ENCODE 2011 RFA Frequently Asked Questions (FAQ)

ENCODE 2011 RFA Frequently Asked Questions (FAQ)

• General Questions
• Questions about RFA-HG-11-024
• Questions about RFA-HG-11-025
• Questions about RFA-HG-11-026

General Questions

Letters of intent are due one month before the application receipt date (Nov 6 or Nov 21)

Letters are not required, but help with review.

Prospective applicants are strongly encouraged to submit by e-mail, either with letter of intent or preferably earlier, a short (~1 page) description of plans so that we can discuss and provide feedback to make sure plans are within the scope of NHGRI's interest.

Can intramural investigators submit a grant application in response to this RFA? Can they participate in ENCODE?

NIH intramural researchers are NOT eligible to apply for these FOAs.

Researchers with other funding sources may apply for membership in the ENCODE Consortium or specifically the ENCODE Analysis Working Group if they agree to abide by Criteria for Participation (see http://www.genome.gov/encode/#al-3 for details).

Are the Dec 6th/21st due dates the posted or receipt dates?

Since these are RFAs, all applications must be received by the due date (whether paper – U54/U41 or electronic – U01)

Do we need to send in a request for approval to submit a budget in excess of $500k in direct costs per year?

Since these are RFAs, there is no need to send a request to submit a budget in excess of $500,000 direct costs, but budgets must be well justified.

Is analysis of a minimum set of marks for ENCODE, or ENCODE data quality, a U41/Data Analysis Component activity, a U01 activity, or both?

Both RFAs include this as a potential activity. All Consortium members will be expected to work together to avoid unnecessary duplication of effort.

Will there be future Technology Development [R01] type FOAs as part of ENCODE?

NHGRI does not have plans right now for any additional solicitations for technology development beyond the RFAs that were issued this summer. Generally speaking, technology development for high-throughput methods to find and validate functional elements is also supported by investigator-initiated R01 grants. Please contact an ENCODE Program Director with a summary of your proposed research and we will provide guidance on the appropriateness for NHGRI.

RFA-HG-11-024: Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Model Organisms (U54)

NOTE: NOT-HG-12-001 provides clarification to research scope language.

Are multiple PIs allowed for this RFA?

No, multiple PIs are not permitted for this RFA in order to achieve tight overall management. PIs must devote at least 3 calendar months (25%) effort to this project.

Is a simple statement agreeing to abide by the current ENCODE data release policy and whatever future policy is adopted by the ENCODE Consortium sufficient to address the section on data release?

No. All applicants must provide a specific proposal for release of production data and are encouraged to address the issue of release of data analyses as well as indicate a willingness to participate in the development of a final plan and to accept it. Applicants should review the Resource Sharing Plan described in section IV.2 in the RFA.

How much biological validation is appropriate for a U54?

This should be limited to minimum required to demonstrate that the high-throughput methods being used actually find elements with the functional activity ascribed to the method. The RFA suggests that this should be no more than $300,000 direct costs per year, but scale and budget must be well justified. Should be conducted as soon as possible to provide feedback, not lag until the end of the project.

Do the applicants for a production center have to be in one geographical location?

No, however a strong management plan that addresses this issue should be described in the application.

Can U54 projects propose analyses of existing datasets to identify functional elements instead of focusing on experimental data generation and analysis?

The RFA does solicit for projects that provide annotations of the human and mouse genomes by improving gene models. Other types of analysis efforts would be more appropriate under the RFA HG-11-025 or as unsolicited R01s.

Will the next phase of ENCODE still focus on Tier 1 and 2 cell lines? What justification is needed to propose other cell types? Should the application describe a sample acquisition component or will samples be provided centrally?

The next phase of ENCODE has a goal to provide a comprehensive catalog of functional elements using existing technologies. For functional elements of broad utility such as open chromatin, methylation, histone modifications, and transcript maps, a comprehensive catalog will require assays in many different cell types. Given the larger number of sequence-specific transcription factors and RNA-binding proteins, these assays should only be done in a smaller number of cell types with a minimum of two cell types. Once funded, the ENCODE Consortium will continue to work on the Tier 1 and 2 cells as appropriate and expand to include additional cell types needed to complete the catalog. Each application should propose the cell types that they feel are necessary to complete the catalog. These additional cell types will need to be justified by the value that these data will add to the catalog. NHGRI will not have a centralized sample acquisition resource although once applications are funded and decisions are made about new cell types, the Consortium will try to coordinate sample acquisition so that each project works on the same samples.

RFA-HG-11-025: Computational Analysis of the Encyclopedia of DNA Elements (ENCODE) (U01)

Are multiple PI applications allowed?

Yes

Do you need to be a member of the ENCODE Consortium to submit a U01 application?

Absolutely not. We are looking to bring more people in to provide analysis methods to enhance the ENCODE catalog.

Can one applicant apply for both the U41 Data Analysis (DA) Component and a U01 Data Analysis award?

There is no rule against this. However, the idea behind the U01 awards is to include researchers that are independent of the EDCAC and having applicants on both projects would defeat this goal.

Would an application that focused on a specific disease or cell-type be appropriate?

Applications should propose analysis methods that are generalizable and not focus on hypothesis generation with a single biological focus.

Can an investigator submit an application in response to this FOA while s/he is also part of a team applying for RFA-HG-11-024 "Expanding the Encyclopedia of DNA Elements (ENCODE) in the Human and Model Organisms"?

Any investigator can submit an application for RFA-HG-11-025 regardless of whether s/he is involved with another application for a different RFA. The RFA-HG-11-024 does allow for integrative analyses but these should be limited to those important for assessing the quality of the data produced in its own center. Broader integrative analyses can be performed by researchers funded under RFA-HG-11-025. Data analysts funded under RFA-HG-11-025 do not necessarily need to be associated with a data production center.

Will the U01 projects be part of the Analysis Working Group (AWG) for the ENCODE Consortium.

The U01 projects will be members of the ENCODE Consortium once the awards are funded. As members of the Consortium, they will be asked to share methods and results. Since these awards are more focused on research topics, NHGRI will not require quarterly progress reports and they do not have to be part of the AWG which has a focus on providing a resource, the comprehensive catalog of functional elements. Any U01 project can join the AWG if they are interested. If an analysis pipeline from a U01 project is of value to the AWG, the AWG may ask to incorporate it into their analysis methods.

Will the U01 projects be expected to have the same data release policy as the (U54) production awards?

The ENCODE Project is a community resource project and NHGRI encourages a data release policy with rapid release of the verified data that is of value to the research community. However, the U01 projects may be more focused on research topics and therefore may not initially generate stable analysis datasets. The current ENCODE data release policy does not address the release of integrative data analyses. A policy for release of these datasets will be developed by the Consortium once the next phase of ENCODE begins. All applicants must provide a specific proposal for the release of data analyses as well as indicate a willingness to participate in the development of a final plan and to accept it. Applicants should review the Resource Sharing Plan described in section IV.2 in the RFA.

Can the U01 projects include an experimental component?

Biological validation of computational predictions often adds value to define the accuracy of a computational approach. Therefore, an experimental component is permitted but should be limited to providing biological validation. Experiments to generate new datasets for analysis will not be supported.

Should the focus of a U01 application be on the ENCODE data?

The U01 projects should develop and implement methods to enhance the ENCODE data. So the baseline is to use ENCODE data. Projects may propose to integrate ENCODE data with other datasets to increase the value of the ENCODE data.

What if there is an overlap between ideas proposed by the U01 projects and activities currently done by members of the ENCODE Consortium?

Like any NIH application, the applicant will need to define a significant problem and an approach that will result in significant improvements in the state of the art. All funded projects will be members of the ENCODE Consortium and the expectation is that members will share information on their projects and come to an agreement on preventing an overlap in approaches.

RFA-HG-011-026: Data Analysis and Coordination Centers for the Encyclopedia of DNA Elements (ENCODE) Project (U41)

Are multi-PI applications allowed?

No, multiple PIs are not permitted for this RFA. PIs must devote at least 3 calendar months (25%) effort to this project.

Can one applicant apply for both the U41 Data Analysis Component and a U01 Data Analysis award?

There is no rule against this. However, the idea behind the U01 awards is to include researchers that are independent of the EDCAC.

Are there limits to the types of analyses allowed in the DAC?

The U41 awards are to support a resource, not for research. Therefore, the emphasis on the EDCAC should be on the generation of the ENCODE catalog of functional elements. Applications should focus on robust, stable activities that are essential for this catalog and the users’ interpretations of the catalog. Activities that involve research into methods to derive insights into biological processes or disease mechanism should be supported by another mechanism such as the U01 FOA (RFA-HG-11-025) or an unsolicited R01.

What sort of timeline do you expect before the DC and/or DA is "up and running"?

The EDCAC components should be up and running as soon as possible. There should be only a very short amount of time for ramp up. Therefore, applicants need to demonstrate the appropriate experience and expertise, and that the institute they work in has the capacity and ability to do this scale of work from the start of the project.

Will applying to both the DC and DA components, and elucidating in the applications the specific interactions between these two components, hamper being considered for each component individually? In other words, if applying for both, should the applications emphasize working together or being able to work with any other applicant selected?

All applicants should describe potential interactions with the other component of the EDCAC. These interactions should be described in general terms since the identity of the other component is not known. Applicants are allowed to submit for both components but must do so in separate applications. Only in this situation, the applications can refer to specific interactions between the components.

Regarding evidence of past performance, at what level is this necessary? The PI? Collaborators? The Institute or Company?

The application review process evaluates the Principal Investigator, the environment, and the management plan. Therefore, all of these components contribute to the reviewers’ evaluation of the project.

What is the expected data release policy for the U41 components?

The ENCODE Project is a community resource project and NHGRI encourages a data release policy with rapid release of the stable data that is of value to the research community. For the data coordination component, since they are responsible for the release of ENCODE data through the ENCODE Portal, they must provide plans for rapid release of submitted data to the public. For the data analysis component, the current ENCODE data release policy does not address the release of integrative data analyses. However, the NHGRI feels that stable integrative analyses that are of value to the community should be released rapidly prior to publication. The final data release policy for the ENCODE Consortium, including the release of integrative analyses, will be developed by the Consortium once the next phase of ENCODE begins. All applicants must provide a specific proposal for the release of data analyses as well as indicate a willingness to participate in the development of a final plan and to accept it. Applicants should review the Resource Sharing Plan described in section IV.2 in the RFA.

What is the limit of analysis into the biological function of the functional elements that the DA component should perform? Can the DA component propose an experimental component?

The data analysis component should focus on analyses that are needed to improve on the utility of the catalog. Assigning biological roles to functional elements through integrative analysis of the data serves to increase the resolution of the catalog. However, analyses should not focus on a particular biological problem but more on the goal to annotate comprehensively the genome. The DA component supports the AWG in their analysis activities. The DA component should not propose an experimental component since any biological validation experiment should be proposed by the AWG and support for these experiments would be discussed by the Consortium.

Last Reviewed: February 4, 2012