NEW YORK (GenomeWeb) – The National Human Genome Research Institute announced that it intends to award up to $38 million in grant funding in fiscal year 2017 to help expand the scope of its ENCODE Project, both in terms of functional genomic element data it generates and how it analyzes and disseminates those data.
Specifically, the agency will soon begin accepting grant applications around five new initiatives designed to expand the program's catalog of functional elements; move toward a general understanding of the roles of these genomic elements in different contexts; develop strategies to apply the program's findings to disease; increase the number of researchers participating in the project; and develop and disseminate new analytical tools to improve the value of ENCODE data.
ENCODE, shorthand for ENCyclopedia Of DNA Elements, was launched in 2003 to identify all functional elements in the human genome and freely share the data with the scientific community in accessible and interpretable formats.
Thus far, ENCODE collaborators have identified various putative functional elements — including genes, RNA transcripts, DNA-encoded regulatory elements, and regulatory elements acting at the RNA level — using a variety of genomic methods based on biochemical assays. As of late last year, the project has released approximately 3,500 experiments, each containing at least two replicates, examining approximately 300 human cell types, as well as roughly 1,000 experiments in more than 150 mouse cell types, according to the NHGRI.
These data are also being integrated into an encyclopedia of candidate functional elements to facilitate the study of the roles of functional elements in disease and basic biological processes.
Based on recommendations made during a workshop held in early 2015 to consider future directions for the ENCODE Project and areas where additional work is required, the NHGRI has now issued five new funding opportunities around research that will help the project meet new goals.
Under the first, the NHGRI will award $15.5 million to $20 million in fiscal 2017 to fund between six and eight Mapping Centers that will create comprehensive catalogs of candidate functional elements in the human and mouse genomes in an expanded number of cell contexts compared to those studied to date in the ENCODE project.
Of particular interest to the NHGRI are projects mapping transcribed regions, chromatin accessibility, histone marks, sites of DNA methylation, long-range chromatin interactions, and various relevant chromatin proteins. It is also seeking projects to map the binding sites of RNA binding proteins and sequence-specific transcription factors not previously studied in ENCODE in a small number of biological contexts so as to identify binding motifs.
Additional details about this FOA can be found here.
The second ENCODE funding opportunity focuses on projects to develop and apply new and generalizable methods for characterizing candidate functional elements identified using ENCODE data.
"These projects may characterize function along the continuum from molecular phenotypes … to organismal phenotypes," the NHGRI said. They may also use defined cell systems such as primary cells or model organisms in particular biological contexts for in-depth studies.
Centers participating in this work are expected to collaborate to identify a generalizable approach for characterizing candidate functional elements. Therefore, grant recipients are encouraged to reserve part of their experimental capacity to test a common set of elements across the multiple funded characterization centers.
The NHGRI expects to provide $5.9 million to $6.5 million to fund seven to 10 of these projects in fiscal 2017. Additional details can be found here.
Through the third funding opportunity, the NHGRI will commit $2.5 million to $3 million to fund four to six projects to develop and apply novel statistical, mathematical, and computational methods for improving on analysis, visualization, or interpretation of ENCODE data.
Although projects should focus on analysis activities that use existing ENCODE data, they may include the integration of these data with those from ongoing disease-mapping studies. Examples of projects appropriate for this funding opportunity include, but are not limited to, modeling and predicting element function or gene-element relationships; visualization or interpretation of high-dimensionality data; and the use of ENCODE data to functionally annotate putative causal variants.
Details of this funding opportunity are available here.
The NHGRI also aims to fund the establishment of a data-coordination center and a data-analysis center, which will operate together to gather ENCODE data and metadata, integrate them with genome sequences, and act together as a unified resource to help researchers access ENCODE data, tools, and methods, as well as create and disseminate the encyclopedia of candidate functional elements.
The first center will be tasked with providing data management functions and coordinating consortium activities, while the second will perform and lead integrative analyses needed to produce the candidate functional element encyclopedia.
The NHGRI expects to commit between $5 million and $5.5 million in fiscal 2017 to fund the data-coordination center, and between $2 million and $3 million for the data-analysis center. Additional details can be found here and here.