Revved-up epigenetic sequencing may foster new diagnostics : Nature Medicine : Nature Publishing Group
Revved-up epigenetic sequencing may foster new diagnostics
- Nature Medicine
- Published online
The promise of epigenetic therapy has captured the imagination of the biomedical field ever since 2004, when US regulators approved Vidaza (azacitidine). The drug, manufactured by New Jersey–based Celgene, is a chemical analog of the cytosine nucleoside used in DNA and seems to treat blood-related diseases known as myelodysplastic syndromes by modifying the epigenetic elements of genes involved in regulating the cell cycle. But only a handful of such therapies have made it to the market in the decade that has followed, in part, researchers say, because it remains difficult to efficiently decipher where and how molecules known as methyl groups leave their epigenetic mark on a particular gene.
One limitation of many epigenetic analytical methods is that they provide only the percentage of base pairs in a given sample that have methyl groups attached, rather than the specific locations of those modifications. Whole-genome sequencing can yield more precise methylation maps, but these tests cost thousands of dollars and can take weeks to complete.
Now, several innovations described in recent months could allow researchers to find where methyl groups lie on specific genes more cheaply and more quickly than this process usually requires—an essential advancement if researchers are to determine the cause of certain life-threatening diseases and develop drugs that can suppress these gene-silencing groups. “There is some hidden information that is not yet being captured,” says Paul Soloway, a biochemist at Cornell University in Ithaca, New York, who works on technologies for epigenetic profiling. “So, it's important to think ahead and try to break down current barriers.”
One example comes from Roche NimbleGen, a Wisconsin-based division of the Swiss pharmaceutical giant Roche that is building a machine that can detail the epigenetic modifications on short fragments of DNA. At the American Society of Human Genetics annual meeting in Boston in October, the company unveiled a new method called SeqCap Epi that can generate the same high-resolution data that one can obtain from whole-genome epigenetic analysis but for smaller targets ranging from 10,000 to 75 million base pairs in size. According to Daniel Burgess, a senior scientist at Roche NimbleGen, this provides an inexpensive way of capturing epigenetic data in a high-throughput fashion for researchers who might only be interested in a subset of the genome. “We have the only practical method for making sufficient probes for targeted enrichment,” he says.
“The general idea is innovative,” says Xian Chen, a biochemist at the University of North Carolina at Chapel Hill. “The fact that you can handle a significantly higher number of samples to achieve power is vital for human studies,” adds Paula Desplats, a neuroscientist at the University of California–San Diego. According to Burgess, the SeqCap Epi system could hit the consumer market as early as this month.
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