By Kevin Davies
June 20, 2012 | The renowned Hospital for Sick Children in Toronto, Canada (SickKids), will feature the Ion Proton sequencer from Life Technologies when it launches a whole-genome sequencing program at the new Centre for Genetic Medicine.
The new center will include four Ion Proton instruments initially – the first in Canada to feature the promising platform from Life Technologies. The long-term goal is to sequence 10,000 patient genomes per year, which the Centre’s co-director, Stephen Scherer, believes is attainable within a few years.
Scherer, who briefed Bio-IT World on the announcement, says the Centre for Genetic Medicine brings together many ongoing activities into a single hospital unit, including the Centre for Applied Genomics; a large (if not the largest) molecular diagnostics lab in Canada; a clinical genetics group; and a genome sciences department. The center’s other co-director is Ronald Cohn, who arrives from Johns Hopkins Medical School.
“The Hospital is putting in resources to create an environment -- physical and human -- to prepare for day when every sample is sequenced,” says Scherer. Scherer says SickKids management is making preparations for the day in the not-too-distant-future when whole-genome sequencing becomes essentially routine.
The Ion Proton sequencers will be used initially for exome sequencing, but once the second-generation chip is released (sometime in early 2013), “that’ll move us into the realm of whole-genome sequencing,” says Scherer.
If the machine delivers quickly, he says, the center will gear up to perform sequencing on 10,000 samples annually, especially if the sequencing cost drops to $1,000/genome. The number of microarray and targeted gene sequencing analyses performed at SickKids are close to that number already, says Scherer. “Ideally, we’ll just replace [them].”
The selection of the Ion Torrent platform is based in part on familiarity with the hardware, says Scherer. The genome center runs all the major next-gen sequencing platforms, but to jump into whole-genome sequencing, Scherer believed it was worth waiting for a major leap in the technology.
“By my interpretation, we needed to wait for a ‘next-next-generation’ platform. With the Proton, the promise is the turnaround time. In clinical diagnostics, a half-day experiment was a critical thing.” A second factor is cost – and while Scherer says there’s probably not much in it, he feels the Ion Proton may be fractionally cheaper to run than say the Illumina HiSeq.
“If another vendor came forth, we’d look, but for now we think this makes sense,” he says.
As for the question of exome versus whole-genome sequencing (WGS), Scherer says the topic has been examined by a working committee. “Looking at the yield and data, we decided that we’re waiting to make the jump to go into the hospital setting… It was unanimous: why waste our time on an intermediate step?”
Scherer’s group has been gaining experience in WGS, outsourcing some projects to Complete Genomics and also entering a large collaboration with BGI in autism.
The situation resembles what has happened in recent years in the microarray field, says Scherer. “Based on our research findings in autism and other findings, the Provincial [Ottawa] Government is now funding clinical microarrays. We’re probably running 10,000 clinical microarray samples. We anticipate, once up and running in a few years, that instead of doing clinical microarrays, we’ll be doing sequencing to get the highest resolution analysis.”
According to Scherer, the plan is that all whole-genome sequencing studies will be done in a CLIA approved environment, starting initially with research studies but moving towards every clinical diagnostic sample being part of a grander hospital-based 'research study'. In the long term, the new Centre for Genetic Medicine will move a range of DNA-based tests to WGS, use the same technology for research studies, and develop the appropriate consents and environment such that the two streams of subjects are treated equally.
Clouds Up North
Scherer is realistic that the introduction of the Ion Proton platform will pose a big challenge on the information systems at SickKids.
“In Canada, we’re still developing these [IT] resources [and fall back on] using US infrastructures. We hope to jump start a larger project so the entire hospital system can generate and process the [clinical genomics] data and ultimately, to develop the clinical structure to help the families make sense of the information,” he says.
When it comes to putting clinical data in the cloud, Scherer says it can be done if the data are completely anonymized. “But the consensus in Toronto, once we move into healthcare, is that it will be beneficial to have the cloud infrastructure here. As the technology goes forward, the analyses and computational requirements will come in house, but that will take time,” he says.
The Toronto team has plenty of experience in exome sequencing, including its role in the Canadian FORGE (Finding of Rare Disease Genes in Canada) consortium. “We’ve done hundreds of families… with 50 disease genes identified,” says Scherer. It has also gained experience in seeking informed consent, confronting issues of serendipitous findings, and so on. Moreover, he adds, “when we find something medically relevant, we have a better system [in Canada] to follow up, collect families, and so on.”
“Genomic medicine is unique to the individual,” Scherer says in closing. “But how you roll it out in a healthcare setting depends on the jurisdiction and the payer. In Canada, healthcare goes through the Provincial Government, and the hospital controls its budget. We’re learning from other groups, but to set something up, you have to set it up at your own institution.” Naturally, as the largest pediatric hospital in the country, SickKids aims to be the first to roll it out, says Scherer.
About 70 percent of the children admitted to the Hospital have some sort of genetic condition, Scherer estimates. “All those individuals will be sequenced at some point,” although he notes that the newborn birthing center is part of a different facility. Still, it is hard not to believe that the era of “sequence once/read often” is edging ever closer.
Meanwhile, Life Technologies is also announcing a collaboration with Boston Children’s Hospital, the world’s largest pediatric research operation and home to The Gene Partnership, to develop a comprehensive genetic sequencing lab workflow featuring the Ion Proton. The organizations plan to develop “an optimized laboratory infrastructure and lab protocols for an advanced sequencing facility to be built at Boston Children’s in compliance with CLIA and CAP certification standards,” according to a press release.