay technology development may be necessary to ensure that the assays continue to be maximally informative and cost effective. Thus, some technology development is permitted during the first three years of the award. It is expected that this technology development will not be a major thrust of the research activities within the award and will not exceed $200,000 in direct costs in any year. The goal of any such technology development would be to ensure that at the end of the first three-year period, the applicant can propose any changes to their data generation capabilities that may be necessary for scientific, programmatic, or for cost reasons, as determined by the DSGC’s midcourse review (see below). Thus, the technology development proposed should focus primarily on the further development or refinement of the assays proposed in this application. Minor refinements of new technologies that are sufficiently advanced (but not being proposed to be used within the DSGC) are also permissible. Applications should carefully justify the time and duration for technology development projects. Applicants are expected to establish suitable milestones and identify the approaches that would enable improvements in the technology.
B. Data Analysis and Signature Generation: This is an important component of this FOA and applicants are expected to devote roughly equal effort to data generation and data analysis. An important goal of the LINCS program is to build meaningful, generalizable signatures with sufficient predictive power and/or broad applicability from the assays that make up one axis of the LINCS data matrix. Algorithmic work that would lead to improved signatures is an important scientific goal. The LINCS program aims to create a single user interface for all of the LINCS resources for all biomedical researchers, including computational biologists. This single user-interface will be organized and established by a future Data Coordination and Integration Center (DCIC) that will be separately solicited.
B1. Data Storage: One of the scientific goals of the LINCS resource is to maintain a distributed data resource and not build a monolithic database. As such, each DSGC will build an appropriate database and an underlying infrastructure to support queries and other analytical requirements on the datasets being proposed by the DSGC. It is expected that queries and other analytical requirements of the community will be routed to the DSGC database/resource via the DCIC.
B2. Signature Generation: Given the scientific aims of the LINCS program it would be necessary to support a robust pipeline to handle large-scale data generation and cleanup, and capability for handling data and experimental QA/QC all the way from raw data to generating valid signatures. NIH anticipates that novel algorithms that generate more informative or predictive signatures will be developed throughout the entire project period. These could include algorithms that better handle noise in the data or that incorporate signatures from multiple assay systems, or algorithms that better integrate data to generate more reliable signatures.
B3. Tools for Community Access: NIH anticipates that each DSGC will develop novel approaches for the community to visualize, browse, and query the data and signatures for all data and signature types the DSGC proposes to generate. Data visualizations and tools that generate explanations (e.g., for summaries of the content of the database), as well as others that are primarily focused on exploratory analysis, are important components of interacting with the LINCS data matrix. Scientific challenges include adopting relevant software design (including API design) principles so that the DCIC can effectively deploy and use the computational and visualization tools built by the DSGC or depending upon user feedback adopt one or a few as core tools.
B4. Access by the DCIC: A crucial component of the DSGC s responsibility is to enable the LINCS Consortium to provide unified access to the user community through a web portal or by other methods. The user community is expected to encompass both typical biomedical researchers and expert computational scientists, each of whom has different needs and requirements for data and signature access. As indicated above, this unified LINCS access will be developed by a future DCIC, to be solicited in a separate FOA. Therefore the DCIC should be able to enable a LINCS user to execute a query on the entire LINCS matrix, which the DCIC would support by executing queries simultaneously on the local data in all DSGCs and then building a coherent representation of the results. Obviously this puts some constraint on the range of software and other choices for each DSGC, e.g., the DSGC may need to develop a number of core simple visualization elements that can be used under different conditions.
B5. General Considerations: An essential feature of accessibility to all of LINCS data and resources is adequate annotation and documentation. Metadata annotation for both data and software resources is crucial to fully realizing LINCS as a community resource.
B6. Community Access: Innovative solutions are needed for the entire biomedical community in the area of data provenance. One of the goals of the LINCS program is to introduce creative solutions (e.g., to enable easy access to all of the underlying data and tools that were used to generate specific tables or figures in publications). The DSGC should aim to facilitate this or other types of innovative methods that would enable data provenance goals.
C. Community Interactions and Outreach:
C1. Access to Bench Scientists: As mentioned above, access to and utilization of the LINCS resource by bench scientists is one of the major aims of the LINCS program. The LINCS pilot experience has identified the necessity for a single unified access to all LINCS resources. Therefore, in this phase of the LINCS program, such a unified access will be the primary responsibility of the (separately solicited) DCIC initiative within the LINCS program. To enhance the utility of the LINCS approach, NIH anticipates that training seminars, webinars, workshops, or challenges will be part of a DSGC.
C2. Access to Computational Scientists: Access should be provided to computational scientists that will support the development of new types of analyses, building and validating improved algorithms for signature generation, building cell-type specific biological networks, or any other use of LINCS resources. Creative solutions, either cloud-based or other data access alternatives dictated by the size and complexity of the datasets, are encouraged. Careful thought should be given to any special obstacles that might be faced and options to address them, such as very large data size that may make downloading multiple copies of datasets impractical. Approaches like workshops, hackathons, or challenges could be useful in creating an active computational community.
C3. Facilitating the Import into LINCS of Related Data Types from External Sources: It is expected that each DSGC will act as an active resource for its chosen data type(s) within the LINCS program. As such, each DSGC is expected to not only generate data and signatures for its data type for LINCS, but also to identify high quality, relevant non-LINCS data sets that might be incorporated into LINCS. Inclusion of such external resources will help connect LINCS to other research efforts. Examples for gene expression data that the applicant may propose might be a suitable subset of GEO as a source relevant for non-LINCS gene expression data or ImmGen for gene expression in the immunological system. Successful DSGCs will not only generate high quality and useful data and signatures to LINCS, they will become a scientific focus of such perturbagen-response data for the larger community. NIH anticipates that effective collaboration within the consortium and community engagement outside of the consortium will be a necessary ingredient for the overall success of the LINCS program. The future DCIC (see above) will have the primary responsibility for incorporating these outside datasets into the LINCS resource. Further details about the DCIC interaction can be found in Section IV.
C4. Community Interaction Projects: As another approach for the proposed DSGC to interact with the community and broaden its impact, LINCS will support Community Interaction Projects. These projects are intended to facilitate the dissemination of the LINCS approach in specific and challenging research areas in conjunction with researchers in that specific community through collaborative research. Community Interaction Projects may be hypothesis-driven, and it is expected that the resulting data and signatures would be made publicly available to the research community. Some examples of topics may include, but are not limited to, the following:
D. Program Administration
D1. Program Formation and Governance: Relevant personnel (including the PD(s)/PI(s)) from the DSGCs and other components of the LINCS Consortium will be expected to meet in person at least three times during the first year of the award to discuss, identify, and implement common data and software annotation and interoperability practices. It is expected that all DSGCs will be able to provide example data, signatures, and tools for the LINCS DCIC by the time that it is funded in December 2014. The LINCS Consortium will establish working groups to address specific issues, and all DSGCs should expect to be active participants in them.
D2. Data Sharing under this Initiative: As the LINCS program is generating a public resource, it is expected that all data and signatures will be released to the public via the DCIC within 3 months of generation or as soon as they are verified, cleaned and processed, whichever occurs first. It is expected that a quarterly public data release plan would be developed by all LINCS DSGCs.
D3. Mid-Course Review (undertaken around July 2017): LINCS centers will be subject to an administrative mid-course review. This review will assess the productivity of the center to date, its collaborations within the LINCS consortium to support data integration and integrated analysis in particular biological or disease-based applications, the use and adoption of its data by the greater research community, and the effectiveness of its community outreach. This midcourse review will also provide the DSGCs an opportunity to summarize results of any technology development efforts and to propose refinements to their proposed activities for the remainder of the project period. The NIH will determine funding levels for each center past 2017 based, in part, on the results of the mid-course review.
Funding Instrument |
Cooperative Agreement: A support mechanism used when there will be substantial Federal scientific or programmatic involvement. Substantial involvement means that, after award, NIH staff will assist, guide, coordinate, or participate in project activities. |
Application Types Allowed |
New The OER Glossary and the PHS 398 Application Guide provide details on these application types. |
Funds Available and Anticipated Number of Awards |
The NIH Common Fund intends to commit approximately $10,000,000 in FY 2014. Four to five (4-5) awards are anticipated in fiscal year 2014, contingent upon availability of funds and receipt of a sufficient number of meritorious applications. |
Award Budget |
Direct costs are limited to a maximum of $1.7M in each year. |
Award Project Period |
The maximum project period is 6 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.
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
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 not allowed.
Applicant Organizations
Applicant organizations must complete and maintain the following registrations as described in the PHS 398 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 and should work with their organizational officials to either create a new account or to affiliate an existing account with the applicant organization’s eRA Commons account. 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 PHS 398 Application Guide.
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.
NIH will not accept any application that is essentially the same as one already reviewed within the past thirty-seven months (as described in the NIH Grants Policy Statement), except for submission:
Applicants are required to prepare applications according to the current PHS 398 application forms in accordance with the PHS 398 Application Guide.
It is critical that applicants follow the instructions in the PHS 398 Application Guide, 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.
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:
Jennie Larkin, Ph.D.
Division of Cardiovascular Sciences
National Heart, Lung, and Blood Institute
6701 Rockledge Drive Rockledge 2, Room 8200
Bethesda, MD 20892-7940
Telephone: 301-435-0513
Fax: 301-480-1454
Email: [email protected]
Applications must be prepared using the PHS 398 research grant application forms and instructions for preparing a research grant application. Submit a signed, typewritten original of the application, including the checklist, and five signed photocopies in one package to:
Center for Scientific Review
National Institutes of Health
6701 Rockledge Drive, Room 1040, MSC 7710
Bethesda, MD 20892-7710 (U.S. Postal Service Express or regular mail)
Bethesda, MD 20817 (for express/courier service; non-USPS service)
All page limitations described in the PHS 398 Application Guide and the Table of Page Limits must be followed, in addition to the following page limitations to the Research Strategy section of each component of the application.
The following section supplements the instructions found in the PHS 398 Application Guide, and should be used for preparing a multi-component application.
The application should consist of the following components:
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.
Face Page (Overall)
All instructions in the PHS 398 Application Guide must be followed.
Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Overall)
All instructions in the PHS 398 Application Guide must be followed.
Table of Contents (Overall)
All instructions in the PHS 398 Application Guide must be followed.
Detailed Budget for Initial Budget Period (Overall)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide the total budget for the initial budget period for the entire Center application, by summing the individual budgets of each of the components (Data Generation, Data Analysis & Signature Generation, Community Interactions and Outreach, and Administration, including sub-contracts); i.e., the budget presented in the Overall Component should be the cumulative budget for the entire LINCS DSGC Center.
Budget for Entire Proposed Period of Support (Overall)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide the total budget for the entire proposed budget period for the entire Center application, by summing the individual budgets of each of the components (Data Generation, Data Analysis & Signature Generation, Community Interactions and Outreach, and Administration, including sub-contracts); i.e., the budget presented in the Overall Component should be the cumulative budget for the entire LINCS DSGC Center.
Biographical Sketch (Overall)
All instructions in the PHS 398 Application Guide must be followed.
Resources (Overall)
All instructions in the PHS 398 Application Guide must be followed.
Research Plan (Overall)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Specific Aims: The Specific Aims for the Overall Component should be the overall vision for the Center. These Specific Aims should not be the same as the specific aims of the other components, but should be overarching and at a high level.
Research Strategy: The Overall Component should provide a concise vision and proposed plan for the Center. What scientific challenges are being addressed, what approaches, methods, software, and tools will be generated, who are the users, and how will the Center be useful? The Overall Component should also include a concise description of the structure of the Center, including a brief management plan and organization chart.
The Overall Component should explain how the individual components of the center including key personnel, will interact. Clearly explain the guiding principles of the interaction, including software design activities, with the LINCS-BD2K Data Coordination and Integration Center and other community interaction efforts.
Protection of Human Subjects: Any sections relating to Human Subjects for the entire application should be placed here.
Vertebrate Animals: Any sections relating to Vertebrate Animals for the entire application should be placed here.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide, with the following modifications:
The resource sharing plan for the Overall Component should cover all the activities of the Center. Program Staff may negotiate modifications to these plans prior to funding. Plans are expected for sharing software (see below).
Consistent with achieving the goals of the program, NIH expects that the project datasets, experimental protocols including Standard Operating Procedures (SOPs), as relevant, model and software be widely shared with the scientific community for research, as much as possible. LINCS awardees are expected to release to the research community data, experimental protocols, models, and software in a timely fashion through an informatics platform and other standard mechanisms. It is expected that raw data, as well as processed data along with relevant signatures be made available to the community, as appropriate, via existing public databases or specialized resources generated for this project. The development of policies, methods, and standards for such sharing are critically important for LINCS. The NIH expects that the LINCS awardees will develop such policies, methods, and standards in concert with the NIH and the LINCS Steering Committee and Working Group. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.
Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected to be included in the application. There is no prescribed single license for software produced in this project; however, reviewers will be asked to evaluate the software sharing and dissemination plan based on its likely impact. Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan. A dissemination plan guided by the following principles is thought to promote the largest impact:
All applications, regardless of the amount of direct costs requested for any one year, should address a Data and Software Sharing Plan.
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.
Face Page (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed.
Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed.
Table of Contents (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed.
Detailed Budget for Initial Budget Period (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Data Generation activities. Travel for scientific meetings and conferences, as well as Data Generation Component-specific travel should be requested in this section.
Budget for Entire Proposed Period of Support (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Data Generation activities. Travel for scientific meetings and conferences, as well as Data Generation Component-specific travel should be requested in this section.
Biographical Sketch (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Include the biographical sketches for the Data Generation Component lead(s) as well as others involved in the Data Generation activities.
Resources (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Describe all resources available for the data generation activities.
Research Plan (Data Generation Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Specific Aims: This section should include the data generation Specific Aims.
Research Strategy: Data generation is one of the two major activities of the LINCS DSGC center. Projects should focus on high- to medium-throughput assays and a broad and scientifically justified range of cell types and perturbations. The important elements of the focus of the LINCS program are described above in the Objectives section, sub-section 'A: Data Generation'. It is important to contextualize your application and specific aims within the existing LINCS resources (and other community resource efforts) and explicitly identify the important advances in biomedical, translational, or clinical research.
Each application should include a description of any technology development that will be undertaken during the first three years of the project and explicitly delineate specific milestones that will describe intermediate evaluation steps. The application should clearly identify how such technology development will enhance one or more of overall goals and aims of the LINCS program.
LINCS is a community resource project and, as such, it is expected that detailed SOPs will be published and disseminated to the community. Careful thought should be provided in the application on how the biomedical research community's needs and priorities will be determined on a continuing basis for choices of cell types and perturbations that will be assayed.
As detailed above, the LINCS data matrix cannot feasibly be fully populated and thus experimental design is crucial; the applications should focus on aims that are likely to have a broad impact on multiple diseases or other basic biology challenges. The LINCS data matrix is expected to both lead to and be used to test hypotheses that the broader research community can utilize for further research. The application should scientifically justify that the specific aims proposed are likely to lead to the creation of such a resource for the community. Experimental design for use in such a broad community resource will be a crucial element of the specific aims and should be carefully and scientifically justified.
The applications are expected to be in a position to generate relevant data within a short period of time, certainly within the first year of the award. Relevant analytical or technical pipelines for access to cells and other necessary reagents should be in hand or readily available so that data generation metrics can be achieved. Similar considerations apply to any analytical pipelines that convert raw data to processed data (see next component for signature generation). Algorithms that are used for data processing should also, as relevant, be made publicly accessible.
Useful data and metadata standards are crucial for generating signatures that can be utilized by the community or for addressing data integration challenges. An important goal of the LINCS program is to promote a culture where a large body of annotated and shareable data and analytical tools is available online for use by the broad biomedical research community. The development and use of data and metadata standards are critical for achieving this goal. The application should focus on the identification and incorporation of such annotation as an integral part of the data generation efforts. Community engagement is essential for any such effort and applications should describe which existing community standards are most relevant for their application and how they propose to integrate their efforts with the overall standards efforts prevalent within the biomedical community.
The applicant must justify the proposed cell type choices. We anticipate that during the course of the grant, each applicant will expand the types of cells studied in collaboration with other participants in the LINCS program and with outside researchers in order to generate a more coherent resource. Thus, applicants should indicate their willingness to participate in such collaborations and should describe a plan that would enable such interactions. Applicants should set aside a reasonable (based on scientific, technical, and cost constraints) percentage of cell types to be assayed to accommodate such collaborative data generation. If applicants propose to use cells that are difficult to grow in culture in order to meet assay conditions (such as obtaining adequate cell numbers for performing a particular assay), careful attention should be paid to potential difficulties in obtaining these cells in sufficient quantities.
Single-cell profiling assays can be proposed if scientifically justified within the context of a community resource. Preliminary evidence should be provided that useful and broad signatures can be derived in a replicable manner from the assays proposed. If multiple assays, readouts, etc. are proposed in an application, the applicant should justify how these multiple assays are informative in deriving useful signatures. It is expected that applicants will propose reasonable, scientifically justified data and signature production generated by hypotheses-free approaches at a scale that would be of interest to the broader scientific community. However, applicants may choose to also propose assays that focus on the study and response of specific cell states to specific perturbations.
The applicant is encouraged to propose creative solutions for sampling the LINCS data matrix that will result in building the most valuable set of signatures that would be of broad utility to large sections of the biomedical community. The applicant must demonstrate flexibility in the selection and choice of cell types and perturbations to enable the LINCS program to collectively coordinate data generation to the maximum extent possible. The applicant should indicate willingness to participate in such coordinated data generation activities across the consortium.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide. Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.
Face Page (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed.
Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed.
Table of Contents (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed.
Detailed Budget for Initial Budget Period (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Data Analysis & Signature generation activities. Travel for scientific meetings and conferences, as well as Data Analysis & Signature Component-specific travel should be requested in this section.
Budget for Entire Proposed Period of Support (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Data Analysis & Signature generation activities. Travel for scientific meetings and conferences, as well as Data Analysis & Signature generation Component-specific travel should be requested in this section.
Biographical Sketch (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Include the biographical sketches for the Data Analysis & Signature Component lead(s) as well as others involved in the Data Analysis & Signature activities.
Resources (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: describe all resources available for the Data Analysis & Signature activities.
Research Plan (Data Analysis & Signature Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Specific Aims: This section should include the data analysis, signature building, validation, and other data integration related Specific Aims.
Research Strategy: Data analysis is the second major activity of the LINCS DSGC center. Projects should focus on specific aims that build, validate and improve signatures based on the center’s data. The important scientific objectives of the Data Analysis & Signature component of the LINCS program are described above in the Objectives section, sub-section 'B: Data Analysis & Signature Generation'. It is important to clearly and separately articulate the types of signatures and domain of applicability of the analysis, signature generation and integration activities proposed. If the application proposes to integrate the new signatures with existing LINCS (or other community resource) signatures, these should be separately identified. It is expected that the signatures and data integration activities contextualize your application and specific aims within the larger landscape of existing community resources (including efforts like the LINCS pilot, GTEx, TCGA, ENCODE, etc.).
Each application should explicitly identify: (1) the query, browsing and visualization tools that will be built for use by the typical biomedical researchers, explaining the types of analysis that will be facilitated; (2) enabling access to data, standards, and algorithms through the use of appropriate Application Programming Interfaces (APIs) for access by computational scientists; and (3) the software strategies that will be adopted to enable the future DCIC to deploy a unified graphical user interface of all LINCS resources to the community.
LINCS is a community resource project and as such it is expected that detailed analytical SOPs will be published and disseminated to the community in a timely manner. Careful thought should be provided in the application on how the biomedical research community's needs and priorities will be determined on a continuing basis for the types and queries, tools and visualizations that will be built and deployed.
The applicants are expected to be in a position to build, and enable deployment of the tools within a short period of time, certainly within the first year of the award. Computational validation of the query, browsing and other analytical tools and signatures are an essential part of the LINCS resources and, as such, appropriate gold standard data sets should be identified or built and published to the community. The applicants should describe a viable plan for adopting and deploying improved tools contributed by the community.
A clear strategy should be identified for enabling and deploying the results of compute-intensive queries or other processing algorithms within the context of a community resource. An appropriate balance is likely needed for a community resource in enabling compute-intensive algorithms and a clear principle of how this will be achieved should be articulated. It is the applicant's responsibility to provide access to all proposed analytical resources to the DCIC for deployment. Additionally, it would be possible in the future to collaborate with the DCIC to build additional computational access for typical biomedical researchers.
The biological relevance of the proposed signatures can be demonstrated via prior publications or other preliminary data. The refinement or improvement of the signatures will be a continuing activity of the work proposed within this Component, while demonstrating the broad applicability and utility of the signatures and data generated within the DSGC will primarily fall into the Community Interaction and Outreach Component of the application.
Since signatures may be based on statistical approaches or may represent more complicated entities (such as cell-type specific signaling pathways or predictive cardiotoxicity markers), the applicants are expected to catalog or create a table of the types of signatures being proposed. Additionally, applicants are encouraged to consider signatures that may build upon other available community datasets and resources (e.g., from the LINCS pilot or others).
Applicants that propose more than one assay type must also propose analysis and community access tools (including visualization, browsing, and querying capabilities) for each of the data types. Applicants with multiple data types should also propose relevant data integration activities to support integrative queries from users.
Each DSGC applicant should carefully address how s/he proposes to enable a future DCIC to provide access to all of their LINCS resources. For example, the DSGC applicant should also propose a number of simple visualization elements that can be used by the DCIC to develop and populate a comprehensive tool that would integrate appropriate elements from multiple DSGCs. The DCIC would also establish portal-like features that would let users launch visualization, browsing, or query tools to support exploration of individual data types in detail. While the DCIC may facilitate access to such tools, it is expected that each DSGC will develop and make them available.
The applicants are expected to propose creative solutions for storing the data and signatures they generate and making them, along with any associated software code, tools, and algorithms, available to the research community. Applicants should provide a data, signature, and tool management plan that is scalable, accessible, and sustainable.
Applicants should provide details on both data and tool annotation and accessibility that specifically identify which community standards and best practices they have chosen.
Applicants are expected to identify the metadata standards they will adopt and provide a range of use-cases they expect to support with the metadata. The applicants should identify and scientifically justify their approach to metadata annotation and curation for their data types (at the level of the basic elements of the datasets, including cell lines, small molecules, etc., as well as at the experimental and analytical levels) and should explicitly identify community resources they plan to leverage (ontologies, controlled vocabularies, and relevant Minimum-Information standards like MIAME). The applicants are encouraged to examine the standards being used in the LINCS pilot effort and adapt or enhance these resources as needed. The applicant should indicate a willingness to work within the consortium to ensure compatible data, signature, and tool annotation.
It is not expected that each DSGC would budget for resources for building their own deployable user interface to expose their own download and query/visualization tools to the community. The applicants should clearly elaborate database and software engineering principles that will be followed for the different tasks. Such tasks could include building suitable application programming interfaces, or data exchange standards that are generalizable, or support multiple assay types joins using e.g., JSON, or define and support key visualization elements , or other widgets. It is expected that the DSGC will make available to the DCIC suitable capabilities that would enable the DCIC to provide effective linked and faceted visualizations of data across multiple DSGC resources.
The applicants should demonstrate the capability of building software tools that can be adapted and deployed by other groups (e.g., the DCIC). This effort could include (a) incorporating modern approaches that may include REST APIs, developed for or outside a cloud environment, or (b) building tools that include sufficient levels of abstraction, or (c) agile software development, or (d) other features to enable ease of deployment and integration of distributed and fundamentally disparate data types stored in different databases.
For visualizations, applicants are encouraged to propose adopting existing extensible software frameworks that would make it easier for the DCIC to leverage or deploy the visualizations created by the DSGC. DSGC applicants should consider approaches like providing support for visual representations of their databases, lower-dimensional representation , etc. It is expected that such approaches will enable both the DCIC and the community to understand the content of the database (and LINCS matrix) so that they can generate sharper, more relevant queries. Applicants should be prepared to provide details of their database schema and assist the LINCS DCIC in replicating the schema and algorithms at a different location. The applicant should clearly identify the infrastructure needed to run analysis algorithms and software to support queries, analysis tools, and visualizations of their data and signatures and that can reasonably be expected to be deployed by the future DCIC.
The applicant should carefully propose a practical and viable plan to work in close cooperation with the DCIC and other DSGCs in developing a useful and deployable LINCS resource for the entire biomedical research community that will provide easy and useful access to both computational and bench scientists.
Applicants should make available appropriate documentation and tutorials to ensure that researchers can access and use the data, tools, SOPs, and signatures generated by the DSGC.
Applicants should provide access to the community to all data and analytical tools needed to support the results, tables, and figures (as appropriate) in any publications that come from LINCS efforts. Creative solutions for such access from published figures back to data and analytics should be proposed. Finally, applicants must identify suitable public repositories (if available) for their data types, and propose a viable plan to deposit data from their LINCS database into such repositories (e.g., NCBI, EBI, or others) on at least a semi-annual basis.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide. Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.
Face Page (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed.
Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed.
Table of Contents (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed.
Detailed Budget for Initial Budget Period (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Community Interactions and Outreach activities. Travel for scientific meetings and conferences, as well as Community Interactions and Outreach-specific travel should be requested in this section.
Budget for Entire Proposed Period of Support (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Community Interactions and Outreach activities. Travel for scientific meetings and conferences, as well as Community Interactions and Outreach Component -specific travel should be requested in this section.
Biographical Sketch (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Include the biographical sketches for the Community Interactions and Outreach Component lead(s) as well as others involved in the Community Interactions and Outreach Component activities.
Resources (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Describe all resources available for the data generation activities.
Research Plan (Community Interactions and Outreach Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Specific Aims: This section should include specific aims related to activities in the Objectives section C, specifically, sub-sections C3 and C4. Please note that activities corresponding to sub-sections C1 and C2 have already been addressed above in the Data Analysis & Signature Generation Component.
Research Strategy: Community engagement is an important tool for each DSGC to enable dissemination of the proposed resources in the application. As such, it is expected that the applicant will identify sources of any non-LINCS data of the same type proposed in the Data Generation Component of the application, with the aim of facilitating its access from within the LINCS resource. The primary responsibility of incorporating such non-LINCS data for suitable data integration tasks will be the future DCIC s. However, it is expected that the DSGC will act as an active resource for the entire LINCS program in enabling access to suitable, existing, community data and resources. Plans for enabling this role should be clearly articulated along with the identification and application of suitable analytical and computational methods to build LINCS-compatible signatures. It is expected that each applicant will provide sufficient resources to enable this crucial component. Research on the suitability of incorporating such external signatures into the LINCS resource either for signature-based queries or other data integration tasks is the responsibility of the DSGC and should be part of the Data Analysis & Signature Generation Component above.
Working with suitable collaborating partners from outside the LINCS program is crucial for achieving NIH’s long-terms goals for the LINCS program. The major aim of these Community Interaction Projects is to demonstrate the value of the proposed techniques and data in scientific domains that are not the primary expertise of the PI(s) of the DSGC. Therefore, for the first year of the application, applicants are encouraged to explicitly identify up to two small Community Interaction Projects that would enable researchers in such other areas to access LINCS resources in a facile and specifically relevant manner. Beyond the first year, the application should present suitable plans and approaches that would continue the identification and evaluation of non-LINCS researchers on an ongoing basis. However, it is not expected that the application contain specific Community Interaction Projects beyond the first year of the proposed project.
As mentioned above, applicants to the current FOA will be responsible for providing access to bench scientists for all aspects of the analysis, visualization, query, and integration of the data generated by their DSGC, and for providing their resources to the future DCIC for further deployment.
Applicants are encouraged to propose plans for suitable tutorials, webinars, workshops or challenges that focus on the use of their uniquely generated data and analytical resources to stimulate use of their resources.
Each applicant is expected to identify high quality, relevant non-LINCS data sets that might be incorporated into LINCS. Applicants should provide plans to support this role and should also identify specific data and resources and how LINCS-compatible signatures might be generated. A tabular presentation of the identified resources should be offered. Applicants may propose to leverage major data repositories and domain-specific resources, as best suits their scientific area. Consideration should be given to addressing any special challenges for assessing quality metrics, availability of suitable metadata, or robust algorithms for signature generation using non-LINCS data sources.
Community Interaction Projects that are proposed may be actual collaborations with outside scientists involving specific data generation; to ensure that each DSGC engages in a sufficient number of such collaborations, they would typically be relatively small and last one year. The funds to support the collaborations may be requested as part of the DSGC budget or may be provided by the collaborator. However, applicants may propose other innovative solutions to foster community interaction in quest of dissemination of the LINCS approach. In total, community interaction projects are expected to be about 10% of the entire DSGC effort each year.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide. Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.
All instructions in the PHS398 Application Guide must be followed, with the following additional instructions, as noted.
Face Page (Administration Component)
All instructions in the PHS 398 Application Guide must be followed.
Description, Project/Performance Sites, Senior/Key Personnel, Other Significant Contributors, Human Embryonic Stem Cells (Administration Component)
All instructions in the PHS 398 Application Guide must be followed.
Table of Contents (Administration Component)
All instructions in the PHS 398 Application Guide must be followed.
Detailed Budget for Initial Budget Period (Administration Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Administration activities. Travel for LINCS-wide community workshops, as well as annual LINCS Steering Committee meetings should be requested in this section.
Budget for Entire Proposed Period of Support (Administration Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Provide a budget that includes funds for Administration activities. Travel for LINCS-wide community workshops, as well as annual LINCS Steering Committee meetings should be requested in this section.
Center Director’s effort: The Center Director (PD/PI) should be the overall lead of the Administration component. The scientific and managerial complexity of a DSGC will require a substantial amount of the PD/PI's effort to be successful. The Center Director may participate in multiple center awards under this FOA, but cannot serve as PD/PI on more than one active DSGC award. The PD/PI of a Center grant must commit a minimum effort of 3 months per year to the Center distributed across all components; if there are multiple PDs/PIs, then one must commit at least 3 months per year and the others must commit at least 2.4 months per year to the Center distributed across all components.
Biographical Sketch (Administration Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Include the biographical sketches for the Administration lead(s) as well as others involved in the Administration activities.
Resources (Administration Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions: Describe all resources available for Administration activities.
Research Plan (Administration Component)
All instructions in the PHS 398 Application Guide must be followed, with the following additional instructions:
Specific Aims: This section should include the Administration-related Specific Aims. See sub-section D of the Objectives above for more details.
Research Strategy: The Research Strategy of the Administration component should include the following information:
Administrative Plan: The application should describe the management and integration of activities in the Center. Applicants should specify appropriate administrative/business management staff, as well as the oversight mechanisms that will be used by the Center Director (PD/PI), any Center Co-Directors, and any other relevant key personnel. If multiple geographic sites are involved in the proposed Center, the Administrative Plan should describe the leadership and communication plans to manage the multiple sites. The applicant should describe the proposed Center structure and the application may include an organizational chart.
Assessment of Progress: The Administrative Plan should describe a set of milestones or defined objectives that the PD/PI and NIH staff can use for annual assessments of whether the proposed research and other activities of the Center are progressing appropriately toward the goals of the Center. NIH recognizes that some basic research accomplishments may not be easily quantifiable; thus, the PD/PI should propose appropriate criteria to measure the progress of the research. The proposed milestones or objectives for the out-years may be less detailed than those for the first year of the project. Since the award uses the Cooperative Agreement mechanism, a set of Center milestones or objectives will be negotiated with program staff prior to the award. Similarly, a set of milestones or objectives for the LINCS Consortium will be negotiated after the award. Progress toward the milestones or objectives should be reported annually, and the milestones will be reconsidered, and renegotiated if necessary, as part of the annual non-competing continuation application (Type 5) process. The list of Center milestones or objectives should be limited to two pages.
Evaluation, including Mid-Course Review: The Administrative Plan should include a plan for evaluating the quality and utility of the Center products and training. Criteria of evaluation for Center products may include adequacy, trustworthiness, authenticity, integrity, availability, documentation, and transparency. Specific examples of evaluative information could include tracking the number of users, background/training of the users, requests for services, successful use of the Center products, publications citing uses, number of students, use of training materials, the ability to extend the utility of tools through collaborations with other Centers, etc. The research community being served will have expectations that could be documented through mechanisms such as user feedback, letters of support, etc. There should be evaluative measures for both short-term and long-term outcomes. Applicants are encouraged to identify relevant milestones for the mid-course review as described in the section 'Objectives of this Research Project', specifically sub-section E3. Quantifiable measures of intermediate results and success are important and should be built in as:
Infrastructure: LINCS research requires appropriate computer, data storage, and networking infrastructure resources. The application should describe the infrastructure resources that are available, to be obtained, or will be developed during the award, and justify how these resources will be used to support the research at the host institution as well as the biomedical research community.
Transition Plan: The intent of NIH Common Fund programs is to provide a strategic and nimble approach to address key roadblocks in biomedical research that impede basic scientific discovery and its translation into improved human health.
The LINCS Program aims to catalyze a change in academic and public-sector biomedical research by making the LINCS resource and approaches available to the community. The NIH Common Fund provides funding to support an incubator space for this program to develop and mature.
However, planning of Common Fund projects includes the eventual transition of support from the Common Fund to alternative sources, which may include individual NIH Institutes and Centers or other sources of funding, as the transformative effects of the Common Fund project are realized. For the LINCS program, active work towards a transition will begin in the fourth year of the Program with the Community Interaction and Outreach component playing an important role in building towards such a transition. Applicants are expected to provide a transition plan in the application describing approaches that would result in long-term support for the LINCS resources beyond the 6-year funding of this FOA. These plans will likely be modified and improved during the period of award in conjunction with the NIH LINCS Working Group (see Section VI. Award Administration below).
For purposes of the present FOA, applicants should provide a budget request for all six-years. However, applicants should realize that the award of the last three-year transition phase following the NIH Mid-Course review will be based on program priorities, availability of funds, and successful completion of negotiated scientific milestones as determined by NIH staff in the context of the NIH Midcourse review. Applicants are advised to refine their transition plans during the first three years of the award to accommodate other potential mechanisms of support, such as fee for service and/or private funding.
Awardees will be expected to work with NIH to develop tracking and reporting on their data, signature, and tool generation and the usage of these by the research community.
Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans (Data Sharing Plan, Sharing Model Organisms, and Genome Wide Association Studies (GWAS)) as provided in the PHS 398 Application Guide. Applicants are instructed to place the Resource Sharing Plan only in the Overall Component.
Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix (please note all format requirements) as described in the PHS 398 Application Guide.
Part I. Overview Information contains information about Key Dates.
Information on the process of receipt and determining if
your application is considered on-time is described in detail in the PHS 398
Application Guide.
Applicants may track the status of the application in the eRA Commons, NIH’s electronic system for grants
administration.
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 received on or before the due dates in Part I. Overview Information. If an application is received after that date, it will not be reviewed.
Upon receipt, applications will be evaluated for completeness by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete and/or nonresponsive will not be reviewed.
An Applicant Information Webinar will be held on Friday, September 6, 2013, from 3 4:30 pm EDT, to provide information about the FOA to prospective applicants. NIH staff will provide an overview of the FOA and answer questions. The webinar is open to all prospective applicants. Participation in the teleconference is not a prerequisite for applying, and is not required for a successful application. Information about how to participate in the webinar will be posted at http://commonfund.nih.gov/lincs/. Potential applicants are encouraged to submit their questions or comments to [email protected] prior to the meeting. Afterwards, the webinar slides and a summary of the questions and answers will be posted on the same site. NIH will also post a list of Frequently Asked Questions (FAQs) and answers; this information may be updated without additional notice.
The requests by NIH intramural scientists will be limited to the incremental costs required for participation. As such, these requests will not include any salary and related fringe benefits for career, career conditional or other Federal employees (civilian or uniformed service) with permanent appointments under existing position ceilings or any costs related to administrative or facilities support (equivalent to Facilities and Administrative or F&A costs). These costs may include salary for staff to be specifically hired under a temporary appointment for the project, consultant costs, equipment, supplies, travel, and other items typically listed under Other Expenses. Applicants should indicate the number of person-months devoted to the project, even if no funds are requested for salary and fringe benefits.
If selected, appropriate funding will be provided by the NIH Intramural Program. NIH intramural scientists will participate in this program as PDs/PIs in accord with the Terms and Conditions provided in this FOA. Intellectual property will be managed in accord with established policy of the NIH in compliance with Executive Order 10096, as amended, 45 CFR Part 7; patent rights for inventions developed in NIH facilities are NIH property unless NIH waives its rights.
Should an extramural application include the collaboration with an intramural scientist, no funds for the support of the intramural scientist may be requested in the application. The intramural scientist may submit a separate request for intramural funding as described above.
Applicants are required to follow the instructions for post-submission materials, as described in
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 individual criterion scores for the Overall Center, but not for each component. They will provide written narratives for all the components of the application. The impact score of the Overall Center is the impact score of the entire application.
The Overall Center impact score will emphasize a) the overall effectiveness and innovation of the approaches, methods, software, tools, and related resources in generating perturbagen-response data for the LINCS program; b) the scientific merit of the proposed data and signature generation, analysis and community interactions and outreach activities, including the potential generalizability of the results to other areas of biomedical research; c) the qualifications of the Center Director and other staff; d) the quality of the plans for management and oversight of the Center; e) the adequacy of plans for the release of data, methods, software, tools, and related dissemination activities; f) the synergy among the components; g) the proposed contribution to the LINCS consortium activities; and h) the overall impact of the Center. The overall impact score for the DSGC application may be higher or lower than the average of the individual components based on assessment of whether the whole is greater than the sum of its components.
Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the centert 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 centerproposed).
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 centert that by its nature is not innovative may be essential to advance a field.
Significance
Does the center address an important problem or a critical barrier to progress in the field? If the aims of the centert 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? Is the proposed project likely to result in a significant public resource? Are the perturbagens/cell lines/readouts proposed biologically significant? Is the proposed project likely to facilitate progress on a wide range of biological or medical problems? How well does the application address the Research Objectives of the FOA?
Investigator(s)
Are the PD(s)/PI(s), collaborators, and other researchers well suited to the DSGC Center? 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?
Innovation
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?
Approach
Are the overall strategy, methodology, and analyses
well-reasoned and appropriate to accomplish the specific aims of thecenter? 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?
If the centerinvolves clinical research, are the plans for 1) protection of
human subjects from research risks, and 2) inclusion of minorities and members
of both sexes/genders, as well as the inclusion of children, justified in terms
of the scientific goals and research strategy proposed?
Will the approach result in a resource that can be integrated with other data from the community (e.g., genetic, expression, proteomic, etc. data; small molecules; pharmaceutical research) and across the LINCS program? Are the three major functions (Data Generation, Data Analysis & Signature Generation, and Community Interactions and Outreach) properly coordinated? Does the Data Generation section describe and adequately justify appropriate goals, timelines, and milestones? Are plans for Laboratory Technology Development in the first three years well justified and coordinated with the goals of the application? Are the proposed signatures scientifically justified and potentially useful and generalizable? Are the data and software management and sharing plans adequate to make these resources available within the LINCS consortium and to the larger research community, including both bench biomedical and computational researchers? Are the proposed use of community standards for data and metadata adequate and relevant? Is the Program Administration plan appropriate to the complexity of the proposed effort? Are the plans for participation in the LINCS Consortium adequate, and is there a viable plan for coordinating data generation across the LINCS consortium? How effectively will the chosen perturbagen/cell line/assays provide the most useful set of information of cellular responses? Are the choices of the perturbagens, cell lines or tissues, proposed readouts and related experimental protocols adequately justified and likely to lead to the creation of a valuable public resource that can be used by the whole biomedical research community? Are the proposed plans for sharing the data, the experimental protocols, models and software release plans scientifically meritorious and beneficial to the overall goals of the LINCS program?
Environment
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?
Integration of the DSGC Center
Will the whole Center be greater than the sum of its individual components? Do coordination and integration among the proposed components reflect a cohesive research program?
As applicable for the Center 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 Generation:
Review Criteria for Data Analysis & Signature:
Review Criteria for Center Administration:
Protections for Human Subjects
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.
Inclusion of Women, Minorities, and Children
When the proposed project involves clinical research, the committee will evaluate the proposed plans for inclusion of minorities and members of both genders, as well as the inclusion of children. 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 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.
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) Genome Wide Association Studies (GWAS).
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 the Center for Scientific Review, 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 response to this FOA.
Applications will be assigned to the appropriate NIH Institute or Center and 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. 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 the DUNS, SAM
Registration, and Transparency Act requirements as noted on the Award
Conditions and Information for NIH Grants 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.
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 Parts 74 and 92 (Part 92 is applicable
when State and local Governments are eligible to apply), and other HHS, PHS,
and NIH grant administration policies.
The administrative and funding instrument used for this program will be the
cooperative agreement, an "assistance" mechanism (rather than an
"acquisition" mechanism), in which substantial NIH programmatic
involvement with the awardees is anticipated during the performance of the
activities. Under the cooperative agreement, the NIH purpose is to support and
stimulate the recipients' activities by involvement in and otherwise working
jointly with the award recipients in a partnership role; it is not to assume
direction, prime responsibility, or a dominant role in the activities.
Consistent with this concept, the dominant role and prime responsibility
resides with the awardees for the project as a whole, although specific tasks
and activities may be shared among the awardees and the NIH as defined below.
The PD(s)/PI(s) will have the primary responsibility for:
The Program Director/Principal Investigator will have the primary responsibility for: defining the details for the projects within the guidelines of this FOA, and for performing all scientific activities. The PD/PI will agree to accept the close coordination, cooperation, and participation of the NIH staff (LINCS Program Officials, Project Scientists, the Working Group Leader, and the LINCS Working Group) in those aspects of scientific and technical management of the project as described below. Specifically, the PD/PI of this LINCS center will:
NIH staff have substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:
The LINCS Project Scientists will have the following substantial involvement:
LINCS Working Group Responsibilities. The LINCS Working Group will serve as the trans-NIH body overseeing and coordinating the activities of all LINCS components. Working Group membership will include one or more representative(s) from each of the NIH Institutes and Centers (IC) participating in the LINCS program. Program Officials and Project Scientists can be members of the LINCS Working Group. Each participating NIH IC will have a single vote on the Working Group, no matter how many members from the NIH IC are involved. The Working Group will receive recommendations from the LINCS Steering Committee. The LINCS Working Group will have the following involvement:
Areas of Joint Responsibility include:
LINCS Steering Committee Functions. The LINCS Steering Committee is the operational group responsible for coordination of the activities of all components of the LINCS. The LINCS Steering Committee will identify scientific and policy issues that need to be addressed by all components of the LINCS program, develop recommendations to the Working Group for addressing such issues, coordinate the primary recommendations for choice of experimental protocol, and coordinate the dissemination of data, assay protocols, and other materials with the wider scientific community.
The LINCS Steering Committee membership will include the PD/PI of each of the components of the LINCS program and the DCIC from the future LINCS-related FOA, and the Project Scientists. The PD/PI of each center (or designee) will have one vote on the LINCS Steering Committee. The Project Scientists may vote, but the total votes will count as a maximum of one-third of the total LINCS Steering Committee votes. Membership on the Steering Committee becomes effective upon issuance of the Notice of Award. The Steering Committee may add additional members if technology development, data generation, coordination, standardization or integration activities will benefit from such an expansion. Other NIH staff may attend the Steering Committee meetings, if their expertise is required for specific discussions. The LINCS Steering Committee may establish additional subcommittees or workgroups for specific tasks. No NIH staff member may chair any committee or subcommittee of the Steering Committee. The LINCS Steering Committee will:
External Scientific Panel (ESP): The ESP will be responsible for reviewing and evaluating the progress of the LINCS program in meeting their individual and collective milestones and goals, and making recommendations about the progress and directions of the LINCS program and individual components to the LINCS Working Group. The ESP will be composed of 4-6 senior non-federal scientists who are not directly involved in the activities of the LINCS program. The LINCS Working Group will appoint members to the ESP. The LINCS Working Group will select one member as chair. The LINCS Project Scientists and LINCS Working Group members may attend the External Scientific Panel meetings as non-voting participants. The ESP will have the following involvement:
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 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 Non-Competing Continuation Grant Progress Report (PHS 2590 or RPPR) annually and financial statements as required in the NIH Grants Policy Statement.
A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.
The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.
We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.
eRA Commons Help Desk (Questions regarding eRA Commons
registration, submitting and tracking an application, documenting system
problems that threaten submission by the due date, post submission issues)
Telephone: 301-402-7469 or 866-504-9552 (Toll Free)
Web ticketing system: https://public.era.nih.gov/commonshelp
TTY: 301-451-5939
Email: [email protected]
GrantsInfo (Questions regarding application instructions and
process, finding NIH grant resources)
Telephone: 301-710-0267
TTY: 301-451-5936
Email: [email protected]
Ajay Pillai, Ph.D.
National Human Genome Research Institute (NHGRI)
Telephone: 301-594-7108
Email: [email protected]
Jennie Larkin, Ph.D.
National Heart, Lung, and
Blood Institute (NHLBI)
Telephone: 301-435-0513
Email: [email protected]
David Balasundaram, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-435-1022
Email: [email protected]
Cheryl Chick
National Human Genome Research Institute (NHGRI)
Telephone: 301-435-7858
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 Parts 74 and 92.
Weekly TOC for this Announcement
NIH Funding Opportunities and Notices
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