Clinical OMICS

MAR-APR 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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30 Clinical OMICs March/April 2017 www.clinicalomics.com Data & Informatics I n 2003, the Encylopedia of DNA Elements (ENCODE) project was launched with hopes of creating a com- prehensive catalog of all the coding and noncoding elements in the human genome . This February, the National Human Genome Research Institute (NHGRI), a part of the National Insti- tutes of Health, announced that they would provide the funds to support ENCODE for four more years . All new data generated by the newest phases of the project will be released into public databases and will be available through ENCODE's Data Coordina- tion Center . Over a decade ago, when the Human Genome Project was com- plete, researchers realized that despite being able to read all three billion base pairs in the human genome, they understood very little about how the genome functioned . Since only 2% of the genome coded for proteins, the rest was thought to be nonfunctional DNA . However, scientists quickly realized that these noncoding regions contained elements that played a cru- cial role in gene expression . "The ENCODE project was launched with the goal to actually be able to functionally annotate the human genome—the rest of the 98% that we call 'dark matter,'" said Yin Shen, Ph . D . , a professor in the depart- ment of neurology at the University of California, San Francisco (UCSF), and one of the grant recipients . "I think now [there are] a lot of tools being developed, particularly in recent years, that allow us to start dis- secting the function of the dark matter of the genome," Dr. Shen said. Accord- ing to Dr . Shen, these include massive parallel reporter assays, CRISPRCas9, and 3D genome structure assays such as HiC (a method for investigating the higher-order DNA folding, a cru- cial component of gene regulation) . ENCODE's expanded efforts will include five characterization centers at four institutions—UCSF, Stan- ford University, Cornell University, and the Lawrence Berkeley National Laboratory—where researchers will use some of these tools to shed light on how the regulatory elements in the genome influence gene expression and cell function . Shen, along with her colleague Bing Ren, Ph . D, at the University of California, San Diego, will use a high-throughput CRISPRCas9 method to conduct large-scale functional validation screens of the regulatory sequences in the mammalian genome . "The hope is that by interrogating tens of thousands of regulatory sequences, we'll have enough power to discover the features that can be used to predict the functional regulatory DNA ele- ments in the genome and as a result we will gain better abilities of read- ing the grammar in our genetic blue- print," Dr. Shen noted. Another grant went to Nadav Ahituv, Ph . D . , a professor in the department of bioengineering and therapeutic sciences at UCSF and his collaborator, Jay Shendure, M . D . , Ph . D . , a professor of genome sciences at the University of Washington (UW) . With a previous ENCODE grant, Dr . Ahituv's and Dr . Shendure's labs developed a massive parallel reporter assay that could test thousands of Decoding the Dark Genome The NHGRI Funds Four More Years of the ENCODE Project for Researchers to Investigate the Regulatory Elements of the Human Genome Diana Kwon, Contributing Editor "I think now [there are] a lot of tools being developed, particularly in recent years, that allow us to start dissecting the function of the dark matter of the genome." —Yin Shen, Ph.D., University of California, San Francisco

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