The new system, known as VirCapSeq-VERT, barrels past this limitation. Lipkin, together with fellow Columbia professors Thomas Briese and Amit Kapoor, designed it to detect all known human viruses, quickly, efficiently, and sensitively. By searching for thousands, perhaps millions, of viruses at once, it should take a lot of the (educated) guesswork out of viral diagnosis.
In the 120 or so years since viruses were first discovered, our ability to identify them, and diagnose the diseases they cause, has improved enormously. But even the most cutting-edge of techniques have limitations. Sequencing technologies allow scientists to unambiguously decipher the genetic material of viruses in a sample, but they suffer from poor sensitivity—that is, they sometimes miss what they're trying to find. That's because viral genes are often swamped by those of their hosts, so sequencing them is like trying to find a needle in a haystack.
PCR, a method for amplifying DNA, solves that problem by making lots and lots of copies of the needle beforehand. It is exquisitely sensitive but it's also hard to do in bulk, and you need to have some idea of what you're looking for in the first place.
VirCapSeq-VERT combines the best features of these techniques, and throws in a few more for good measure. Think of it as a massive exercise in fishing for viruses. To make the hooks, the team identified and synthesized distinctive stretches of DNA from the genomes of every known group of virus that affects humans and other vertebrates. They ended up with two million of these hooks, each of which was baited to snag a different virus. If you dangle them in a blood sample, yank them out, and then sequence everything that's attached to them, you end up with the full genome of every virus present.
The team tested the system using tissue samples spiked with genes from many infamous viruses, including those responsible for Ebola, dengue, flu, and MERS. They also tried analyzing a nasal swab from a patient and a stool sample from a bat. VirCapSeq-VERT successfully identified all the viruses in these samples, even when they were present at miniscule amounts.
And since the technique offers up the full genomes of whatever virus it detects, it shouldn't throw up any false positives. “If you get a genome, you know what it is. It's unequivocal,” says Lipkin. “It also allows you to find mutations that would circumvent traditional diagnostics, or that might would affect resistance to drugs or vaccines.”
The team can also analyze many patients at once. To do that, they fuse a unique barcode sequence to the viral DNA from each individual sample, before mixing them together and running them through VirCapSeq-VERT. After the system does its thing, the team can check the barcodes to work out which sample each virus came from. “We can do up to 21 at a time, which makes it financially viable,” says Lipkin.