Frequently Asked Questions for IGVF RFAs

At what stage should an applicant contact NHGRI about research ideas?

Applicants may contact NHGRI at any stage, from initial ideas to detailed specific aims. A summary of ideas or preferably a draft of specific aims would be a good starting point. This should describe what you propose to study, the aims of the study, and why it is important to the field and the goals of the IGVF Consortium. These should not exceed one page in length.

Can I apply to more than one RFA?

Yes.  Applicants can apply to more than one of the IGVF RFAs.  However, when making funding decisions, NHGRI intends to consider whether an applicant will be funded as a PD/PI through other IGVF RFAs and may choose to limit awards from multiple RFAs to encourage participation from a broad representation of the research community. NHGRI will also consider how scientifically distinct the applications are to one another and the applicant’s role in each application (e.g., PI/MPI, co-investigator, collaborator, etc.).

I would like to focus on a specific disease system. Is this appropriate for these RFAs?

Projects may employ disease-relevant systems if the proposed findings and approaches will be generalizable to a number of diseases.  Focus on a single disease is non-responsive to RFA-HG-20-043 and RFA-HG-20-045.

Year 1 is a planning year for the IGVF Consortium in which budgets for RFA-HG-20-043, RFA-HG-20-045, RFA-HG-20-046, and RFA-HG-20-047 are reduced in the first year. For these RFAs, should effort requirements for PIs/MPIs and project managers also be reduced?

No. The effort requirements for PIs/MPIs and project managers are identical for all funded years. These personnel are expected to be engaged in the collaborative effort of consortium planning.

If year 1 is primarily a planning year for the consortium, should applicants budget for experiments and computational analyses during year 1?

Yes, applicants can and should budget funds for data production and computational analyses during the first year, especially while planning to work with other components. Some of the expected consortium and RFA-specific activities for year 1 are outlined in the RFAs and should be considered when proposing and budgeting for the first year. This may include setting up and optimizing assays in collaboration with other projects and centers and contributing to the consortium’s study design amongst other activities.

Does the Specific Aims page have to mirror the RFA-specific subsections?

No. A separate Specific Aims page is required for each of the RFAs. Proposed specific aims do not have to exactly match the RFA-specific subsection headings.

Does the Research Strategy Section need to have the standard subsections of “Significance, Innovation, and Approach” in addition to the RFA-specific subsections?

No. However, significance, innovation, and approach must be addressed somewhere in the Research Strategy section. For example, significance could be addressed in the Overview subsection, while innovation and approach are addressed elsewhere in the Research Strategy. Another example is to address the significance, innovation, and approach in the Overview subsection, followed by expansion of these points in the subsequent subsections. For the RFA-specific subsections in RFA-HG-20-043, RFA-HG-20-044, RFA-HG-20-046, and RFA-HG-20-047, these subsections may be changed, but the content described under each must be addressed in the Research Strategy. In RFA-HG-20-045, the RFA-specific subsections must be used.

How should innovation be addressed?

This will vary and depend on the RFA. For Networks and Modeling RFAs, applicants may propose to develop new approaches, where the level of innovation in the approach development will be a consideration. For the Mapping and Characterization RFAs, approaches and technologies are expected to be well-developed and robust. Innovation may be assessed in how these technologies are applied for the study of the proposed systems.

How detailed should plans for collaborative activities be?

At the time of this application, the identity of the other funded awards will not be available.  Applicants should suggest conceptual ideas of how they could work with other members of the consortium, but details are not required. These plans should indicate to application reviewers and NIH program how applicants are thinking about collaboration.

Is partnering with applicants for a different IGVF RFA ahead of application submission encouraged?

Groups that are interested in applying to different IGVF RFAs can interact with each other or have overlapping personnel ahead of application submission. It is not recommended to propose a project that is dependent on another project being funded. However, a group could include language in their application that addresses if another project is funded, how they would work with that other group. 

Can you explain more about the variant/element/phenotype catalog and how it will be developed?

The development of this catalog will be a consortium effort. The Modeling Projects and Characterization Centers will co-lead a collaboration to develop this catalog. Other projects and centers, including the DACC, will assist and contribute to catalog development. The DACC will host the catalog as part of the consortium-developed data resource that will be made accessible to the broader community.  The consortium will develop the framework during the planning year.

For studies proposing variants, would the study of structural variants be responsive?

Applicants are free to propose variants as they see fit and find appropriate for their proposed research and should explain their rationale for variants chosen for study.

Can human fetal tissue be used in proposed studies?

There are special considerations for human fetal tissue use in NIH projects. For more information about NIH policy see NOT-OD-19-128. Also see the FAQs page for human fetal tissue research.

Are mammalian model systems other than human and mouse considered responsive for these RFAs?

For the Mapping and Characterization RFAs, mammalian systems are limited to mouse and human. For the Networks RFA, research in human systems is preferred. Use of non-human mammalian systems may be allowed but must be justified by potential to learn about the impact of genomic variation on networks substantially beyond what could be accomplished using human systems, and by transferability of research findings and outcomes to studies of human health and disease.

Can NIH intramural investigators be involved in an IGVF application?

Yes, intramural investigators may serve as co-investigators, collaborators, and consultants on applications. Salary support is not allowable, but limited costs pertaining to supplies, equipment, and project staff may be allowable. Intramural investigators should check with their ICs about extramural collaboration guidelines. For more information see the NIH Policy on Intramural/Extramural Collaborations.

Can foreign institutions apply?

Foreign institutions may apply to RFA-HG-20-043, RFA-HG-20-044, RFA-HG-20-045, and RFA-HG-20-047. Foreign institutions are not allowed to apply to RFA-HG-20-046, but foreign components, as defined in the NIH Grants Policy Statement, are allowed.

Does NHGRI anticipate any smaller FOAs (R01/R21) to arise through IGVF in the near future?

NHGRI cannot talk about any FOAs that are under development and not currently public. However, the scientific topics addressed in IGVF are central to NHGRI’s mission, so work on similar topics could be appropriate for standalone R01s or R21s.  Please reach out to NHGRI program staff to discuss your ideas and how they may fit in at NHGRI.

For this RFA, how much emphasis should be placed on the assessment of variant and/or element function at the level of molecular, cellular, and organismal phenotypes?

Applicants should consider which and at what percentage of a project these different levels of phenotypes are appropriate for the proposed study and justify these choices in their applications.

For this RFA, can an applicant propose to study multiple cell types in one organ if the data generated is applicable to multiple diseases?

Yes, this would be responsive. NHGRI expects a diversity of approaches, cell types, and samples to be funded through this RFA.

Is a proposal to study a diverse population (e.g., different mouse strains) as a source of naturally occurring perturbations responsive?

No. This RFA requires the introduction of interventions and/or perturbations, not an observational study of standing genetic variation.

For this RFA, can more than three assays be proposed?

Mapping Centers must be able to support data generation utilizing 2-3 distinct single-cell assays; one of these assay types must be single-cell transcriptomics. If additional assays are proposed, they should be well-justified.

Can applicants propose to perform functional validation studies within their Mapping Centers?

No. Functional validation and characterization are out of scope for this initiative. Candidate functional elements identified by Mapping Centers may be tested in later years in collaboration with IGVF Functional Characterization Centers, as appropriate. 

Can a Mapping Center propose to use a perturbation in proposed studies?

Although perturbations such as a drug, hormone, or gene knockout may be allowable, these should be used to map genomic features, at single-cell resolution, relevant to particular cell types, states and fates. Perturbations may also be used to generate a greater diversity of cell types. For specific questions about allowable perturbations, applicants should contact NHGRI program staff.

What are the differences between the Mapping RFA and the Regulatory Networks RFAs?

Mapping Centers are primarily focused on generation of a resource of gene and regulatory maps while Regulatory Network Projects are focused on research predicting and testing relationships between variants, elements and genes at the network or systems level.

For the Predictive Modeling RFA can predictive modeling methods include analysis of coding variants and non-coding variants?

Yes. Coding and non-coding variation are in scope for predictive modeling.

What type of variants would be responsive to this RFA?

IGVF will allow investigation of genetic and genomic variants in a broad sense. Predictive modeling projects have flexibility in the type(s) of genetic/genomic variants they propose to study and should explain the rationale for their proposed choices. NHGRI is interested in predictive modeling approaches that complement work carried out by the functional characterization centers. Review of the characterization RFA (RFA-HG-20-043) is encouraged since these two components will work closely together.

Can predictive modeling projects use public datasets in their modeling efforts?

Yes. As the consortium starts to produce data, modeling projects will be expected to work closely with the consortium and use consortium-generated data. During the planning year, predictive modeling projects will work with consortium members and contribute to plans for experiments and data collection that will inform modeling project efforts.

What is the difference between the Predictive Modeling RFA and the Networks RFA?

Regulatory network projects will include experimental/wet-lab data generation, computational network modeling, and experimental testing of model predictions. Predictive modeling projects will include developing computational approaches to model and predict relationships among variation, functional elements, genome function, and phenotype. Modeling projects should not include substantial experimental/wet-lab data generation, but may propose limited experimental work (<10% of direct costs) to inform modeling efforts.

Can network projects start generating data at full effort in year 1 or will they be required to wait for completion of consortium year 1 planning?

Network projects can start generating data at full effort during year 1 and are not required to wait until a consensus plan emerges from the year 1 consortium planning.

What are the expectations for regulatory network projects to work with other components of IGVF?

Regulatory network projects will have opportunities to collaborate with other funded projects and centers, especially in the later years of IGVF. Applicants should consider and propose how they could work with other IGVF components, but regulatory network projects should not be dependent upon such interactions.

Is spatial data essential for the Networks RFA?

One of the goals of this RFA is to leverage advances in technology to gain insight into gene regulatory networks. Applications to this RFA should include data collection methods with spatial and/or temporal resolution. NHGRI program staff should be contacted if applicants have specific questions.

What type of spatial data would be considered responsive to this RFA?

There are no required data types. Imaging data indicative of phenotypes, spatial transcriptomics, or information on cell-cell interactions are examples of potentially useful data to model.

For the Networks RFA, can methods include analysis of coding variants and non-coding variants?

Yes. Coding and non-coding variation are in scope for network projects.

Is proposal of a project that is entirely computational responsive to this RFA?

No. Regulatory network projects must include experimental/wet-lab data generation, computational network modeling, and experimental testing of model predictions.

Can public datasets be used for computational aspects of network projects?

Public datasets can be used, but experimental data generation is a required component of regulatory network projects.

Are protein interaction networks responsive to this RFA?

Protein-protein interaction (PPI) networks are not the focus of this RFA. PPI networks could be part of a larger regulatory network project. Study of a particular protein complex is non-responsive. NHGRI program staff should be contacted for specific questions.

Is collection of both single-cell data and spatial data responsive to this RFA?

Collecting data derived from single-cell approaches and data that has spatial and/or temporal data are goals of this RFA.

Should applicants propose the use of in vivo or in vitro systems for this RFA?

Applicants may propose either or both types of systems. They should be clear about the rationale for the use of the proposed system(s) and the utility of these in generating regulatory network models.

What is the difference in scope between the Networks RFA (RFA-HG-20-044) and the Characterization RFA (RFA-HG-20-043)?

The Characterization RFA is primarily experimental and is focused on high throughput perturbation of non-coding or protein-coding variants and/or elements and assessing changes in phenotypes. Regulatory network projects must include experimental/wet-lab data generation, computational network modeling, and experimental testing of model predictions. The computational component is a key part of the regulatory networks RFA that is not in the scope of the Characterization RFA.  

Is prior experience in running a DACC required for this RFA?

No. Prior experience in running a DACC is not required. However, applicants must demonstrate experience working in collaborative environments and coordination of large genomics data research efforts and have demonstrated experience with administrative management of research and/or resource-based efforts.

Are there specific requirements for the type of computational infrastructure developed by the DACC?

Applicants should consider the resources that are currently being used for housing data resources, expected computational needs of the IGVF Consortium, user experience, and accessibility of different types of platforms. Include an explanation of these tradeoffs to justify your choice in the application. Applicants should consider that a primary goal is to produce a scalable data resource suitable for both machine learning and human-guided data exploration.