By Aaron Krol and Allison Proffitt
September 30, 2013 | The 5th annual Consumer Genetics Conference (www.consumergeneticsconference.com) wrapped up last Friday in Boston, after three days of rich discussion, new ideas and products, and a bit of debate.
kicked off the event with a summary of his personal odyssey to identify his daughter’s rare genetic disease (see, Hugh Rienhoff Cops a Candidate Gene in His Daughter’s DNA
). Though Beatrice’s exact condition has not been named, but she carries a TGF-beta 3 mutation that, with Rienhoff’s prodding, has prompted more research. Rienhoff’s journey has been a long one, but every step has added a bit more information to the broader picture. Rienhoff says that he made progress not because of who he knew, but because of a willingness to talk to people, and to endure the snubs and polite rejections along the way. Rienhoff champions patient (and parent) involvement. “It's very unrealistic that we can rely on geneticists going forward,” he said. “We're all going to have to become geneticists.” Today, there is a mouse model with Beatrice’s specific mutation under study—and one of its line lives a pampered life in Bea’s bedroom. Rienhoff continues his search looking for “other Beatrices.” He says: “My hope is to find a group of octogenarians with TGF-beta-3 mutations.”
Dr. Robert Green, director of the genomes2people research program at Brigham and Women’s Hospital and Harvard Medical School, presented the initial findings of the Impact of Personal Genomics (PGen) Study, a large-scale survey of genetic testing consumers led by Dr. Green and Scott Roberts of the University of Michigan School of Public Health. PGen gathered participants from users of the 23andMe and Pathway Genomics genetic testing services, and asked them questions at three different intervals: before they received their test results, 1-2 weeks after, and 6 months after. Questions were designed to explore both the motivations that led consumers to seek out personalized genomics services, and how they perceived and acted on their results afterward. Anxiety, perception of disease risks, and changes in personal health behaviors were all examined in the survey, which also delved into the demographics of those who choose to undergo genetic testing. In addition to his work with PGen, Dr. Green is also head of the MedSeq Project, an NIH-funded program that delivers the results of genetic tests direct to clinicians in a readable one-page format, and is involved in the spinoff BabySeq, which will soon do the same with neonatal sequencing.
, Director of the Laboratory for Molecular Medicine at Partners HealthCare Center for Personalized Genetic Medicine, discussed her ongoing work with the ClinVar database to standardize how the results of genetic tests are presented to patients. As genomic testing grows more routine, rare variants are regularly discovered and flagged as potentially pathogenic, leading to conflicting or tenuous conclusions about pathogenicity that may be passed on to patients. ClinVar, administered through the National Center for Biotechnology Information at the National Library of Medicine, seeks to centralize the evidence for the pathogenicity of these variants, assemble expert evaluations of the evidence, and standardize how that information is presented. Variants in the database are described as either pathogenic, likely pathogenic, uncertain, likely benign or benign, with links that allow users to view the relevant literature and curation process. Relying on large quantities of data, ClinVar takes a middle ground between being open source and relying on the gatekeeping of expert analysis: anyone can submit data, but that information will be assigned to different levels of curation depending on how many studies have examined a particular variant, and whether an expert panel has been assembled to reach consensus on its pathogenicity. ClinVar has so far assembled information on around 50,000 variants, about half from sources that were not previously publicly available. On September 25
, the NIH announced an $8.25 million grant to Rehm’s team to continue their work with ClinVar.
Taking on the issues of scale, Daniel MacArthur, co-founder of Genomes Unzipped, said, “We are dominated by artifacts of variant calling.” On one hand, we don’t have enough data. MacArthur said that the industry is only just beginning to fully grasp the scope of differentiating between a true rare variant and artifacts in samples that are simply not large enough to know. On the other hand, of course, storage is expensive and in some cases computation is simply impossible using current methods because we cannot hold enough data in memory at once. The Broad Institute led work to create reduced BAMs, “a new way of storing that raw sequencing read data in a format that allows us to actually actively pull the variants in a very large number of samples.” MacArthur’s lab is using a joint calling approach that combines data generated with different software. The pilot run included 25,000 samples, generated more than 350 Tb of raw data, and required more than 150,000 CPU hours of processing and joint variant calling. But it worked. MacArthur gained the largest ever catalogue of human protein-coding genetic variants.
In a session on the pros and cons of consumer testing, Ellen Matloff, Director of the Cancer Genetic Counseling Center at Yale Cancer Center, presented a GAO report from 2006 highlighting issues with direct to consumer tests. Matloff called some practices “criminal” (specifically the 23andMe recommendations included in the report for patients with positive BRCA findings), and questioned the practice of ever providing genetics results without counseling.
Gholson Lyon disagreed. After recounting a successful deep brain implant in a patient with severe mental illness, Lyon says it puts sequencing in perspective. “I put a device in a guy's brain. Now that's serious. Getting our genomes sequenced? This is what we're worried about?” The medical community has lost its way, he said. We don’t have to go with them.
The New Class
A host of new players and products were presented covering the gamut of sequencing options.
Jessica Richman, CEO and co-founder of uBiome (ubiome.com), presented a different consumer genetics engagement model, raising $350,000 with an indiGogo crowd-funding drive. The financing model is just the first difference, said Richman. The company, which sequences patient microbiome from stool samples, is “throwing out” the old assumptions that patients get most of their information from doctors and that the customer is an insurance company, and is instead embracing a paradigm where patients are bright, creative, and engaged.
On the heels of Foundation Medicine’s IPO, GENEWIZ (www.genewiz.com) announced its forthcoming PGxOne and OncoGxOne tests. Guanghui Hu, VP of translational genomics, described the tests as not “me too” solutions, but “me better” versions of the FoundationOne test. The tests can detect a full range of mutations: copy number variations, SNPs, insertions, deletions, gene fusions in introns, and low-frequency aberrations.
Ian Curry, president of DNA Genotek (www.dnagenotek.com) gave insight into DNA sampling and collections options—crucial questions as sequencing moves every closer to the consumer and medicine highlights home care. DNA Genotek samples are stable at room temperature and can be sent through standard mail. They can be banked for years at room temperature without even a freezer.
GnuBio (gnubio.com) presented its new sequencer—as yet unnamed—built on fluidics. Using emulsions and 10,000 uniplex reactions per second, the GnuBio system needs 1/1000 of sample compared to other sequencers, said John Boyce, President and CEO of GnuBio. Boyce says GnuBio aims to be “the K-cup of sequencing,” eliminating sample prep. The $50,000 GnuBio system uses $200 disposable cartridges, can handle 50 genes, 5% allele frequency, and weighs 80 lbs. Boyce reported 1 error per million drops across all experiments using raw data.
Anne Morriss, the founder and CEO of GenePeeks
(www.genepeeks), spoke about her company’s business and corporate culture. GenePeeks offers prospective mothers who use sperm banks the opportunity to screen donors for the possibility of dangerous recessive diseases for which both parents are carriers. But Morriss believes that as the consumer genetics industry becomes more crowded, novel services like GenePeeks can’t rely on innovation alone. “We decided we were unambiguously in a service business, and service had to be one of our advantages,” said Morriss. To that end, education in the genetics of recessive disorders, and offering genetic counseling at every stage of customers’ decision making, will be an integral part of GenePeeks’ strategy. Morriss hopes to launch GenePeeks’ commercial services in the fourth quarter of 2013, and is already thinking of expansion into the couples market, although she acknowledges the ethical considerations are more complex. You can read more about GenePeeks, and Morriss’ own story, at Bio-IT World
Focusing on the digital health market, Julio Oh and Anish Sebastian of 1EQ (www.1eq.me) presented their vision for consolidating genomic data with the health record with data from personal health devices like the FitBit and Jawbone Up. The FDA released guidelines this week saying they would not review a lot of health and wellness apps, and Martin Mendiola of Happtique (www.happtique.com) presented their vision for stepping into that space. The company was spun out of the Greater New York Hospital Association, and is offering certification for health and wellness apps for $3,000 each for content, patient data security, and more.
, Director of the Genographic Project at National Geographic and a luminary in the field of using genetics to illuminate human origins and migration patterns, delivered the closing keynote. In addition to reviewing the success of the Genographic Project, which since 2005 has performed over 600,000 genetic tests on people around the world and distributed $1.9 million in Legacy Funds to preserve traditional cultures, Wells also offered his predictions for the near future of consumer genetics. “The big inflection point has happened this year,” said Wells. “We’ve surpassed a million [customers purchasing genetic testing kits]… The cool thing is, it’s [only] going to take a year to hit the next million.” To continue driving growth, Wells encouraged the industry to make ancestry and genealogy its primary focus, pivot to international markets, and offer a “citizen science” experience to users. “Harnessing the community as part of the scientific process is something I hadn’t anticipated in 2005,” he said, recounting the story of a woman of Hungarian ancestry who insisted that Central Asian traces in her genome had to be the result of a faulty test. Her questions led the Genographic Project to finally confirm the genetic impact of the Magyar people on present-day Hungarians. This sort of result, Wells believes, shows the promise of collaborations between scientists and consumers as the industry continues to expand. You can read more about the Genographic Project
at Bio-IT World