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Genome X Prize Guidelines Hint at High Standards; Rules to be Finalized by April

NEW YORK (GenomeWeb News) — Two weeks after announcing the Archon X Prize for Genomics, the X Prize Foundation addressed the nitty-gritty of how to win.
 
The guidelines are out but not yet set in stone, according to Larry Kedes, a senior advisor and SAB co-chair for the genomics X Prize. For now, Prize organizers, who are in the process of lining up judges, want to know how they can improve the rules.
 
Kedes, director of the Institute for Genetic Medicine at the University of Southern California, gave a presentation last week at the Genomes, Medicine, and the Environment conference in Hilton Head, SC, during which he invited researchers to “tell us what’s wrong with [the guidelines and] where the flaws are” in order to “make sure nobody wins on a fluke.”
 
The foundation plans to finalize the rules within six months, and the competition, which can only take place twice a year, can start as early as next summer if teams are ready.
 
The prize is clear-cut: a $10 million cash award for the first team to develop a device that can sequence 100 diploid human genomes in 10 days for $1 million. At present, the bar for data quality is set very high: Sequence data submitted must cover 98 percent of each genome with no more than one error per every 10,000 base pairs.

“The bioinformatics of assembling 100 different genomes is certainly a gargantuan task by today’s standards. We are setting the bar far beyond today’s capabilities.”

 
In addition, the sequences must contain all insertions and deletions, rearrangements, copy number polymorphisms, complete genotyping, and correctly ordered and orientated sequences. Sequence segments must have a minimum length that is still being worked out.
 
Teams must also produce and assemble the data within 10 days, for $10,000 or less per genome, including all direct operating costs like reagents, labor, and power.
 
Those standards seem tough, but some researchers are pleased with the challenge.
 
“It is particularly gratifying to see that an endpoint of real sequence data of whole genomes has been chosen,” Richard Gibbs, director of the Human Genome Sequencing Center at Baylor College of Medicine, told GenomeWeb News in an e-mail message last week. “History is littered with DNA sequencing technologies that seem OK on paper or in prototype and gave encouraging results in pilots — but completely failed for practical reasons when applied to real problems.”
 
What might turn out to be the most daunting task is assembling the genome data within the 10-day timeframe. “That might be a harder problem by itself than generating 100 genomes of raw data for $10K each in 10 days,” Chad Nusbaum, co-director of the genome sequencing and analysis program at the Broad Institute, told GenomeWeb News by e-mail last week.
 
After creating the data, researchers would need to assemble them within a couple of days or so to the specified standards. “This I can’t imagine,” Nusbaum wrote.
 
“The bioinformatics of assembling 100 different genomes is certainly a gargantuan task by today’s standards,” Kedes said in an e-mail message. “We are setting the bar far beyond today’s capabilities.”
 
Another question nagging researchers is how the X Prize Foundation plans to determine which team got the right answers, or to verify the accuracy of their data. “This is an important component,” Gibbs pointed out.
 
According to Kedes, the X Prize judges “will use a number of methods to develop sufficient prior knowledge of each of the test genomes.” He did not reveal what these methods will be, but the guidelines said they will be “including direct sequencing from each of the 100 test genomes.”
 
But not even the currently available human genome might fully live up to the X Prize’s requirements, cautioned Kevin McKernan, senior director of scientific operations at Applied Biosystems’ high-throughput discovery unit.
 
Deanna Church, a staff scientist at the National Center for Biotechnology Information, agreed, telling GenomeWeb News by e-mail that while the current reference genome meets the standards for coverage and accuracy, it “does not represent all of the large scale variations” like copy number polymorphisms and indels. At present, “it is difficult to quantitate how much [of these] is missing because we don’t know how much is there,” she added.
 
In addition, the new sequencing technologies might generate data in areas where the current genome still has small gaps, so there would be no reference to refer to, Elaine Mardis, co-director of the Genome Sequencing Center at Washington University School of Medicine, pointed out in an e-mail message.
 
According to Kedes, another challenge will be to determine the cost accurately in order to make sure it stays within the $10,000-per-genome limit. “Accounting for the cost of sequencing will not be a trivial task for the judges and we need to clearly define how we will evaluate and measure costs,” he said by e-mail.
 
A panel of independent judges, to be chosen “closer to the time of an actual competition,” according to Kedes, will monitor each team round the clock during the 10-day period of the contest.
 
Who’s In?
 
Despite these challenges and unknowns, more teams are getting interested in entering the competition: In addition to VisiGen, 454 Life Sciences, and an academic-private consortium currently enrolled, three new teams have approached the foundation and are currently being evaluated, Kedes told GenomeWeb News.
 
Who is eligible? The competition is “open to any private team from any nation,” the guidelines read, thus excluding government-funded genome centers, for example. However, publicly funded researchers can join as part of a private team or company.
 
“Teams will be encouraged to find sponsors,” Kedes said, adding that “academic groups who build and operate a device with private funds are eagerly encouraged to enter the competition.”
 
Teams can compete twice a year — on Jan. 15 or July 15. The first possible competition will be July 15, 2007, and the competition will remain open until Oct. 3, 2013.
 
The genomes used for the X Prize will be from anonymous cell lines, according to Kedes. Each team has one shot for free, but if it fails to meet the standards, it has to pay for the cells and for the cost of the judges their second — and final — time round. If a team withdraws before receiving the cells it does not count as an attempt.
 
More than one team can try to meet the task each time, and up to three teams can share the $10 million prize — $7.5 million will go to the winner and $2 million and $1 million each to the runners-up — if more than one meets the criteria. The fastest team to reach the goal wins.
 
The winner will also have to sequence additional genomes “from up to 100 notable personages” within 24 months after the contest, a task paid for by the X Prize Foundation. These genomes currently include those of Stephen Hawking, Larry King, and Paul Allen, and will also contain “individuals afflicted with some heritable disease and others,” according to Kedes. “The exact mechanism for choosing these individuals is not yet finalized,” he said by e-mail.
 
At the moment, the foundation is hiring a “team liaison/contest logistics genomicist” as well as a volunteer to manage a blog where researchers can comment on the prize “and all its technical and social policy issues,” Kedes wrote.
 
But it may be some time before a team is ready to actually perform the task. “We think the first realistic attempt to meet the guideline criteria will be unlikely before two to three years,” Kedes told GenomeWeb News.

Julia Karow covers the next-generation genome-sequencing market for GenomeWeb News. E-mail her at [email protected]

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