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Neil Winegarden, M.S.

Head of Operations  |  University Health Network Microarray Centre - Toronto, Canada

Solving a Decade-Old Problem with NanoString Technologies

The University Health Network Microarray Centre in Toronto originally started in 1998 as a service lab devoted to making microarrays for the local research community. Since then, the Centre’s 28 staff members have provided a growing number of services to more than 700 labs in more than 27 countries.

Among the range of new technologies used by the UHN Microarray Centre is NanoString’s nCounter Analysis System, described by Head of Operations Neil Winegarden as “a universal tool that can be used to validate results from any of our array platforms” and with its expanding applications, emerging as “a key tool in helping uncover the biology involved in disease.” Those diseases include breast, prostate, ovarian, and head and neck cancers, as well as infertility.

The nCounter Analysis System has solved a fundamental problem in the delivery of service at the UHN Microarry Centre, explains Winegarden: “One thing we heard from customers from the beginning of our operations was ‘What do we do with all of the genes we have identified in our microarray study? We’ve identified 200 or 600 genes that are changing. What do we do with that?’ And for the longest time the answer was always, ‘all you can really do is pick 10 of them, go do some qPCR and see what you get.’ That was an unsatisfactory answer for a lot of reasons.”

Using a small number of genes to validate a larger gene set has a number of challenges, but was previously the only way to cost-effectively validate a microarray experiment. Typically one of two things would happen, says Winegarden – either all 10 genes would validate, and then people would think all 200 of their genes are valid (“Which statistically we know is not true”), or half of them validated and they would be left with a list of 100 that they thought were right, but didn’t know which 100.

When Winegarden first learned about the NanoString technology he thought it might solve that decade long problem they had. He ran a few test samples. “The data were so compelling – we said yes, we are going to invest in this technology.”

“The beauty of the NanoString platform is you no longer need to pick those 10, you can do all 200. You can validate all of them and eliminate the guess work, without really sacrificing anything that qPCR brought to the table.”

The system is now up and running in the Centre, which also served as an early access site for the miRNA CodeSets release last spring. “The response has been terrific,” says Winegarden. “Everyone who sees it says ‘That’s amazing, I want to try that.’ And once they do, they are hooked, he says. “It’s really been quite amazing. Everyone who’s used it has come back, not only to do more, but to do substantially more than they originally planned. They have all been sold on the quality of the data.”

While he was initially attracted to the nCounter system as a more effective tool for validating microarrays, he now also sees it as a valuable tool to use for ongoing testing as well. “If you’ve got your gene set there is no need to go back to doing an array – the NanoString technology is much higher throughput, much more quantitative, and is more cost effective,” he says. “I see it having a lot of potential use as an ongoing testing tool, whether that be in a clinical setting, basic research, or a drug discovery setting.”

At least one group of his customers has already begun using the technology for the first phase of high throughput testing of validated cancer gene signatures. And compared to other PCR-based ‘midplex’ analysis solutions, Winegarden says he believes the NanoString platform offers advantages because it handles degraded RNA better. And he trusts the gene expression data from this platform more because the RNA hasn’t been manipulated with enzymes.

Winegarden says the miRNA assays have been a welcome addition to the nCounter portfolio. “We had been struggling to come up with an array based platform that worked well for miRNA analysis,” he said. “In terms of speed and cost effectiveness, the NanoString platform is extremely hard to beat.”

So far about half of his customers that are using the nCounter CodeSets for gene expression analysis and also using the new miRNA CodeSets to integrate results for a better picture. “Beyond just a biomarker, in order to really understand the biology of the disease you need to be able to see both sides of the equation.”

He says he is also eager to try the newly launched assays for copy number variation, since, like the miRNA assays, the system can be used to determine if these changes are having a biological effect.

“The diversity of applications on the nCounter Analysis System is a big deal for me,” he notes. “Gene expression, miRNA, and CNV have already been captured, and the potential of the NanoString technology for other types of genomic analysis makes it a universal tool in terms of what type of biology we want to look at.”