Abstract
The National Human Genome Research Institute has earmarked up to $38 million in grant funding for five new initiatives aimed at expanding ENCODE, its database of functional elements in human and mouse genomes. For the first time, grantees will focus on diseased tissue samples in an effort to understand how these functional elements influence the development of cancer and other diseases.
The National Human Genome Research Institute (NHGRI) in Bethesda, MD, has earmarked up to $38 million per year over four years to fund grants for its public research project, the Encyclopedia of DNA Elements (ENCODE). The new grants will fund five new initiatives aimed at expanding ENCODE's database and developing new tools to facilitate analysis and dissemination of the data.
ENCODE was launched by NHGRI in 2003 to identify and catalog all functional elements of the human genome previously mapped by the Human Genome Project and make its data easily accessible to the public. The institute is now turning some of its focus to analyzing these cataloged elements and determining their roles in human biology and disease, says Elise Feingold, PhD, program director of Genome Analysis at NHGRI and leader of the ENCODE project.
The new four-year grants, to be awarded in fiscal year 2017, will be divided among the following priorities, says Feingold:
$15.5–$20 million per year for 6–8 Mapping Centers that will use high-throughput experiments to continue cataloging candidate functional elements in human and mouse genomes, from a broad range of cell sources.
$5.9–$6.5 million per year for 7–10 projects focused on characterizing candidate functional elements in specific biological contexts.
$2.5–$3 million per year for 4–6 projects to develop new computational methods aimed at improving ENCODE data analysis and interpretation.
$5–$5.5 million per year for a data coordination center and $2–$3 million per year for a data analysis center; both will serve as a consolidated resource for researchers wishing to access ENCODE data and analyses.
Unlike past ENCODE projects, the new grants will include “specifically looking at diseased tissue samples,” says Feingold, which is “a whole other avenue for discovery of functional regions of the genome.” For example, some DNA elements are functional only in the cancer setting and would not be revealed by studying normal tissue.
“Cancer researchers are using ENCODE data to learn about the role of somatic and germline variation, and trans-acting regulators involved in cancer,” says Mike Pazin, PhD, a program director of functional genomics at NHGRI, who helps oversee ENCODE. To date, he adds, ENCODE data have been used by researchers outside of ENCODE in about 1,300 scientific papers—about 500 associated with specific diseases, and 180 involving cancer.
For example, Yotam Drier, PhD, a postdoctoral fellow at the Broad Institute in Cambridge, MA, investigates transcriptional deregulation in cancer, and two of his recently published studies used ENCODE data. In one study, Drier and his colleagues identified super-enhancer translocations that drive overexpression of MYB, an oncogenic transcription factor, in adenoid cystic carcinoma. In the second study, the researchers described novel mechanisms of enhancer-driven activation of the oncogenes MYC and BCL6 in lymphoma.
“In recent years, there has been an explosion of whole cancer genome sequences, but it has been difficult to understand all the alterations, because these genomic regions are not well annotated,” says Drier. “ENCODE is doing the fundamental work of providing characterizing data, such as enhancers, transcription factor binding sites, and histone modifications across both normal and cancer cells.”
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