Characterizing the Functional Elements in the Encyclopedia of DNA Elements (ENCODE) Catalog (UM1) | Apply Online

Frequently Asked Questions (FAQs)

What is the title of this NIH funding opportunity?

The funding opportunity is titled "Characterizing the Functional Elements in the Encyclopedia of DNA Elements (ENCODE) Catalog (UM1)" (RFA HG 16-003).

Which agency is offering this grant opportunity?

This opportunity is offered under the U.S. Department of Health and Human Services (HHS), National Institutes of Health (NIH).

What funding mechanism does this opportunity use?

It uses a cooperative agreement mechanism (UM1), which indicates substantial NIH involvement and active coordination with funded teams.

What is the main goal of this program?

The core goal is to move ENCODE findings beyond biochemical annotation (signals that correlate with function) toward direct experimental evidence of biological function (causal roles) for candidate functional DNA elements.

What problem is this FOA trying to address?

ENCODE has identified many candidate functional DNA regions based on biochemical signatures (like transcription factor binding or chromatin accessibility), but most have not been experimentally tested to confirm whether they truly have functional roles in cells, development, or disease. This FOA targets that gap between correlation and causation.

What kinds of DNA elements are in scope?

Candidate functional DNA elements from the ENCODE catalog are in scope, including regions associated with measurable biochemical signatures such as transcription factor binding, chromatin accessibility, histone modifications, or transcriptional activity.

What types of functional roles are projects expected to test?

Projects are expected to experimentally test what candidate elements actually do, which may include determining whether a region functions as an enhancer, promoter, insulator, silencer, or another type of regulatory element.

Does the FOA emphasize context-dependent function?

Yes. A major theme is that regulatory activity may depend on biological context, such as cell type, developmental stage, environmental conditions, or disease state. Projects are expected to help determine when and where candidate elements are functional.

Are projects expected to focus on one gene or one locus?

No. The program prioritizes approaches that are generalizable, meaning they can be applied across many genomic elements and across multiple biological contexts, rather than being limited to one gene, one locus, or a narrow experimental system.

What kinds of experimental work are expected?

Projects are expected to use one or more experimental assays to characterize function. The FOA also emphasizes comparing and benchmarking assays across awardees to understand their strengths, weaknesses, and practical tradeoffs.

How does the FOA define the difference between biochemical annotation and functional evidence?

Biochemical annotation refers to signatures that correlate with function (for example, protein binding or chromatin marks). Functional evidence refers to experimental tests showing that changing a candidate element causes measurable effects on molecular or cellular phenotypes, supporting a direct biological role.

Is genetic variation a major focus of this opportunity?

Yes. A major emphasis is testing how genetic variation affects element function, including naturally occurring human variants and engineered variants created through experimental manipulation.

What types of variants are specifically mentioned?

The FOA mentions naturally occurring variants found in human populations, including variants implicated by genome-wide association studies (GWAS), as well as engineered variants introduced experimentally.

What kinds of outcomes might be measured when variants or elements are altered?

Applicants are encouraged to examine molecular phenotypes such as gene expression, chromatin state, transcription factor occupancy, and higher-order genome organization, as well as downstream cellular phenotypes relevant to health and disease.

Does the FOA encourage using disease contexts?

Yes. The FOA encourages the use of human diseases or well-chosen biological systems as rigorous test cases where functional assays can be evaluated for their ability to explain or predict phenotype.

How does this program relate to interpreting noncoding variation?

A stated intent is to strengthen the bridge between noncoding/regulatory variation and human disease mechanisms by producing functional evidence that helps interpret variants outside protein-coding regions.

Is this opportunity intended to be a consortium effort?

Yes. It is structured as a coordinated, consortium-style effort rather than isolated grants, with awardees expected to participate in the ENCODE Consortium.

What collaboration expectations are described?

Awardees are expected to work together to compare and benchmark the assays supported by the program, helping identify robust and scalable approaches and clarifying sensitivity to experimental conditions.

What is meant by "benchmarking" in this FOA?

Benchmarking refers to comparing the performance of different functional characterization methods across assays and contexts to clarify strengths, weaknesses, tradeoffs, and which approaches are most informative for particular classes of candidate elements.

What shared deliverables or outcomes does the FOA anticipate?

In addition to producing new data, the FOA anticipates outcomes such as clearer guidance on interpreting functional claims from different experimental strategies and the identification of a set of well-characterized functional elements in healthy and/or disease states.

What is the "reference set" described in the FOA?

The FOA anticipates identifying a set of well-characterized functional elements (in healthy and/or disease states) intended to serve as a resource for understanding regulatory element behavior and for validating future computational and experimental predictions.

What is the expected broader impact of this program?

The expected impact includes clarifying which ENCODE-labeled candidate regions have real biological roles (and under what conditions) and improving the functional genomics toolbox to better support interpretation of genetic variation relevant to human disease.

What is the activity category and CFDA number listed?

The activity category is Health, and the CFDA number is 93.172.

Who is eligible to apply?

Eligibility is broad and includes various government entities, public and private institutions of higher education, nonprofit organizations (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and additional applicants as clarified in the FOA.

When was this opportunity posted and when did it close?

The opportunity was posted and created on January 15, 2016, and the closing date was March 21, 2016.

Does the UM1 cooperative agreement imply NIH involvement after award?

Yes. The UM1 cooperative agreement mechanism signals substantial NIH involvement and coordination with funded teams, consistent with the consortium-style structure described.

What makes a proposed approach align with the FOA's priorities?

Based on the description, aligned approaches are generalizable across many elements and contexts, use experimental assays to establish functional (causal) roles, test context dependence, examine impacts of genetic variation, and contribute to consortium benchmarking and shared resources.