NIH Extends Support for Genomics Catalog

The NIH announced earlier this month that it has issued new awards totaling up to $31.5 million in fiscal year 2017 for its Encyclopedia of DNA Elements (ENCODE) Project. The funds will expand the catalog of candidate gene regulatory elements and support new efforts to characterize biological roles of the candidate elements in various cell types and model systems. Additionally, project awards will allow the ENCODE catalog to incorporate data provided by researchers and will allow the use of biological samples from research participants who have agreed to share their genomic data. The resource is available to researchers free of charge at www.encodeproject.org.

“We're broadening the scope to try to better understand the catalog we're generating,” says Elise Feingold, PhD, a program director at the National Human Genome Research Institute, part of the NIH.

As cancer disease drivers continue turning up in oft-ignored noncoding stretches, ENCODE “could shine a light on this ‘dark matter’ and allow researchers to pay more attention to these parts of the genome,” says Bing Ren, PhD, an investigator at the Ludwig Institute for Cancer Research at the University of California, San Diego. Ren co-leads one of ENCODE's newly funded characterization centers, which will study gene regulatory elements in a range of biological contexts. Other centers include the University of California, San Francisco (UCSF); University of Washington in Seattle; Stanford University in Palo Alto, CA; Cornell University in Ithaca, NY; and Lawrence Berkeley National Laboratory in CA.

Since ENCODE launched 14 years ago, researchers not funded by ENCODE have published more than 1,700 papers using its data and tools. Roughly one third of these publications focus on disease applications, says Feingold, and about a third of those relate to cancer.

ENCODE helps scientists form or refine hypotheses about the biological underpinnings of susceptibility alleles identified by genome-wide association analyses. In a study published last fall, researchers used the genomics catalog to identify tissue-specific effects of two APOBEC3 germline variants in bladder and breast cancers (Nat Genet 2016;48:1330–8). Also last year, ENCODE helped scientists discover a surprising mechanism behind certain gliomas: Mutations in IDH, which encodes an enzyme involved in energy production, trigger local hypermethylation that disrupts the regulation of the oncogene PDGFRA (Nature 2016; 529:110–4).

Some of the new ENCODE funding goes toward functional validation using newly developed tools, such as a high-throughput version of CRISPR/Cas9 to study the consequences of deleting tens of thousands of genomic elements at a time, in parallel, says Ren, who co-leads this effort with UCSF's Yin Shen, PhD. Another group, led by Mark Gerstein, PhD, of Yale University in New Haven, CT, is developing a tool called FunSeq, available at http://funseq.gersteinlab.org, to prioritize the impact of mutations in noncoding regions.

Despite the utility of ENCODE resources, some researchers worry that the growing number of “big science” initiatives could deplete NIH funding for investigator-driven projects. “This top-down approach opens the door for insider influence” in choosing topics and soliciting grant applications, says Robert Waterston, MD, PhD, chair of genome sciences at the University of Washington in Seattle.

To be useful to a wide range of investigators, ENCODE is “fairly agnostic” about what biological samples are studied, Feingold says. “The primary goal is to make this resource freely available to the community to study the genetic basis of disease and gene regulation.” –Esther Landhuis

For more news on cancer research, visit Cancer Discovery online at http://cancerdiscovery.aacrjournals.org/content/early/by/section.