Genomics 2012: Narcissomes, Neonates and ENCODE

By Kevin Davies 

January 2, 2013 | FIRST BASE | From clinical exomes to the clamor over the ENCODE Project, 2012 was a packed year for genomics in both the research and clinical arena, and seemingly sets the stage for a barnstorming, anniversary-rich 2013. 

It was the year that clinical exome sequencing emerged as a viable and increasingly popular offering for medical centers and diagnostics companies. From Baylor to the Mayo Clinic, UCLA to Emory, academic centers fell over themselves to offer clinical exome sequencing services, ripe with the possibility of ending diagnostic odysseys. 

Earlier this year we profiled Ambry Genetics, the California diagnostics company that signaled a sea change in clinical genomics with the launch of its CLIA Exome sequencing service 13 months ago. Last summer, I received a note from noted medical geneticist James Lupski, chastising me for not checking out what was going on in Houston at the Baylor Whole Genome Laboratory (WGL).  

Last June, WGL held a party to celebrate the completion of its first 100 clinical exomes, a number that swelled to more than 700 by the end of the year. In more complex cases, a large team of medical genetics experts convene in a genome interpretation grand rounds. The hope is for more outcomes similar to that of Nicholas Volker, who following the end of his diagnostic odyssey, can finally attend school and celebrate Halloween with his friends. 

Establishing best practices in clinical genome interpretation was the cause of the CLARITY Challenge, organized by Boston Children’s Hospital, the results of which were presented at the American Society of Human Genetics conference in November. Although I was skeptical about the rationale of this contest when it was first being discussed (in part because of the precedent of the Volker case), I commend the organizers, winners, and all 23 participants for sharing their ideas and, in at least one case, ending the diagnostic odyssey of a young boy named Adam, much to the delight of his mother. 

One of the highest profile stories of the year was that of Jay Shendure’s team at the University of Washington in predicting a fetal genome sequence using a non-invasive capture of fetal DNA. (A similar result was published by Stanford’s Stephen Quake and colleagues a month later.) Writing in Science Translational Medicine, Shendure and colleagues cautioned that “although the noninvasive prediction of a fetal genome may be technically feasible, its interpretation—even for known Mendelian disorders—will remain a major challenge.” 

Shendure is an advisor to Ariosa, one of a handful of companies that have launched commercial non-invasive fetal screening tests for trisomy 21 and other conditions during the past 12 months, including Verinata, Natera, and Sequenom. Obviously there is a huge chasm between trisomy detection and full fetal sequencing, but it will be fascinating to see where how far the technology and ethical debate progresses in 2013.  

In a related story, Stephen Kingsmore and colleagues at Mercy Children’s Hospital in Kansas City collaborated with Illumina to demonstrate the feasibility of rapid (50-hour) genome sequencing of infants in the neonatal intensive care unit. 

Personal genome analysis was taken to extremes by two high-profile scientists in—where else?—California. Stanford’s Mike Snyder has conducted a battery of genomic tests on himself. His claim that genomic variants that predisposed him to type 2 diabetes proved uncannily accurate when a viral infection pushed him into that medical diagnosis. Snyder’s voyage of sequence self-discovery earned him the “narcissome” label.  

In some ways, however, Snyder has a ways to go in the digital health arena to match the admirably obsessive Larry Smarr, director of Calit2. 

In the year between 10^th anniversary genome celebrations (2011 marking the tin anniversary of the publication of the first draft papers, while next year marks 10 years since the official declaration of the project’s completion), the human genome was dissected as never before in an extraordinary series of 30 peer-review publications—the ENCODE Project. 

Team leader Ewan Birney took a quite unjustified amount of criticism over the media coverage of the work, complete with many sensational headlines about the newly discovered function of ‘junk DNA.’ Perhaps dissatisfied with the media’s coverage of the project, Birney left nothing to chance: he decided to interview himself, eliciting a candid and informative assessment of the project’s strengths and weaknesses. 

DTC Deals 

Just a few years ago, there were at least four promising companies vying for the direct-to-consumer genome analysis market. And now there is one… 

Pathway Genetics is still offering genome tests, but in consultation with doctors. deCODEme has long since been priced into irrelevancy, and the recent $415-million Amgen deal appears to leave no room for a consumer genetics play. Meanwhile Navigenics was purchased by Life Technologies for its CLIA-certified laboratory and software interface.  

That leaves 23andMe, which celebrated an infusion of $50 million with a price drop to just $99 and a pledge to push the number of clients from around 200,000 currently to the coveted 1 million mark. 

2013 will see a number of fascinating issues play out on the commercial front. Complete Genomics hopes to wrap up its acquisition by BGI (which has been deemed acceptable in principle by the US Government), while Illumina and another party are circling. Amgen’s $415-million purchase of deCODE will strengthen its R&D pipeline, leaving open the question of whether there are other assets at the Icelandic company yet to emerge. 

And many in the next-gen sequencing space will be hoping that Oxford Nanopore’s physical presence at ASHG, even though they weren’t saying much, will be a prelude to the commercial launch of a truly disruptive sequencing technology. Fittingly, these issues will play out against a backdrop of April celebrations of the 60^th anniversary of the double helix and the 10^th anniversary of the Human Genome Project.  

Several events marking these anniversaries are already announced, including the 2013 Bio-IT World Conference in Boston, Genomic Disorders 2013 in Cambridge, UK (featuring James Watson), and a symposium at NHGRI on April 25 (‘DNA Day’), entitled: The Genomics Landscape a Decade after the Human Genome Project.