SDSU computer scientist Rob Edwards
When SDSU computer scientist Rob Edwards discovered crAssphage in 2014, it was just the tip of a viral iceberg.
By Michael Price

When San Diego State University computer scientist Rob Edwards and colleagues uncovered a wholly new virus nicknamed crAssphage in the guts of about three-quarters of the world’s population in 2014, it was a startling discovery. Biologists marveled that such an abundant microbe was hiding right under our noses.

“The discovery of crAssphage … is arguably one of the most striking feats of metagenomics to date,” wrote biologist Eugene Koonin from the National Center for Biotechnology Information (NCBI) in Bethesda, Maryland, in a recent perspective paper published in the journal Nature Microbiology. “[Edwards’ finding] Was a true sensation and a shock at the same time.”

The virus—known as a bacteriophage, which infects and reproduces inside bacteria—was a secret for so long because traditional methods for viral discovery rely upon the ability to first cultivate them in a lab. If the bacteria they inhabit don’t grow easily in a petri dish, scientists never learn about the bacteria or their viruses.

Edwards’ innovation was ditching the traditional approach for a computational one. He and colleagues used computer software called cross assembly (hence the virus’s name) to sort through all the DNA and RNA present in a sample, separate out the known microbes, and locate the genetic signatures of a virus.

When Edwards and colleagues used the software a few years ago to scan gut microbes from human feces from around the world, they found the new bacteriophage, crAssphage in abundance, but they didn’t know whether the virus was a one-off discovery or if it was just the tip of the viral iceberg.

“One of the big unknowns was, is this phage unique?” said Edwards. “We found it in the human intestine, but we didn’t know if we would find it elsewhere.”

So Edwards and SDSU biologist Anca Segall teamed up with NCBI scientists led by Koonin to look for similar viruses elsewhere in nature, mostly in marine environments. They first pinned down key proteins in crAssphage—the virus’s genetic fingerprints—then looked for those patterns in dozens of microbial samples from around the world.

After analyzing the data, they were surprised to find that crAssphage’s viral cousins are equally abundant in nature, the researchers reported in Nature Microbiology. Though it remains unclear what role, if any, these viruses play in human health, identifying this widespread family of viruses could shed light on the evolution of viruses within our microbiomes.

Some of that work will likely play out in SDSU’s new Engineering and Interdisciplinary Sciences Complex, slated to open in January. The complex will house the Viral Information Institute, one of the world’s foremost research centers for viral ecology.

“[crAssphage] Is really a diverse virus that is all over the globe,” Edwards said. “When we identified it, we didn’t realize we had found something that would wind up being so widespread. It was sort of like we found the first tree without knowing about forests.”