Mystery microbes

Stanford scientists developing noninvasive ways to detect organ-transplant rejection discovered something that gave them a new appreciation for the wide diversity of the human microbiome.

Illustration by Brian Cairns

Traditionally, doctors detect rejection with a biopsy of the transplanted organ itself, a procedure that requires at least an afternoon spent recovering in the hospital.

Stephen Quake, PhD, professor of bioengineering and of applied physics, and his team theorized that it might be possible to detect rejection through a less-invasive test: scanning blood samples for organ donors’ DNA.

Over the course of several studies, the first of which was published in 2013, Quake and his colleagues collected samples from 156 heart, lung and bone marrow transplant recipients, as well as from 32 pregnant women. Those samples confirmed that blood analysis could detect levels of donor DNA, a sign of rejection, but they also provided data on bacteria, viruses and other microbes that make up a person’s microbiome.

“We found the gamut,” says Quake, senior author of a study published online Aug. 22 in the Proceedings of the National Academy of Sciences. “We found things that are related to things people have seen before, we found things that are divergent and we found things that are completely novel.”

Of all the nonhuman DNA fragments the team collected, 99 percent of them failed to match anything in existing genetic databases the researchers examined. And when the team started characterizing the mystery DNA, they zeroed in on a host of viruses that had never been identified.

“There’s all kinds of viruses that jump from other species into humans, a sort of spillover effect, and one of the dreams here is to discover new viruses that might ultimately become human pandemics,” Quake says.

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