In November 2009, the West family embarked on an unusual family project. Parents John and Judy and teenagers Anne and Paul each had their genomes sequenced, and enlisted a team of scientists at Stanford University to interpret the meaning of the combined 24 billion letters of DNA in those genomes.
The findings, published today in the journal PLoS Genetics, are the first attempt to analyze the genome of a healthy family, a feat that gives family members clues to their future risk of disease, points to lifestyle changes that may help mitigate those risks, and highlights the drugs that are most likely to help or harm them. One of the major benefits of sequencing a family is that it generates much more accurate data, by allowing scientists to filter out sequencing errors. More broadly, the project hints at the future of personal genomics, capturing both the potential for preventive medicine and the challenges in interpreting the meaning of the genome for people who are largely healthy.
A major part of the project was developing streamlined tools for interpreting the vast complexity of the human genome. Such tools are becoming increasingly important as the cost of sequencing plummets—from about a million dollars per genome in 2007 to between $4,000 and $10,000 now—and as the number of sequenced genomes available for analysis grows. (John West, formerly head of Solexa, a sequencing startup bought by Illumina in 2007, paid Illumina $40,000 per genome in 2009.)
“Data is coming out thick and fast, and as a community of scientists and clinicians, we need to think about what we’re going to do with that,” says Euan Ashley, a cardiologist and head of the Stanford team. After helping colleague Stephen Quake interpret his genome last year—a project that involved synthesizing decades’ worth of scattered research on the human genome and figuring out how to apply it to a living, breathing person—Ashley’s team began getting calls from both individuals and researchers, and asking for aid in interpreting genomes.
Indeed, genome sequencing is at something of a tipping point. The cost of sequencing is now on par with diagnostic tests that analyze just a few genes, meaning that for those suspected of having inherited disorders, it now makes economic sense to sequence the entire genome rather than just suspect genes. “Even if these highly predictive and actionable [variations] are considered rare” collectively, “everyone is at risk and should be just as willing to spend on this as on fire insurance and other unlikely contingencies,” says George Church, a geneticist at Harvard who participated in both the West and Quake projects. Church’s group has done similar analysis of 64 genomes as part of the personal genome project, a nonprofit effort to sequence and interpret thousands of genomes.
Ashley, West, and two other collaborators have since founded a startup called Personalis to commercialize the tools they have developed. The company’s initial focus will be on analyzing genome sequences for researchers, but it ultimately aims to move into the clinical realm. “What’s going to happen when there are thousands of families like us?” says West. “We agreed it would make sense to set it up as a company.”
Hear more from Illumina at EmTech 2014.