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Is Next-Gen Technology Right for Your Lab?

[April 2008]

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By Meredith Salisbury

The hype around next-gen sequencing is at fever pitch. And while in many ways that's actually deserved with tools that promise to be as revolutionary as these do, it's worth remembering that this technology isn't a good fit for every lab. Though genome centers are amassing fleets of next-gen instruments, some users say that smaller labs might be better off using a service or finding a core facility than investing in the technology themselves.

If you find yourself torn between the lure of buying a next-gen sequencer — along with the fear that not having one will make your grant proposals less competitive — and trepidation about such an investment, here are a few factors to help you decide whether your lab is really next-gen ready.

Data management. The flood of data from a next-gen sequencer may very well take you completely by surprise, despite how well you've noted the file size generated by each type of sequencer. "Really, the data management is something that is so new," says Agnes Viale, who runs the Genomics Core Laboratory at Memorial Sloan-Kettering Cancer Center and has purchased both a 454 instrument and an ABI SOLiD. Her experience with large micro-array data sets was nothing compared to the onslaught of data generated by the  sequencers, she says. The new instruments challenged even data systems Viale had never questioned; her network speed, for instance, was too slow to transfer a file to the typical data storage facility. Factors for any lab to consider, she says, include: "Are you going to need to upgrade your network? Do you have enough storage? Are you going to need to hire somebody to manage the data?"

Peter Schweitzer from Cornell told attendees at the Association of Biomolecular Resource Facilities that "most labs really don't have a concept of what it takes to analyze these data."

Cost. Sure, you know about the price tag of the instruments. But budgeting for that alone is like buying a car and forgetting that you'll need to pay for gas and insurance. Viale says that when she bought her SOLiD, she budgeted $900,000 — even though the sequencer itself cost closer to half a million dollars. The extra funding covered data storage upgrades, technical staff for the instrument, and other ancillary items. Also, some of the instruments are finicky about what kind of space, temperature, or other conditions they'll live in; any retrofitting of your lab to accommodate these needs must be included in your budget as well.

Personnel. Unlike your old 3730, the new sequencers generally can't be considered low-maintenance. Viale says the labeling steps required for the 454 were such that "it was clear that I had to put my most senior person" on that process. If you don't have a top-notch technician on staff, you might need to hire someone with the right experience. "The technology is really evolving very, very fast," says Jakub Sram at City of Hope's Clinical Molecular Diagnostic Laboratory, "so someone has to keep up with the technologies." That goes for watching technologies on the horizon as well as keeping up with ever-changing protocols for whichever instrument you have in your lab.

Quality control. For the most part, says Sram, "next-gen systems don't work right out of the box." Especially if you're in a core facility, expect to put in a significant amount of time — this could be weeks or months, judging by some users' experiences — to get everything working to your satisfaction with the error rate that you expect. "It takes a long time to set up quality control," Sram says.

Feedback from others. So what's a scientist to do? Several steps can help you make sure you're prepped to buy a next-gen sequencer. For starters, send a sample out to the vendor and check the sequence data you get against your own sequence of that sample. Viale says she learned a lot by visiting the vendors because "you get to talk to the people who actually do the work." She also recommends talking to other users before buying. "One really has to adjust what you hear and see to your size operation and to your institutional capabilities," she says.


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