By Julia Karow
This article has been updated from a version posted June 3 to include additional comments from Illumina CEO Jay Flatley.
Illumina said last week that it is cutting the price of its individual genome sequencing service by 60 percent or more and expects a greater number of both healthy consumers and patients with cancer or other genetic diseases to have their genomes sequenced as a result.
At the Consumer Genetics Conference in Boston last week, Illumina president and CEO Jay Flatley said that the firm has sequenced 14 human genomes since it launched the service a year ago.
"We think we are at the tipping point of human genome sequencing, where the number of genomes both in the research market and in the consumer space is about to explode," he said.
Citing the analysis of his own genome, which initially yielded a number of invalid and spurious results, he said that the greatest challenge will not be the generation of sequence data but its interpretation. "It's easier and easier to create the datasets — it's increasingly difficult to extract valuable information and figure out how to apply that to an individual," he said.
Interpreting growing numbers of genomes will also require a more automated analysis and display of the results. To that end, Illumina has been developing an iPad application, which Flatley demonstrated during his talk, that will allow users of its service to browse analyses of their own genome.
Illumina introduced its individual genome sequencing or IGS service, which involves a physician and follows a "rigorous and responsible" process developed by the company, a year ago at a price of $48,000 (IS 6/16/2009).). The company sequences customers' genomes at its San Diego-based CLIA-certified, CAP-accredited laboratory using its in-house sequencing platform.
For individuals, the new price will be $19,500, while groups of five or more customers using the same ordering physician will pay $14,500 per person. In addition, individuals with serious medical conditions for whom whole-genome sequencing could be of clinical value will pay $9,500 to have their genome sequenced.
At present, Illumina has a couple of Genome Analyzer instruments dedicated to the service. Flatley told In Sequence on the sidelines of the conference that the firm plans to add more instruments, including HiSeq 2000 machines, depending on how much demand for the service will increase as a result of the price cut.
During his presentation, he said Illumina would be able to sequence "hundreds" of genomes but finds it hard to anticipate the demand. "We don't know if the answer is 50, 500, or 5,000 [genomes] in the next 12 months."
Potential customers include both individuals "who have some clinical reason" to have their genome sequenced, as well as healthy people "who are just curious," he said. "As we create more and more value [from the analysis], and more goods are delivered back, you are going to see the curve go up quite rapidly."
However, Illumina is not planning to grow its consumer sequencing service to become a major part of its business, but rather to help others offer similar services on its platform. The goal is to "grow the industry faster than it would on its own," Flatley said. "We do have many service providers around the world, and to the extent they are interested in entering this business — and some are — we are going to help to enable them."
So far, he said, Illumina has sequenced 14 genomes from 13 individuals through the service, including those of Flatley; former Solexa CEO John West and three members of his family (IS 4/20/2010); Hermann Hauser, a Solexa investor; Skip Gates, a Harvard professor for African American Research and his father; actress Glenn Close; two centenarians; a cancer patient, who had his tumor and a healthy tissue sequenced; and, most recently, a severely ill child with a genetic disease where the underlying mutation was unknown.
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In order to track the number of consumer genomes sequenced worldwide, Illumina has also created a web-based database called the World Genome Registry which will go live in the next few weeks. The registry will contain basic technical information about each project, including the date a person's genome was sequenced, the technology platform used, and the sequence coverage. Illumina is still deciding whether the data is going to be self-reported or gathered in other ways, and plans to hand the database over to a "standards body" sometime after it has been established.
Physicians play an important role in the IGS service, Flatley said, especially in setting customers' expectations. Last year, Illumina founded the Personal Genomics Network, a group of physicians familiar with its service. The PGNet currently has members in the US and the UK, and Illumina plans to build it out and add physicians from other countries soon, he said.
For the secondary data analysis, Illumina originally partnered with 23andMe, DecodeMe, Knome, and Navigenics. Recently, the company added the National Center for Genome Resources, a Santa Fe-based research institute, and Pathway Genomics as partners, Flatley said.
But Illumina has also been working on its own software — an iPad application — to make genome sequence analyses accessible and useful for its customers. At "some point in time," it will deliver the application, which it plans to improve over the next four to six months, to its customers, Flatley said, although it has not yet decided whether to make it widely available on its own.
The application, which Flatley demonstrated during his talk, lets users build a family tree and fill in their own medical history and basic phenotypic information such as height and weight. Over the Internet, these data can be synchronized with their medical records held in Microsoft's HealthVault. The application also lists diseases that are associated with certain variations in the genome and provides pharmacogenomics information. Users can also get reports on "favorites" they want to track, such as "athletic tendency," and can explore variations in specific genes, such as the ApoE gene, which is associated with Alzheimer's disease. In the future, Illumina also wants to add a genome browser and gene pathway information, and enable customers to share the information selectively with physicians.
But the value of the interpretation hinges on the quality of the databases used for the annotation, which Flatley said are "woefully lacking."
As an example, he cited the analysis of his own genome, which Illumina analyzed using primarily the Human Gene Mutation Database, HGMD, which was established by researchers at the University of Cardiff in the UK, and the Pharmacogenomics Knowledge Base, PharmGKB, which is managed by Stanford University.
The initial analysis found that Flatley possesses 16 homozygous and 48 heterozygous disease-causing mutations, and that most of the homozygous mutations were associated with conditions leading to death in early infancy. However, the researchers were able to eliminate all 16 of these associations based on manual literature and database reviews, as well as all but 11 of the heterozygous disease associations. "The conclusion was that [the remaining] variants and the diseases they are associated with are clearly compatible with life," Flatley said.
Since the annotation databases were originally created by researchers to submit their study results, they are "not as highly managed as we'd like," Flatley said. There is "a need to create more robust databases and collections of those variants that can be applied safely" in the interpretation.
Another challenge will be to provide interpretations that are straightforward enough so physicians — most of whom are not well versed in genetics — can apply them routinely. While physician education is an important component, Flatley said, "as an industry we probably have an equal challenge to abstract the data in ways to make it less and less important for physicians to understand the genetics" but to grasp the health implications of the results.
To address this, Illumina has been working to create so-called "risk variant objects," objects that connect clinically validated variants with their medical and pharmacological consequences, that the company wants to provide to physicians.