New tech can detect even viruses yet to be discovered

Researchers say a next-gen sequencing approach allows them to subtract the entire human genetic sequence from the genetic material of a blood sample and identify viruses based on what remains.

The coronavirus is now recognized as the etiologic agent of the 2003 SARS outbreak, and appears to be behind the new SARS-like virus that has recently killed dozens in and near Saudi Arabia. Centers for Disease Control and Prevention

Sometimes a concept is simple but the tech behind it is not. This is the case with a new approach to identifying new viruses, which could ultimately lead to screening patients for viruses that haven't even been identified. (Think of the one currently rearing its deadly head in the Middle East.)

Researchers at Saint Louis University are using the next-gen sequencing approach transcriptome subtraction, and it really does employ basic arithmetic -- with very fancy tools. They take a human blood sample. Then they subtract the entire human genetic sequence from the genetic material in the sample. Then they study what remains, thus enabling them to identify previously unknown viral genetic data.

Adrian Di Bisceglie Saint Louis University

Sounds simple enough, but Adrian Di Bisceglie, chairman of the department of internal medicine, sums up what this actually entails:

"We isolate DNA and RNA, amplify the amount of genetic material present in the blood, do ultra-deep sequencing, and use an algorithm to search for matches for every known piece of genetic code, both human and for microbes," he says in a school news release. "Once we remove the known portions, we're ultimately left with new viruses."

Researcher Xiaofeng Fan, associate professor of internal medicine at SLU, says the key to their work lies in the second step -- discovering how to amplify the genetic material in the blood. Because RNA degrades so quickly, blood samples have until now been unviable because there was too little material left to study. By amplifying the genetic material, however, the size was no longer an impediment.

Viruses are tricky little beasts. Even when a viral infection is obvious, determining which virus caused it can be a challenge. One approach is to grow the virus in a lab using tissue or blood, but if there is no obvious starting point to test (i.e. knowing a patient was exposed to a specific virus), or if time is of the essence, this approach won't cut it.

Another is to search for viral genetic material, and while various techniques to do this already exist (i.e. mass spectrometry and DNA microarray), the transcriptome subtraction approach allows for the discovery of entirely new viruses by comparing the viral material being tested to the database of known viral material.

This allows researchers to not only identify any known viruses in the blood, but also to scour the remaining, unmatched material using specific protein signatures that mark every type of microorganism and then parsing out the viruses from the bacteria and phages. It is the newly discovered viruses that become the area of interest.

The technique, outlined in the journal Biochemical and Biophysical Research Communications, could be used sooner than later considering the new SARS-like virus out of Saudi Arabia that has already killed dozens and appears to be part of a family of viruses of unusual size (called coronaviruses) that often cause the common cold, among other illnesses.

"Just as the human microbiome project is chronicling the bacteria that live and co-exist in every person, we also are studying the human virome to know more about the viruses that live in all of us," says Di Bisceglie, who adds that, as with bacteria, some viruses may turn out to play positive roles in our lives. "We believe not all are harmful and some may even be beneficial."

Saint Louis University has applied for a patent of the new tech and is now pursuing commercialization.

 

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