The NIH has unveiled new grants to advance genome sequencing, many of which focus on nanopore sequencing.
The National Human Genome Research Institute (NHGRI), part of the NIH, awarded $14.5 million in grants in August to eight groups of researchers in industry and academia who are working to make genome sequencing speedier, more accurate, and more informative.
Thanks to next-generation techniques, the cost of sequencing a human genome has plunged by more than 99% in less than 10 years, and now runs as low as $1,000. Plummeting prices have opened up numerous opportunities for researchers, such as sequencing full tumor genomes to uncover gene variants that drive abnormal growth. But for clinical uses, “it's still more expensive than you want it to be for an individual patient,” says Mark Akeson, PhD, of the University of California Santa Cruz Genomics Institute, who received one of the grants.
The awards are the most recent—and the last—from the NHGRI's Advanced DNA Sequencing Technology program, which began in 2004. Over the last 10 years, the program “has in my opinion been just critical for advancing sequencing technology,” says Jay Shendure, MD, PhD, of the University of Washington in Seattle, who's also a grant recipient.
Four grants went to researchers who are seeking to improve what may be the next big thing in genome sequencing: nanopore sequencing. Next-generation sequencing involves breaking up DNA into small chunks that can be less than 100 bases long. Copying and sequencing the pieces produces “reads,” and software assembles the jumble of reads into a full genome. Nanopore sequencing, in contrast, works by reeling DNA strands through tiny holes, or nanopores, in a lipid layer or other material. An electrical current passes through each nanopore, and as the DNA strand moves through the pore it causes characteristic changes in the current that allow researchers to determine the identity of the DNA bases.
Research labs already perform nanopore sequencing, and the first commercial device, the size of a flip phone, is being beta tested. The advantage of nanopore sequencing is that it provides longer reads that are easier to assemble into a final sequence.
Akeson's lab plans to test how well nanopore sequencing recognizes DNA methylation and other epigenetic modifications in the human and mouse genomes. Changes in the pattern of these modifications can have key roles in cancer—for example, tumor suppressor genes are often heavily methylated in cancer cells. However, standard next-generation methods remove the modifications, Akeson notes.
Shendure's team is developing techniques that fill in information that next-generation sequencing skips. For instance, next-generation sequencing can't reveal the haplotype, or which gene variants occur together on the same chromosome copy.
However, he and his colleagues were able to the reconstruct the haplotype for the entire genome of the famous HeLa cell line by sequencing a library containing large DNA fragments. With their grant, Shendure's team hopes to make techniques like this one cheaper and easier to use. “Thousand-dollar genomes are only 90% complete,” he says. “What we are trying to do is get you that last 10%.”
NHGRI is planning future grants that could fund more work on DNA sequencing technologies.
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- ©2014 American Association for Cancer Research.