It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, except where instructed to do otherwise (in this FOA or in a Notice from the NIH Guide for Grants and Contracts). Conformance to all requirements (both in the Application Guide and the FOA) is required and strictly enforced. Applicants must read and follow all application instructions in the Application Guide as well as any program-specific instructions noted in Section IV. When the program-specific instructions deviate from those in the Application Guide, follow the program-specific instructions. Applications that do not comply with these instructions may be delayed or not accepted for review.

Part 1. Overview Information
Part 2. Full Text of the Announcement

Section I. Funding Opportunity Description
Section II. Award Information
Section III. Eligibility Information
Section IV. Application and Submission Information
Section V. Application Review Information
Section VI. Award Administration Information
Section VII. Agency Contacts
Section VIII. Other Information

Introduction

This FOA is a part of the Implementation Phase of the NIH Common Fund program, Illuminating the Druggable Genome (IDG). 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 human genome has revealed a great deal about the human proteome, though significant portions remain understudied. Only a subset of expressed proteins demonstrates the requisite properties to serve as targets for the development of therapeutics. Many bona fide drug targets likely remain to be discovered in the Druggable Genome (DG), which has been defined as the subset of the ~30,000 genes in the human genome that express proteins potentially able to bind drug-like molecules. The term "drug-like" refers to the physical, biochemical, and pharmacological attributes of small molecule compounds that are generally recognized to be required for efficacious clinical drugs in humans. While the number of proteins in the DG is upwards of 6,000, the existing clinical pharmacopeia is represented by only a few hundred targets, leaving a huge swath of biology that remains unexploited.

The discovery of a disease association or the development of a useful tool reagent can accelerate research into a previous understudied protein, such as was the case for BRAF. Thus, while many interesting and critical biological processes and potential therapeutic avenues remain unexplored because an initial, catalyzing event has not yet occurred, the IDG Program will address this bottleneck by systematically querying these understudied proteins to find phenotypic associations and develop useful research tools.

While at the informatics level, genome- and proteome-wide tools can collate information and query all proteins, technical feasibility necessitates a narrower focus of experimental efforts into protein families for which there are definable understudied members along with existing technologies that can be readily adapted at the scale necessary for wholesale elucidation of their function and generation of tools. During the Pilot Phase of the IDG, it was determined that the experimental focus of the IDG will be on the understudied members in the families of non-olfactory GPCRs, ion channels, and protein kinases, as these families contain adequate numbers of understudied members and are well-established druggable families with high potential to impact human health once disease associations are made. While there are numerous valid approaches to defining understudied proteins, for the purpose of the IDG Program the NIH determined that use of bibliometric measures, e.g., the Jensen PubMed Score (JS; a fractional count of publications correcting for a number of sources of false positives) coupled with a lack of R01 funding was the most useful in terms of identifying a common, working definition of understudied proteins. At the time of preparation of these FOAs, 395 of the 1325 proteins in the GPCR, ion channel, and protein kinase families met these criteria; 143 GPCRs, 118 ion channels, and 134 kinases had a JS < 50, no R01s, and a PubTator score < 150.

The HUGO Gene Nomenclature Committee symbols for the protein targets that will be the initial focus of the IDG Program can be found here:

Kinases

PRKAG1, PRKAB1, ADCK2, ADCK5, ALPK3, ADCK4, ALPK2, BCKDK, CAMKV, CDKL3, CDKL4, CDKL1, CDKL2, CDK15, CDK17, CDK11B, CDK14, CDK18, CLK4, CDK10, CLK3, CSNK2A2, DGKH, DYRK3, DYRK1B, DYRK4, EEF2K, DYRK2, ERN2, FASTK, GK2, HIPK4, ITPKA, CSNK1G3, CSNK1G2, PRKACG, CSNK1G1, ITPK1, PSKH2, CAMK1D, TK2, PRKACB, PNCK, CAMK1G, CAMKK1, PSKH1, PHKA1, RPS6KC1, PRKCQ, LMTK3, MARK4, MAST3, LRRK1, MAP3K14, LTK, MAP3K10, MAST4, MAST2, MAPK15, MAPK4, MKNK2, CDC42BPG, CDC42BPB, NEK11, NEK5, NEK10, NIM1K, NEK4, NEK6, NRK, NEK7, SCYL1, NRBP2, PIK3C2G, PAK7, PANK3, PIK3C2B, PAK3, PAK6, SCYL3, PDIK1L, PIP4K2C, PIP5K1A, PLK5, PHKG1, PHKG2, PI4KA, PIP5K1B, PKMYT1, PKN3, PRPF4B, TP53RK, PRKRA, PRKY, PXK, RIOK1, RIOK3, RPS6KL1, SBK2, SCYL2, SBK3, SGK494, POMK, SGK223, SRPK3, STK32C, STK33, STK32B, STK40, STK17A, STK36, STK32A, STK38L, STKLD1, STK3, STK31, TESK2, TESK1, TBCK, TLK1, TPK1, TLK2, TSSK6, TSSK1B, TTBK2, TSSK4, TTBK1, TSSK3, UCK1, ULK4, UCK2, WNK2, VRK2, WEE2

Ion channels

HTR3B, HTR3E, HTR3D, CHRNB2, HTR3C, CHRND, CHRNB1, CHRNA10, CHRNA2, CHRNA9, CHRNG, ASIC4, ASIC5, BEST4, CACNA2D1, CACNA2D3, CACNA2D4, CACNB1, CACNB2, CACNB3, CACNA2D2, CACNG6, CACNA1F, CACNB4, CACNG1, CACNG5, CACNG3, CACNG7, CACNG4, CACNG8, CLCNKA, CLIC6, CLIC2, CLCA4, CLCC1, CLCA3P, CNGA4, CLCN6, CLIC5, CLCA2, CLIC3, CATSPER4, CATSPER2, FAM26F, FAM26D, FAM26E, FXYD3, FXYD7, FXYD6P3, GABRA6, GABRG3, GABRR3, GABRB1, GABRG1, GABRP, GABRA5, GABRR1, GPR89A, GLRA3, GLRA4, GLRB, GPR89A, GRID1, GRIK3, HCN3, KCND1, KCNK4, KCNK7, KCNS1, KCNS2, KCNIP1, KCNJ15, KCNMB4, KCNK16, ITPR2, KCNH6, KCNH7, KCNH8, KCNK12, KCNMB3, KCNA6, KCNG2, KCNN1, KCNAB2, KCNIP4, KCNC4, KCNG3, KCNH4, KCNS3, KCNAB3, KCNG4, KCNA7, KCNT1, KCNJ14, KCNJ18, KCNV1, LRRC52, LRRC55, LRRC38, PANX3, PANX2, PLLP, PKD1L2, PKD2L2, PKD1L3, SLC26A1, SCN3B, SCN7A, SCNN1D, SCN2B, SCNN1B, TMC5, TMC7, TMEM38B, TMC3, TMC4, TTYH2, TTYH1

GPCRs

HTR1E, HTR5A, ADGRD1, ADGRE2, ADGRF5, ADGRG4, ADGRG7, ADGRB2, ADGRF2, ADGRF4, CHRM5, ADGRF1, ADGRG3, ADGRG5, ADGRD2, ADGRE1, ADGRE3, ADGRF3, ADGRG2, ADGRB3, ADGRA1, ADGRE4P, ADGRL3, CELSR2, GPR137, FZD10, GPR32P1, GALR3, GPR139, GPR149, GPR171, GPR174, GPR142, GPR151, GPR156, GPRC5D, GPR153, GPR33, GPR25, GPR45, GPR75, GPR88, GNRHR2, GPR150, GPR18, GPR62, GPR82, GPR87, GPR101, GPR173, GPRC5C, GPR32, GPR63, GPRC5B, GPR12, GPR135, GPR141, GPR146, GPR152, GPR157, GPR160, GPR42, GPR52, GPR143, GPR162, GPR26, GPR21, GPR61, GPR20, GPR27, GPR31, GPR34, GPR39, GPR4, GPR6, GPR78, GPR85, GPR19, GPR22, HCAR1, HCAR3, MAS1L, LPAR6, MRGPRX4, MRGPRG, MRGPRX2, MTNR1A, MRGPRE, MRGPRX3, NPBWR1, NPBWR2, NPY6R, NPY2R, NPY5R, OPN1MW2, OXGR1, P2RY10, OXER1, RRH, P2RY11, PROKR1, QRFPR, GPRC5A, RXFP3, RXFP4, S1PR4, SSTR4, SUCNR1, TAS2R31, TAS2R14, TAAR3, TAS2R10, TAS2R41, TAS2R43, TAS2R50, TAAR2, TAAR8, TAS2R19, TAS2R7, TAS2R9, TAS2R13, TAS2R20, TAS2R40, TAS2R60, TAS2R3, TAS2R4, TAS2R5, TAS2R16, TAS2R8, TAAR9, TAS2R39, TAS2R1, TAS2R30, TAS2R42, TAS2R46, TPRA1, AVPR1B, VN1R17P, VN1R3, VN1R5, VN1R1, VN1R4, VN1R2

It is expected that the priorities among the targets within these three families will change over the period of the project. The IDG Consortium is expected to transform research by revealing a number of new activities and potential drug targets amongst these understudied proteins. Moreover, it is anticipated that the IDG Consortium will enhance our understanding of on- and off-target effects by establishing functional relationships among understudied members of the commonly targeted gene families.

Thus, the overall long-term goals of the IDG Program are two-fold:

• To advance research through the development, broad dissemination, and use of community scientific resources to study human proteins for which publicly available information or active research is lacking in order to catalyze the discovery of truly novel biology, with a particular focus on understudied members of the protein kinase, ion channel, and non-olfactory GPCR families.
• To demonstrate the feasibility and benefits of illuminating the roles of understudied proteins, permitting the expansion of such approaches to a broader array of protein families beyond the three families of proteins in the IDG Program.

To accomplish these goals the IDG will be composed of awardees from at least the three initiatives desribed below. These awardees, in conjunction with future IDG initiative awardees, will form the nucleus of the IDG Consortium that will pursue the overall goals of the program. Additional non-IDG-funded members could be included in the IDG Consortium in the future.

• The Knowledge Management Center (KMC; RFA-RM-16-024) will aggregate knowledge from a protein-centric viewpoint across the entire human proteome, with an emphasis on the understudied non-olfactory GPCRs, protein kinases, and ion channels that will be the focus of the experimental initiative. The KMC will also develop a knowledge portal (the IDG Portal ) that will include the aggregated data and metadata, a query interface, and deployed informatics tools along with community access to resources developed by the IDG Consortium (see below for further specifics). The main goal of the IDG Portal is to provide access to aggregated data and IDG resources for the broad scientific community.
• Data and Resource Generation Centers (DRGCs; RFA-RM-16-026) will generate and validate new knowledge and/or tools relevant to the understudied members of the protein kinase, ion channel, and non-olfactory GPCR families with the intent of broadly and rapidly disseminating knowledge and tools to the research community. As one of the essential goals of this program, NIH intends that tools and reagents generated by the IDG Consortium will be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be used as widely as possible, enabling further investigation of understudied proteins by the larger scientific community.
• To assist in the dissemination of data and tools and the overall coordination of the IDG Consortium, a Resource Dissemination and Outreach Center (RDOC; RFA-RM-16-025) will also be established. The IDG RDOC will work with all IDG Consortium investigators to collect, curate, and disseminate information regarding critical tools and reagents being developed by the IDG Consortium through the IDG Portal.

Contingent on availability of funds, the NIH plans a future funding opportunity for a set of Cutting Edge Informatics Tools (CEITs) that will augment the capability of the KMC as well as the broader IDG Consortium by deploying tools to enhance the community’s ability to process, analyze, and visualize data around the understudied proteins. Awardees are expected to work together across initiatives to accomplish the overall goals of the IDG and to disseminate resources to the broad scientific community.

The IDG Program began as a three-year pilot. One component of this pilot tested the feasibility and utility of establishing a Knowledge Management Center (KMC) to make information available so that any biomedical researcher could easily assess a broad range of information about a protein target and identify gaps in knowledge within a gene family. The tool that was developed during the pilot phase can be found here: https://pharos.nih.gov/idg/index. It is important to emphasize that this tool is a pilot effort and should not be assumed to constrain the contours of the IDG Portal developed in response to this FOA. The information currently available in Pharos is completely open (the data, database schema, the pipelines, and other software) and will be available to the community and specifically to the awardee for further development, if needed.

Utility of the KMC to the broader community comes from consolidating and abstracting all relevant information in one place, human curation of relevant subsets, and the availability of an integrated analytical and visualization environment that enables researchers in the community to identify lack of or weak evidence supporting the biological function or disease relevance of a protein target.

The overarching goal of this Funding Opportunity Announcement (FOA) and its companion announcements is to generate a research consortium to facilitate the unveiling of the functions of selected understudied proteins in the Druggable Genome using experimental and informatics approaches. The IDG Consortium will be a part of the Implementation Phase of the Common Fund program, Illuminating the Druggable Genome (IDG; https://commonfund.nih.gov/idg/index). This IDG Consortium will be composed of multiple Data and Resource Generation Centers (DRGCs; RFA-RM-16-026), a Knowledge Management Center (KMC; RFA-RM-16-024), and a Resource Dissemination and Outreach Center (RDOC; RFA-RM-16-025), and potential additional partners. Pending availability of funds, a future initiative may be issued to focus on Cutting Edge Informatics Tools (CEITs).

This specific FOA solicits applications for a KMC component of the IDG Consortium. The KMC will (at a minimum):

• Identify relevant high-quality sources (including literature and databases) that contain significant information about protein targets. Identify suitable abstracts (data, text, graphical information, etc.) from each resource, and make them available to the community via an integrated portal.
• Provide a portal that would be flexible and easy to navigate, support queries that start with any piece of information that is being abstracted in the KMC resource, be able to link to all other pieces of information, and provide link backs into the primary sources.
• Enable community curation, support for executing and incorporating improved analytical pipelines from the IDG or from the outside community.
• Generate a detailed Application Programming Interface (API) to allow programmatic integration of tools created either by the scientific community or putative awardees of a possible future CEITs FOA.
• Engage in outreach activities to improve usage of the resource by the broader biomedical community.
• Enable computations that support the overall goals of the IDG Program on the data and metadata that has been accrued in the Portal.

An example of the types of data and resources (http://pharos.nih.gov/idg/about) and query interface developed for the pilot phase of the IDG can be found here: http://pharos.nih.gov. For this FOA, this pilot phase product serves as an example and awardees are encouraged to re-imagine a solution.

The applicants should possess expertise and capabilities suitable for efficient gathering, analyzing, abstracting, and organizing molecular and functional data on the genes and proteins that would ascribe functions to proteins with a focus on delineating their biological roles in health and disease. It is important to scientifically justify the data types chosen to be included. Some examples of data types include, but are not limited to:

• Omics data (e.g., genomics, proteomics, epigenomics, metabolomics, etc.); tissue specificity of the omic data;
• Model organism data including phenotypes (mammalian and non-mammalian);
• Imaging and physiological data (e.g., X-ray, computed tomography, ultrasound, cellular level imaging, multi-electrode recording, etc.);
• Multiscale data (reflecting diverse levels such as genomic, epigenetic, subcellular, cellular, pathway and interactions, organs, systems, organisms, and populations);
• Data from multiple research areas and diseases (e.g., Genome-wide Association Studies (GWAS), common inflammation pathways in cancer, diabetes, obesity, immune, infectious and neurodegenerative diseases);
• Special considerations for unusual data (e.g., sparse data, heterogeneous data, and/or very large or very small datasets;
• Scientific literature repositories and patent databases; and
• Pharmacological characterizations (e.g., compounds, ligands, antibodies, pharmacokinetics, protein structures, etc.).

The essential elements of the KMC include:

1. Identification of data/knowledge sources: The KMC will provide automated pipelines to extract relevant data and metadata from public sources for the entire proteome. The KMC will be responsible for adding value using human curation to the information gathered, but only for the subset of IDG protein families (i.e., non-olfactory GPCRs, ion channels, and protein kinases). The KMC will include additional relevant data sources as identified by the IDG Steering Committee (SC) or the IDG KMC Project Scientist (PS; See Section VI).

2. Updating information from original sources: The KMC will implement a principled and scientifically justified method for providing updates from original sources. Assigning relative quality metrics to each data-type abstracted from these sources and developing principled ways for implementing such metrics and building community acceptance are core tasks. Establishing data and information provenance at the KMC is an important element of providing a community resource.

3. Database: The KMC will provide data management and retrieval tools for the vast variety of complex biomedical data and knowledge that will be abstracted. Scientifically justified processed data from the primary sources can be stored locally and provided to the community if suitable analytical pipelines can be developed that enhance the interpretation of available data. An example could be improved ways of reconciling tissue expression data obtained from gene and protein expression databases. It is expected that the KMC will store and make available processed data from original resources for addressing specific analytical challenges as identified by the IDG Steering Committee or the IDG KMC PS. This includes acting as a repository of processed data generated by the other components of the IDG Program, as needed.

4. Data Analytics: Given the complexity and specificity of the data types that the KMC will abstract, it is expected that non-KMC scientists (including the broader biomedical community) will play a key role in interpreting the data. The KMC is expected to support analytical pipelines developed in the community (e.g., keeping current with the best method for identifying orthologs so that human genetic information can be mapped to model organism genes/proteins and thus to their phenotypes). Other important analytical capabilities include improving our ability to predict or impute new biological roles for a protein within cells or effecting human health or disease, with a particular focus on supporting efforts by the IDG DRGCs. To this end, the KMC must produce a clear API to allow for data to be exported and new derived data to be imported to the database. This role supporting the DRGCs will include building relevant computational and predictive models (in collaboration with the DRGCs, and future CEIT awardees) that use the data generated at the DRGCs to enhance and support the overall goals of the KMC and the IDG Program.

5. IDG Portal: The KMC will establish a user friendly interface that will support web-based queries as well as provide a modern API and remain current with the standards being developed by the NIH BD2K Program, or as identified by the IDG KMC Project Scientist (See SectionVI for definition). Crucial functions include (1) making available suitable summaries for any protein, including where to find details in other sources and primary literature; (2) visualizing, comparing and identifying knowledge-gaps within an arbitrary subset of proteins or entire protein families; (3) providing access to tools and reagents developed by the IDG Program among others. One main function of the user-interface and API is to help investigators gather preliminary data and evidence in an accessible manner. Facile tools that would support the design of future experiments to clarify the function of understudied targets would be a key deliverable of the KMC. It is reasonable to expect that the data and metadata accrued by the KMC in the IDG Portal will enable a number of computations that could answer questions of relevance to IDG goals e.g., prioritization of targets for deeper study. It is therefore important that data and metadata be accessible in a manner that enables computations. It is expected that the KMC will solicit continuous community feedback and collect usage data on the portal to continue to improve its usability.

6. Outreach to scientific community: A major aim of the IDG Program is to enable the scientific community to efficiently identify understudied proteins and improve our ability to predict their role or function in specific biological or disease conditions. Thus outreach to the scientific community to obtain relevant feedback on the resources developed by the IDG Consortium is essential. While the RDOC awardee will coordinate IDG-wide outreach activities, the KMC should focus on outreach to its users to ensure that its products are useful and maintain the right balance between user-friendliness and sophisticated processing.

Maintenance of existing KMC: At the start of the project, the KMC is expected to seamlessly maintain access to the current pilot phase KMC resource http://pharos.nih.gov and the underlying database(s). Once the new KMC is up and running the pilot KMC resource can be discontinued. There is no expectation to maintain the entirety of the pilot KMC or support all the specific choices made within it. Discontinuation of the legacy KMC can only occur after permission is obtained from the IDG KMC PS.

Participation as Part of a Research Consortium: Groups funded under this initiative will be expected to collaborate effectively with each other to maximize the chances of overall success of the entire IDG Program and to participate in the IDG Consortium. In particular,

• The KMC will work closely with the IDG DRGCs to gather, aggregate, analyze, and present knowledge in a way that facilitates the linking of emergent data around the understudied non-olfactory GPCRs, protein kinases, and ion channels to physiological function and disease relevance.
• The KMC will work with the IDG RDOC and DRGCs to ease community access to resources and tools produced by the IDG and to make similar information about other understudied targets in the IDG protein families available.
• The KMC will work in a coordinated fashion with the IDG RDOC to promote the KMC and IDG Consortium to the broader research community.

All applicants are strongly encouraged to contact NIH program staff identified in this FOA to discuss the alignment of their proposed work with the goals of the FOA and with the IDG Program. A Technical Assistance teleconference will be held for potential applicants to this FOA and companion FOAs on December 13, 2016 at 3:30 PM, EST. NIH staff will present an overview of these FOAs, and NIH program, grants management, and review staff will be available to answer questions from prospective applicants. Details for joining this teleconference can be found here: https://commonfund.nih.gov/idg/index. The information session is open to all prospective applicants, but participation is not a prerequisite to apply.

See Section VIII. Other Information for award authorities and regulations.

NIH grants policies as described in the NIH Grants Policy Statement will apply to the applications submitted and awards made in response to this FOA.

Higher Education Institutions

• Public/State Controlled Institutions of Higher Education
• Private Institutions of Higher Education

The following types of Higher Education Institutions are always encouraged to apply for NIH support as Public or Private Institutions of Higher Education:

o Hispanic-serving Institutions

o Historically Black Colleges and Universities (HBCUs)

o Tribally Controlled Colleges and Universities (TCCUs)

o Alaska Native and Native Hawaiian Serving Institutions

o Asian American Native American Pacific Islander Serving Institutions (AANAPISIs)

Nonprofits Other Than Institutions of Higher Education

• Nonprofits with 501(c)(3) IRS Status (Other than Institutions of Higher Education)
• Nonprofits without 501(c)(3) IRS Status (Other than Institutions of Higher Education)

For-Profit Organizations

• Small Businesses
• For-Profit Organizations (Other than Small Businesses)

Governments

• State Governments
• County Governments
• City or Township Governments
• Special District Governments
• Indian/Native American Tribal Governments (Federally Recognized)
• Indian/Native American Tribal Governments (Other than Federally Recognized)
• Eligible Agencies of the Federal Government Including the NIH Intramural Program
• U.S. Territory or Possession

Other

• Independent School Districts
• Public Housing Authorities/Indian Housing Authorities
• Native American Tribal Organizations (other than Federally recognized tribal governments)
• Faith-based or Community-based Organizations
• Regional Organizations

Non-domestic (non-U.S.) Entities (Foreign Institutions) are not eligible to apply.
Non-domestic (non-U.S.) components of U.S. Organizations are not eligible to apply.
Foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Applicant Organizations

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

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

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

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

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

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

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

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

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

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

This FOA is open to all investigators, including those who are not currently participating in the IDG pilot phase program. Applicants are free to apply to the companion FOAs. However, to encourage participation from a broad representation of the research community, when making funding decisions, NIH intends to consider whether an applicant will be funded as a PD/PI through other IDG FOAs and may choose to limit awards from multiple FOAs. In addition, the IDG Consortium is expected to be open to investigators beyond those funded through the IDG FOAs, as determined by the IDG Steering Committee.

Buttons to access the online ASSIST system or to download application forms are available in Part 1 of this FOA. See your administrative office for instructions if you plan to use an institutional system-to-system solution.

It is critical that applicants follow the Research (R) Instructions in the SF424 (R&R) Application Guide, including Supplemental Grant Application Instructions except where instructed in this funding opportunity announcement to do otherwise. Conformance to the requirements in the Application Guide is required and strictly enforced. Applications that are out of compliance with these instructions may be delayed or not accepted for review.

For information on Application Submission and Receipt, visit Frequently Asked Questions Application Guide, Electronic Submission of Grant Applications.

Although a letter of intent is not required, is not binding, and does not enter into the review of a subsequent application, the information that it contains allows IC staff to estimate the potential review workload and plan the review.

By the date listed in Part 1. Overview Information, prospective applicants are asked to submit a letter of intent that includes the following information:

• Descriptive title of proposed activity
• Name(s), address(es), and telephone number(s) of the PD(s)/PI(s)
• Names of other key personnel
• Participating institution(s)
• Number and title of this funding opportunity

The letter of intent should be sent to:

Jenna Baker, Ph.D.
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Telephone: 301-827-7090
Email: [email protected]

All page limitations described in the SF424 Application Guide and the Table of Page Limits must be followed.

The following section supplements the instructions found in the SF424 (R&R) Application Guide and should be used for preparing an application to this FOA.

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

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

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

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

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

Effective management will require a significant commitment by the Program Director(s)/Principal Investigator(s). For an application proposing a single PD/PI, that PD/PI is expected to devote at least 3 person months annually to the project. If multi-PDs/PIs are proposed, then one PD/PI is expected to commit at least 2 person months annually and the other(s) should devote at least 1 person month each.

Budgets should contain 10% of the total direct costs to fund collaborations with other IDG awardees that advance the overall goals of the Consortium. All these funds are restricted and require NIH prior approval for use. If the NIH IDG Working Group, via the Steering Committee, deems such collaborations scientifically unwarranted, the 10% budget may be re-allocated to the primary project on a yearly basis. A prior approval request is required to re-allocate these funds to other studies.

Budgets should include support for a dedicated Project Manager who will devote a minimum of 6 person months to oversee the day-to-day activities of the project, coordinate across project sites, if applicable, and be responsible for promptly providing requested reporting information to NIH Program Staff. A PD/PI may serve as the Project Manager and if this is the case that person must have at least a minimum of 6 person months of effort devoted to the project.

The IDG Program will have regular conference calls and meetings. Applicants should request funds for 2-6 group members to attend annual meetings, Consortium-led tutorials, and biennial international open innovation meetings organized by the RDOC, as appropriate.

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

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

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

Research Strategy: Applicants should describe plans for a KMC that is capable of handling the breadth and scope of the types of data, metadata, analytical approaches required for extracting and abstracting the broad range of datatypes needed for annotating a protein’s role in a biological or cellular process in health or disease. Applicants should address the following points in the application:

1. Identification of original data/knowledge sources. Applicants should describe

• In a comprehensive table, the sources and types of data that will be collected including prioritization schemes if appropriate.
• How quality standards will be assessed for each resource and how they will be communicated to the users.
• And scientifically justify the choice and use of any human curation that is proposed or other methods to maintain quality. Specify other approaches that will enhance the value of the resource to the community.
• Plans to interact with the IDG Steering Committee and the IDG KMC PS to enhance the coverage of datasets and knowledge beyond what is contained in the original application, in particular to meet the needs of the IDG DRGCs
• Plans to track and store data provenance including versioning as well as a principled approach to tracking and communicating changing biomedical research knowledge about targets.
• Approaches to include data types that are beyond the scientific expertise of the KMC awardees. It is incumbent on the applicant to propose a rigorous approach to incorporate data and analytical engines beyond the expertise of the group the applicant has put together to ensure the quality and reliability of such data types.

2. Updating information from original sources: The applicants should describe:

• Processes for establishing, documenting and publishing data processing pipelines and updating the same.
• Plans for sharing pipelines with the community to enhance rigor, reproducibility, and transparency and working with the IDG SC to develop best practices.
• Plans for quality assessment of the data sources including (if proposed) relative quality metrics between different primary sources and specifically how they plan to resolve the challenges of integrating information from automated pipelines and human curation (if proposed).

3. Database: The applicants should describe:

• And scientifically justify which processed data from the primary sources selected will be stored locally and provided to the community and explain how these plans will be updated to meet the needs of the overall IDG Consortium, in particular the IDG DRGCs.
• Specific analytical pipelines or algorithms to be developed using datasets and the types of scientific queries these pipelines or algorithms will support.
• Analytical pipelines to be obtained from the community and deployed and how the process of selection will be made.
• Since the identity of the experimental components of the IDG Consortium will not be known at the time the application is due, the applicant should describe in general terms how they plan to support abstracted or summarized data generated by the IDG Program (the KMC is not expected to store raw or large amounts of processed data generated by the experimental parts of the IDG Program).

4. Data Analytics: The applicants should:

• Provide a comprehensive table listing the different analytical algorithms they propose to implement. These should address making predictions or imputing and ascribing a function , role in a disease etc. to understudied proteins. Examples of such algorithms that bring diverse data together include: (a) identifying (when possible) the most appropriate model organism ortholog to specific human proteins to enable phenotypic interpretation; (b) utilizing the availability of both gene and protein expression data to validate tissue availability; (c) utilizing GWAS results effectively in prioritizing targets for further study; (d) imputing function to an understudied protein based on similarity to a well-studied target in a data-driven manner using statistical or machine learning algorithms.
• Provide a description for how they will work with the DRGCs to prioritize analytical tool utilization or development to best support the needs of the experimental approaches undertaken by the DRGCs.
• Provide a description of how they will support and deploy the best-in-class algorithms from the community that would help scientists in the IDG DRGCs and broader community prioritize subsets of proteins to work on first.

5. IDG Portal: The applicants should:

• Propose details of a web-based user-interface that will support queries from scientists in the community.
• Explain how the portal and the API together will help investigators within and outside of the IDG gather preliminary data and evidence in an accessible manner to design future experiments that clarify the function or role of understudied targets in biological processes or disease.
• Explain how the portal will support other tools needed to (a) make available suitable summaries for any protein, including where to find details in primary sources; (b) visualize, compare and identify knowledge-gaps within an arbitrary subset of proteins or entire protein families; (c) provide access to reagents and tools developed by the IDG Program.
• Describe how the portal will provide access to data, including link-outs to original data sources, and analytics through a modern API (e.g., REST-based) is essential for the portal.
• Describe how they propose to remain current with the developing standards under the NIH BD2K Program (https://datascience.nih.gov/bd2k), or as identified by the IDG KMC PS.
• Delineate the process, including how the KMC may work with other components of the IDG Consortium, to incorporate continuous feedback from the user community to increase its usability.
• Enable computations on the data accrued by the KMC. Such computations should support development and implementation of the algorithms that support the overall goals of the IDG Program.

6. Outreach to scientific community: A major aim of the IDG Program is to enable the scientific community to efficiently identify understudied proteins and improve our ability to predict their role or function in specific biological or disease conditions. The IDG RDOC will be responsible for coordinating overall outreach activities for the IDG Consortium. Thus the applications should describe in sufficient detail how the KMC will conduct collaborative outreach to the scientific community and how continuous relevant feedback will be incorporated into all parts of the KMC. In particular, the applications should describe how they will use outreach to increase the usability of the Portal. The IDG Portal should provide a means for real-time community feedback on IDG Consortium-produced data and reagents.

Collaborations with IDG Consortium: Applicants should briefly describe their plans to collaborate with the DRGCs and any future CEITs. Applicants should indicate their willingness to explore synergistic collaborations with the DRGCs & any future CEITs once the IDG Consortium is formed.

Additional information applicants should describe in the application:

• Plans to seamlessly maintain access to data and resources from the current pilot phase KMC while the new KMC is being built.
• Plans to transfer the KMC infrastructure, data and analytical tools to any other informatics resource, as designated by the NIH.
• Plans to support and, where necessary, provide training for users.
• Plans to make software modular and robust, and to include appropriate documentation and versioning, so that the broader community can use it as a stand-alone package.
• Plans to employ standard formats for data input and output, to facilitate its use and interoperability with other software including JSON (Java Script Object Notation) or linked data formats.

The following additional items must also be addressed in the application:

• Evidence of Successful Past Performance. Applicants should provide evidence of research productivity as a knowledge management center. Applicants should demonstrate the capacity to scale activities as data volumes or complexity change within a research network.
• Information Technology (IT). Applicants should discuss all pertinent informatics issues involved in providing the basic IT infrastructure/system administration for the proposed project.
• Technology Development. Incremental technology improvements will play an important role in increasing the efficiency and decreasing the cost of the KMC. The applicants are encouraged to include plans for such technology development activities in their applications. Examples include deploying on the cloud, or moving to modern database architectures that enable support for flexible queries, or leveraging other open-source development. The aim of such technology development is to reduce fixed costs and use savings to support validating any predictive algorithms developed by any member of the IDG Consortium and agreed to by the NIH KMC PS. The plans for technology improvement should be well described and the cost of the proposed technology development should be justified in terms of reducing operating costs for the KMC, without disrupting access to the resource.
• Management Plan. The management plan should describe how the PD(s)/PI(s) will manage the proposed project, who will oversee the day-to-day activities (e.g., a Project Manager if not a PD/PI), and how the management structure will support achievement of the proposed goals and milestones. Useful elements of this description include the organization of the proposed project, its management structure, key personnel, and how it will interface with the IDG DRGCs, RDOC, and potential future CEITs and the IDG Steering Committee.
• Milestones and goals. Applications should define a clear set of goals and timeline for the KMC, and annual milestones with metrics that will document progress towards the achievement of the ultimate goals for the IDG Program. Examples include, but are not limited to, milestones that track software development activities, deployment of particular datasets, or the number of defined analyses performed. Applications should include plans for critically evaluating and revising these milestones on a regular basis. Milestones may be revised at the time of the award and/or yearly as described in the terms and conditions of a Cooperative Agreement in section VI.2.

Resource Sharing Plan: Individuals are required to comply with the instructions for the Resource Sharing Plans as provided in the SF424 (R&R) Application Guide, with the following modification:

• All applications, regardless of the amount of direct costs requested for any one year, should include a Resource Sharing Plan.
  
  

Applicants should indicate their willingness to abide by all data deposition, quality control metrics, standardization, metadata requirements, data and software release, and public copyright license policies developed by the IDG SC and approved by NIH staff. A primary goal of the IDG Program is to facilitate discoveries of the broad scientific community for the improvement of public health. Restrictive licensing and sharing practices for IDG-generated data, tools, and resources could substantially diminish their value and public benefit. Accordingly, awardees should manage data, resources, protocols, tools, and software in a way that achieves this goal. Sharing practices that would prevent or block access to or use of IDG program data, tools, and resources for research purposes will be considered to be hindering the goals of the IDG Program. The development of policies, methods, and standards for such sharing is critically important. The NIH expects that the awardees, through the IDG SC, will develop such policies, methods, and standards in concert with the NIH. These policies, methods, and standards will remain consistent with NIH-wide policies on data and resource sharing.

• Specific Plan for Data Sharing: Consistent with achieving the goals of this program, the NIH expects that information such as collected data, technical protocols, and any other metadata collected under this FOA is to be deposited as appropriate into existing, publically available data repositories that are easily accessible, and in machine readable format. Where appropriate, applicants should identify such repositories and plans for deposition. For datatypes that lack suitable public repositories, applicants should indicate their willingness to identify an appropriate alternative solution that is consistent with achieving the goals of the program. Data should also be made available as appropriate via the IDG Portal that will serve as the central access point for information regarding data, critical tools, and reagents being developed by the IDG Consortium. If applicable, applicants must abide by the NIH Genomic Data Sharing Policy (https://gds.nih.gov/) and should indicate their agreement to it in the data sharing plan.
• Specific Plan for Protocol, Tool, and Reagent Sharing: As one of the primary goals of this program is to advance research through development, establishment, broad dissemination and use of community resources across the research community, NIH intends that protocols, tools, and reagents generated by the IDG Consortium be broadly available and distributed at minimal cost, and without undue intellectual property constraints, so that they can be as widely used as possible, thus enabling downstream investigations of understudied proteins by the larger scientific community. For all DRGC applications and where otherwise applicable, the applicant should discuss plans for sharing and distribution of non-data resources that will be generated by the proposed project, including models, protocols, biomaterials, and reagents. The IDG RDOC will work with all IDG Consortium investigators to collect, curate, and disseminate information regarding tools and reagents being developed by the IDG Consortium to be disseminated through the IDG Portal and other sources as appropriate.
• Specific Plan for Sharing Software: A software dissemination plan, with appropriate timelines, is expected in applications that are developing software. 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. A dissemination plan guided by the following principles is thought to promote the largest impact:
• The software should be freely available to biomedical researchers and educators in the non-profit sector, such as institutions of education, research institutions, and government laboratories.
• The terms should also permit the dissemination and commercialization of enhanced or customized versions of the software, or incorporation of the software or pieces of it into other software packages.
• To preserve utility to the community, the software should be transferable such that another individual or team can continue development in the event that the original investigators are unwilling or unable to do so.
• The terms of software availability should include the ability of researchers outside the Center and its collaborating projects to modify the source code and to share modifications with other colleagues as well as with the Center. An applicant should take responsibility for creating the original and subsequent official versions of a piece of software.
• Applicants are asked to propose a plan to manage and disseminate the improvements or customizations of their tools and resources by others. This proposal may include a plan to incorporate the enhancements into the official core software, may involve the creation of an infrastructure for plug-ins, or may describe some other solution.
• Any software dissemination plans represent a commitment by the institution (and its subcontractors as applicable) to support and abide by the plan.
  
  
• To help ensure that the IDG KMC and RDOC can provide comprehensive data and tool sets for each understudied IDG protein, Consortium members will be expected to share complete data and tool sets for the studied proteins, including, as appropriate, any preliminary data and tools from the DRGC application. Sharing preliminary data used in the application will enhance the study of understudied proteins by the larger scientific community and will be consistent with achieving the goals of the program. Applicants should describe which preliminary data would be shared and how.
• Applicants should also be familiar with the NIH statements regarding intellectual property of resources developed with Federal funds (NIH Research Tools Policy (http://grants.nih.gov/grants/intell-property_64FR72090.pdf) and other related NIH sharing policies at http://sharing.nih.gov).
• Prior tofunding, NIH Program Staff may negotiate modifications to the Sharing Plan with the applicant.

Appendix:

Do not use the Appendix to circumvent page limits. Follow all instructions for the Appendix as described in the SF424 (R&R) Application Guide.

When conducting clinical research, follow all instructions for completing PHS Inclusion Enrollment Report as described in the SF424 (R&R) Application Guide.

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

See Part 1. Section III.1 for information regarding the requirement for obtaining a unique entity identifier and for completing and maintaining active registrations in System for Award Management (SAM), NATO Commercial and Government Entity (NCAGE) Code (if applicable), eRA Commons, and Grants.gov

Part I. Overview Information contains information about Key Dates and times. Applicants are encouraged to submit applications before the due date to ensure they have time to make any application corrections that might be necessary for successful submission. When a submission date falls on a weekend or Federal holiday, the application deadline is automatically extended to the next business day.

Organizations must submit applications to Grants.gov (the online portal to find and apply for grants across all Federal agencies). Applicants must then complete the submission process by tracking the status of the application in the eRA Commons, NIH’s electronic system for grants administration. NIH and Grants.gov systems check the application against many of the application instructions upon submission. Errors must be corrected and a changed/corrected application must be submitted to Grants.gov on or before the application due date and time. If a Changed/Corrected application is submitted after the deadline, the application will be considered late. Applications that miss the due date and time are subjected to the NIH Policy on Late Application Submission.

Applicants are responsible for viewing their application before the due date in the eRA Commons to ensure accurate and successful submission.

Information on the submission process and a definition of on-time submission are provided in the SF424 (R&R) Application Guide.

This initiative is not subject to intergovernmental review.

All NIH awards are subject to the terms and conditions, cost principles, and other considerations described in the NIH Grants Policy Statement.

Pre-award costs are allowable only as described in the NIH Grants Policy Statement.

Applications must be submitted electronically following the instructions described in the SF424 (R&R) Application Guide. Paper applications will not be accepted.

Applicants must complete all required registrations before the application due date. Section III. Eligibility Information contains information about registration.

For assistance with your electronic application or for more information on the electronic submission process, visit Applying Electronically. If you encounter a system issue beyond your control that threatens your ability to complete the submission process on-time, you must follow the Guidelines for Applicants Experiencing System Issues. For assistance with application submission, contact the Application Submission Contacts in Section VII.

Important reminders:

All PD(s)/PI(s) must include their eRA Commons ID in the Credential field of the Senior/Key Person Profile Component of the SF424(R&R) Application Package. Failure to register in the Commons and to include a valid PD/PI Commons ID in the credential field will prevent the successful submission of an electronic application to NIH. See Section III of this FOA for information on registration requirements.

The applicant organization must ensure that the DUNS number it provides on the application is the same number used in the organization’s profile in the eRA Commons and for the System for Award Management. Additional information may be found in the SF424 (R&R) Application Guide.

See more tips for avoiding common errors.

Upon receipt, applications will be evaluated for completeness and compliance with application instructions by the Center for Scientific Review and responsiveness by components of participating organizations, NIH. Applications that are incomplete, non-compliant and/or nonresponsive will not be reviewed.

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 the policy.

Only the review criteria described below will be considered in the review process. As part of the NIH mission, all applications submitted to the NIH in support of biomedical and behavioral research are evaluated for scientific and technical merit through the NIH peer review system.

Reviewers will provide an overall impact score to reflect their assessment of the likelihood for the project to exert a sustained, powerful influence on the research field(s) involved, in consideration of the following review criteria and additional review criteria (as applicable for the project proposed).

Reviewers will consider each of the review criteria below in the determination of scientific merit, and give a separate score for each. An application does not need to be strong in all categories to be judged likely to have major scientific impact. For example, a project that by its nature is not innovative may be essential to advance a field.

Does the proposed Center address the needs of the research resource that it will create? Is the scope of activities proposed for the Center appropriate to meet those needs? Will successful completion of the aims bring unique advantages or capabilities to the research resource?

Specific to this FOA: How significant will the resource be to enable the overall goals of the IDG program?

Are the PD(s)/PI(s) and other personnel well suited to their roles in the Center? Do they have appropriate experience and training, and have they demonstrated experience and an ongoing record of accomplishments in managing informatics? Do the investigators demonstrate significant experience with coordinating collaborative basic research? If the Center is multi-PD/PI, do the investigators have complementary and integrated expertise and skills; are their leadership approach, governance, plans for conflict resolution, and organizational structure appropriate for the Center? Does the applicant have experience overseeing selection and management of subawards, if needed?

Specific to this FOA: Do the PD(s)/PI(s) and other key personnel have demonstrated experience in coordinating management and dissemination of the types of datasets that are scientifically needed for a successful KMC and IDG Portal and in working cooperatively in large, distributed scientific projects? Has adequate leadership for the day-to-day project management activities, e.g., a Project Manager and sufficient PD(s)/PI(s) effort to serve the key proposed roles, been described?

Are the concepts, strategies, or instrumentation novel to one type of research program or applicable in a broad sense? Is a refinement, improvement, or new application of scalable organizational concepts, management strategies or instrumentation proposed?

Specific to this FOA: Does the application challenge and seek to shift current research practice paradigms by utilizing novel theoretical concepts, approaches or methodologies? Does the Center efficiently use available tools and resources to accomplish the goals of the project?

Are the overall strategy, operational plan, and organizational structure well-reasoned and appropriate to accomplish the goals of the research resource the Center will create? Will the investigators promote strategies to ensure a robust and unbiased scientific approach across the resource, as appropriate for the work proposed? Are potential problems, alternative strategies, and benchmarks for success presented? If the resource is in the early stages of operation, does the proposed strategy adequately establish feasibility and manage the risks associated with the activities of the resource? Are an appropriate plan for work-flow and a well-established timeline proposed? Have the investigators presented adequate plans to ensure consideration of relevant biological variables, such as sex, for studies of vertebrate animals or human subjects?

Specific to this FOA: Are the datasets identified scientifically justified and would their inclusion lead to a useful resource for the research community and overall long-term goals of the IDG Program (described above in Background)? Are the pipelines that are being proposed well designed, will they be suitable for the task for creating the resource in a timely manner, can they readily accommodate additional data types from the community, and can they appropriately leverage community expertise? Are the choices made for the underlying database technologies and plans for employing standard formats and established ontologies, building data-driven models, data integration, and predictive/imputation models reasonable and appropriate? Has the proposed center identified a rigorous way to incorporate data and analytical engines beyond the expertise of the group the applicant has put together and to track the provenance of data and algorithms and human curation (if proposed)? Are the plans for providing APIs or web services for programmatic access to the KMC data reasonable and appropriate? Are the plans to work closely with other parts of the IDG consortium reasonable and appropriate?

Will the institutional environment in which the Center will operate contribute to the probability of success in facilitating the research resource it serves? Are the institutional support, equipment and other physical resources available to the investigators adequate for the Center proposed? Will the Center benefit from unique features of the institutional environment, infrastructure, or personnel? Are resources available within the scientific environment to support electronic information handling?

Specific to this FOA: Is the computational infrastructure adequate to meet the needs of the project?

As applicable for the project proposed, reviewers will evaluate the following additional items while determining scientific and technical merit, and in providing an overall impact score, but will not give separate scores for these items.

For research that involves human subjects but does not involve one of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate the justification for involvement of human subjects and the proposed protections from research risk relating to their participation according to the following five review criteria: 1) risk to subjects, 2) adequacy of protection against risks, 3) potential benefits to the subjects and others, 4) importance of the knowledge to be gained, and 5) data and safety monitoring for clinical trials.

For research that involves human subjects and meets the criteria for one or more of the six categories of research that are exempt under 45 CFR Part 46, the committee will evaluate: 1) the justification for the exemption, 2) human subjects involvement and characteristics, and 3) sources of materials. For additional information on review of the Human Subjects section, please refer to the Guidelines for the Review of Human Subjects.

When the proposed project involves human subjects and/or NIH-defined clinical research, the committee will evaluate the proposed plans for the inclusion (or exclusion) of individuals on the basis of sex/gender, race, and ethnicity, as well as the inclusion (or exclusion) of children to determine if it is justified in terms of the scientific goals and research strategy proposed. For additional information on review of the Inclusion section, please refer to the Guidelines for the Review of Inclusion in Clinical Research.

The committee will evaluate the involvement of live vertebrate animals as part of the scientific assessment according to the following criteria: (1) description of proposed procedures involving animals, including species, strains, ages, sex, and total number to be used; (2) justifications for the use of animals versus alternative models and for the appropriateness of the species proposed; (3) interventions to minimize discomfort, distress, pain and injury; and (4) justification for euthanasia method if NOT consistent with the AVMA Guidelines for the Euthanasia of Animals. Reviewers will assess the use of chimpanzees as they would any other application proposing the use of vertebrate animals. For additional information on review of the Vertebrate Animals section, please refer to the Worksheet for Review of the Vertebrate Animal Section.

Reviewers will assess whether materials or procedures proposed are potentially hazardous to research personnel and/or the environment, and if needed, determine whether adequate protection is proposed.

Not Applicable

Not Applicable

Not Applicable

As applicable for the project proposed, reviewers will consider each of the following items, but will not give scores for these items, and should not consider them in providing an overall impact score.

Not Applicable

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

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

For consortia involving key biological and/or chemical resources, reviewers will comment on the brief plans proposed for identifying and ensuring the validity of those resources.

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:

• May undergo a selection process in which only those applications deemed to have the highest scientific and technical merit (generally the top half of applications under review) will be discussed and assigned an overall impact score.
• Will receive a written critique.

Appeals of initial peer review will not be accepted for applications submitted in response to this FOA.

Applications will be assigned on the basis of established PHS referral guidelines to the appropriate NIH Institute or Center. Applications will compete for available funds with all other recommended applications submitted in response to this FOA. Following initial peer review, recommended applications will receive a second level of review by The National Cancer Advisory Board . The following will be considered in making funding decisions:

• Scientific and technical merit of the proposed project as determined by scientific peer review.
• Availability of funds.
• Relevance of the proposed project to program priorities.
• Evidence that the applicant and investigators are committed to policies as established by the SC including with regard to confidentiality, sharing of information and resources, and cooperative interaction.
• Evidence of previous productive, cooperative, collaborative interaction.

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. Refer to Part 1 for dates for peer review, advisory council review, and earliest start date.

Information regarding the disposition of applications is available in the NIH Grants Policy Statement.

If the application is under consideration for funding, NIH will request "just-in-time" information from the applicant as described in the NIH Grants Policy Statement.

A formal notification in the form of a Notice of Award (NoA) will be provided to the applicant organization for successful applications. The NoA signed by the grants management officer is the authorizing document and will be sent via email to the grantee’s business official.

Awardees must comply with any funding restrictions described in Section IV.5. Funding Restrictions. Selection of an application for award is not an authorization to begin performance. Any costs incurred before receipt of the NoA are at the recipient's risk. These costs may be reimbursed only to the extent considered allowable pre-award costs.

Any application awarded in response to this FOA will be subject to terms and conditions found on the Award Conditions and Information for NIH Grants website. This includes any recent legislation and policy applicable to awards that is highlighted on this website.

This award is excluded from automatic carryover. All carryover actions require IC prior approval.

The final budget period of this award may not be automatically extended. All extension, including the first, require IC prior approval.

This award is excluded from the Streamlined Noncompeting Award Process (SNAP).

All awards will be incrementally funded for a project period up to 6 years multi-year funded grants will not be awarded under the FOA.

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.

Recipients of federal financial assistance (FFA) from HHS must administer their programs in compliance with federal civil rights law. This means that recipients of HHS funds must ensure equal access to their programs without regard to a person’s race, color, national origin, disability, age and, in some circumstances, sex and religion. This includes ensuring your programs are accessible to persons with limited English proficiency. HHS recognizes that research projects are often limited in scope for many reasons that are nondiscriminatory, such as the principal investigator’s scientific interest, funding limitations, recruitment requirements, and other considerations. Thus, criteria in research protocols that target or exclude certain populations are warranted where nondiscriminatory justifications establish that such criteria are appropriate with respect to the health or safety of the subjects, the scientific study design, or the purpose of the research.

For additional guidance regarding how the provisions apply to NIH grant programs, please contact the Scientific/Research Contact that is identified in Section VII under Agency Contacts of this FOA. HHS provides general guidance to recipients of FFA on meeting their legal obligation to take reasonable steps to provide meaningful access to their programs by persons with limited English proficiency. Please see http://www.hhs.gov/ocr/civilrights/resources/laws/revisedlep.html. The HHS Office for Civil Rights also provides guidance on complying with civil rights laws enforced by HHS. Please see http://www.hhs.gov/ocr/civilrights/understanding/section1557/index.html; and http://www.hhs.gov/ocr/civilrights/understanding/index.html. Recipients of FFA also have specific legal obligations for serving qualified individuals with disabilities. Please see http://www.hhs.gov/ocr/civilrights/understanding/disability/index.html. Please contact the HHS Office for Civil Rights for more information about obligations and prohibitions under federal civil rights laws at http://www.hhs.gov/ocr/office/about/rgn-hqaddresses.html or call 1-800-368-1019 or TDD 1-800-537-7697. Also note it is an HHS Departmental goal to ensure access to quality, culturally competent care, including long-term services and supports, for vulnerable populations. For further guidance on providing culturally and linguistically appropriate services, recipients should review the National Standards for Culturally and Linguistically Appropriate Services in Health and Health Care at http://minorityhealth.hhs.gov/omh/browse.aspx?lvl=2&lvlid=53.

In accordance with the statutory provisions contained in Section 872 of the Duncan Hunter National Defense Authorization Act of Fiscal Year 2009 (Public Law 110-417), NIH awards will be subject to the Federal Awardee Performance and Integrity Information System (FAPIIS) requirements. FAPIIS requires Federal award making officials to review and consider information about an applicant in the designated integrity and performance system (currently FAPIIS) prior to making an award. An applicant, at its option, may review information in the designated integrity and performance systems accessible through FAPIIS and comment on any information about itself that a Federal agency previously entered and is currently in FAPIIS. The Federal awarding agency will consider any comments by the applicant, in addition to other information in FAPIIS, in making a judgement about the applicant’s integrity, business ethics, and record of performance under Federal awards when completing the review of risk posed by applicants as described in 45 CFR Part 75.205 Federal awarding agency review of risk posed by applicants. This provision will apply to all NIH grants and cooperative agreements except fellowships.

Cooperative Agreement Terms and Conditions of Award

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.

Definitions

NIH IDG Working Group (WG): Consists of NIH programmatic staff from multiple Institutes and Centers of the NIH. This group will be primarily responsible for the stewardship of the IDG Program.

Steering Committee (SC): The SC will provide coordination activities for the IDG Program. The SC will include PDs/PIs of each of the awards and NIH IDG WG members. The SC will be chaired by two PD/PIs that are nominated by the SC and approved by the NIH. The SC will establish subcommittees to oversee the development and implementation of consortium policies including data release. The number of NIH votes may not exceed one third of the total number of votes on the SC. The number of votes from a multiple PI award will be one. Votes will inform recommendations to the NIH.

External Scientific Consultants (ESCs): The NIH IDG WG will recruit outside experts (non-awardees) of relevance to the IDG Program to provide advice to NIH. The NIH IDG WG may solicit from the ESCs input on progress made by individual awardee, progress made towards the overall goals of the IDG Program, and any changes in scope or governance that might help the make the output of the IDG Program more effective and useful to the biomedical community.

IDG Consortium: The IDG Consortium will be made up of IDG awardees, the NIH IDG WG and other scientists and groups the SC agrees to include within the Consortium. The Consortium structure is meant to enable the overall goals of the IDG Program.

The PD(s)/PI(s) will have the primary responsibility for:

• Determining research approaches, designing protocols, and setting project milestones.
• Conducting the scientific research in the project, reporting progress and milestones or objectives to NIH staff, reporting results to the scientific community, and disseminating approaches, methods, and tools broadly.
• Working with the RDOC and other awardees to maximize impact of the IDG Program and meet program goals and objectives.
• Agreeing to the governance of the IDG Consortium through the SC and the NIH IDG WG, including accepting approved recommendations from the ESCs.
• Actively participating in the IDG SC, including attending both in-person and teleconference meetings, and participating in collaborative activities and subcommittees. At least one in-person SC meeting will be held per year, for which IDG awardees will pay the travel for their attending members.
• Updating goals and milestones at the time of award and providing summaries of progress toward those goals at least yearly, as requested by NIH. The milestones will be reviewed annually (and at other times, if necessary), and new milestones will be negotiated, as needed by working with the NIH IDG WG and Project Scientists as appropriate.
• Ensuring that data are deposited in a timely manner in the appropriate public databases as agreed upon by the IDG SC and approved by the NIH IDG WG. Ensuring that software and other tools and resources developed as part of this project are made publicly available according to IDG policies, and that results of the project are published in a timely manner.
• Agreeing to abide by any policies -- including those regarding intellectual property, data and software release, publication of IDG Consortium papers, quality control metrics, standardization, metadata requirements, and public copyright licensing -- that are recommended by the IDG SC and approved by the NIH IDG WG, as well as applicable NIH policies, laws, and regulations.
• Being prepared for annual administrative site visits by NIH staff.
• Agreeing to participate in the collaborative activities of the Consortium, and agreeing not to disclose confidential information obtained from other members of the IDG Consortium.
• Awardees will retain custody of and have primary rights to the data and software developed under these awards, subject to Government rights of access consistent with current DHHS, PHS, and NIH policies.

NIH staff has substantial programmatic involvement that is above and beyond the normal stewardship role in awards, as described below:

NIH Program Officer

• A NIH Program Officer (PO) will provide the standard programmatic oversight and stewardship of the projects, including review of pre-award and award documents/requirements, review of progress reports and budgets, and any other programmatic issues that may arise.
• Has the option to recommend, following consultation with the NIH IDG WG, the withholding or reduction of support from any project that substantially fails to achieve its goals according to the milestones agreed to at the time of the award. NIH reserves the right to withhold funding or curtail an award in the event of: (a) Substantive changes in the project, or failure to make sufficient progress toward the project milestones, including timely pre-publication deposition of data or reagents in accordance with approved Sharing Plans; or (b) Ethical or conflict of interest issues.

NIH Project Scientists

• One or more NIH Program Staff will serve as Project Scientists (PSs), for each IDG award and, as appropriate, to oversee collaborative projects amongst IDG awardees and/or other Consortium members. The PS will serve as the scientific representative of the NIH to the investigators in accordance with policies and procedures of the cooperative agreement mechanism. If there is more than one PS, one of them will be designated as the Lead PS. The PSs will provide substantial NIH scientific programmatic involvement with the awardee that is anticipated during the performance of the activities supported by this Cooperative Agreement, including review of milestones.
• The NIH IDG WG will provide final assessment, review, and approval of IDG project milestones and any renegotiation.

Other NIH Program Staff

• May serve on sub-committees of the IDG SC, as needed. The staff will assist the IDG SC in developing operating guidelines and consistent policies for dealing with situations that require coordinated actions.
• Will help the IDG SC members to coordinate the group process of exchanging information about research approaches and protocol designs and of developing additional IDG policies.
• Will serve as liaisons between the awardees and the ESCs, the Office of Strategic Coordination (Common Fund), and the NIH Institute and Center Advisory Councils.
• Will review and approve, in consultation with the ESCs (as needed), recommendations and plans provided by the IDG SC for collaborative activities amongst IDG awardees or outside groups.

Areas of Joint Responsibility include:

Close interaction among the participating investigators will be required, as well as significant involvement from the NIH, to develop the IDG Implementation Phase. The awardees, the PSs, and other designated NIH Staff will participate in the annual in-person SC meeting and scheduled conference calls and share information on data resources, methodologies, analytical tools, as well as data and preliminary results. PDs/PIs, key co-investigators and pre- and post-doctoral trainees, especially those who are members of under-represented minority groups or those from different but related disciplines, are eligible to attend these meetings. ESCs will attend the annual in person meetings. Other government staff may attend the IDG SC meetings.

The IDG SC will serve as the main scientific body of the IDG, with the following roles:

• The SC will be responsible for coordinating the activities of the IDG projects and is the committee through which the NIH IDG WG formally interacts with the IDG investigators. SC membership will include the PI(s) of each Project, (limited to one vote for a Project with multiple PIs) and NIH staff appointed by the NIH IDG WG (voting limited to one third of total SC votes). The IDG SC Chair(s) will be appointed by the NIH and drawn from the individual project PIs. The IDG SC may add additional, non-voting, members, as needed.
• The SC will develop a plan to generate, promote, and maintain a name awareness of the IDG Program and the IDG Consortium, including making decisions on names for outward-facing components of IDG Consortium efforts such as, but not limited to, the IDG Portal.
• The SC may choose to open Consortium membership to collaborators not funded through the IDG Program, provided that such members agree to abide by policies enacted by the SC. The SC may generate additional conditions that apply to non-awardee members of the Consortium.
• The IDG SC may set up subcommittees as needed to address particular issues. These subcommittees will include representatives from the IDG and the NIH and possibly other experts. The IDG SC will have the overall responsibility of assessing and prioritizing the progress of the various subcommittees. It is anticipated that multiple subcommittees may need to be formed, for example, to address topics such as:
• Data and Reagent Deposition and Sharing
• Quality Control and Validation
• Publications and Outreach
• Under direction of the SC, NIH staff and each awardee will be responsible for outreach. Outreach includes advertising IDG resources (including the KMC, Consortium-generated data and material resources) to potential users in both the public and private sectors. Outreach will include providing letters of support in applications proposing to use IDG-generated resources and applications proposing illumination of ion channels, non-olfactory GPCRs, and protein kinases that have been identified by IDG as understudied.

External Scientific Consultants (ESCs):

• The ESCs will provide input and advice to the NIH IDG WG. This could include reviewing and evaluating the progress of the entire IDG Program or individual awardees as well as recommending changes in priorities for the IDG Program based on scientific advances within and outside of the IDG Consortium. The ESCs will be senior, scientific experts who are not directly involved in the activities of the IDG Program. NIH will appoint the ESCs. The NIH IDG WG, and other NIH staff may attend executive meetings with the ESCs.
• The ESCs will meet at least once a year in conjunction with a meeting of the IDG Consortium. The ESCs may also meet by phone or web at others times of the year, as needed.
• Annually, the ESCs will provide individual assessments to the NIH of the progress of the IDG Consortium and will present recommendations regarding any changes in the IDG Program as necessary. The assessments and recommendations will be provided through the IDG WG to the Director of the Office of Strategic Coordination, NIH.

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 will be convened. The panel will have three members: a designee of the SC chosen without NIH staff voting, one NIH designee, and a third designee with expertise in the relevant area who is chosen by the other two; in the case of individual disagreement, the first member may be chosen by the individual awardee. This special dispute resolution procedure does not alter the awardee's right to appeal an adverse action that is otherwise appealable in accordance with PHS regulation 42 CFR Part 50, Subpart D and DHHS regulation 45 CFR Part 16.

When multiple years are involved, awardees will be required to submit the Research Performance Progress Report (RPPR) annually and financial statements as required in the NIH Grants Policy Statement.

A final progress report, invention statement, and the expenditure data portion of the Federal Financial Report are required for closeout of an award, as described in the NIH Grants Policy Statement.

The Federal Funding Accountability and Transparency Act of 2006 (Transparency Act), includes a requirement for awardees of Federal grants to report information about first-tier subawards and executive compensation under Federal assistance awards issued in FY2011 or later. All awardees of applicable NIH grants and cooperative agreements are required to report to the Federal Subaward Reporting System (FSRS) available at www.fsrs.gov on all subawards over $25,000. See the NIH Grants Policy Statement for additional information on this reporting requirement.

In accordance with the regulatory requirements provided at 45 CFR 75.113 and Appendix XII to 45 CFR Part 75, recipients that have currently active Federal grants, cooperative agreements, and procurement contracts from all Federal awarding agencies with a cumulative total value greater than $10,000,000 for any period of time during the period of performance of a Federal award, must report and maintain the currency of information reported in the System for Award Management (SAM) about civil, criminal, and administrative proceedings in connection with the award or performance of a Federal award that reached final disposition within the most recent five-year period. The recipient must also make semiannual disclosures regarding such proceedings. Proceedings information will be made publicly available in the designated integrity and performance system (currently FAPIIS). This is a statutory requirement under section 872 of Public Law 110-417, as amended (41 U.S.C. 2313). As required by section 3010 of Public Law 111-212, all information posted in the designated integrity and performance system on or after April 15, 2011, except past performance reviews required for Federal procurement contracts, will be publicly available. Full reporting requirements and procedures are found in Appendix XII to 45 CFR Part 75 Award Term and Conditions for Recipient Integrity and Performance Matters.

We encourage inquiries concerning this funding opportunity and welcome the opportunity to answer questions from potential applicants.

eRA Service Desk (Questions regarding ASSIST, eRA Commons registration, submitting and tracking an application, documenting system problems that threaten submission by the due date, post submission issues)
Finding Help Online: http://grants.nih.gov/support/ (preferred method of contact)

Telephone: 301-402-7469 or 866-504-9552 (Toll Free)

Grants.gov Customer Support (Questions regarding Grants.gov registration and submission, downloading forms and application packages)
Contact Center Telephone: 800-518-4726

Email: [email protected]

GrantsInfo (Questions regarding application instructions and process, finding NIH grant resources)
Email: [email protected] (preferred method of contact)

Telephone: 301-710-0267

Jean C. ZenKlusen, Lic.Chem., Ph.D.
National Cancer Institute (NCI)
Telephone: 301-451-2144
Email: [email protected]

Mark Caprara, Ph.D.
Center for Scientific Review (CSR)
Telephone: 301-613-5228
Email: [email protected]

Sean Hine
National Cancer Institute (NCI)
Telephone: 240-276-6291
Email: [email protected]

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

Awards are made under the authorization of Sections 301 and 405 of the Public Health Service Act as amended (42 USC 241 and 284) and under Federal Regulations 42 CFR Part 52 and 45 CFR Part 75 .