AI analysis maps the world’s biggest killer virus to cultivated bacteria

Through cutting-edge methods and advanced artificial intelligence analysis, UNC Charlotte researchers leading an interdisciplinary team across four universities have solved the complete genome of “Phage G,” the largest bacterial virus (also known as phages or phages) ever grown in a physical laboratory setting.

Studied by multiple laboratories around the world for more than 50 years, these large phages (e.g., Megaphage) have now been fully mapped for the first time, thanks to this effort led by Charlotte. Given the proximity of computer science and life sciences at UNC Charlotte’s Center for Computational Intelligence for Prediction of Health and Environmental Risks, also known as CIPHER, the use of artificial intelligence is coming to the fore and revolutionizing science to solve life-threatening problems such as multidrug-resistant bacteria.

Published September 30 In the magazine, npj virusesthe study was led by master’s students in UNC Charlotte’s School of Computing, Informatics, Bioinformatics, and Genomics Andra Buchan and Stephanie Weidman along with Assistant Professor of Bioinformatics and Genomics Richard Allen White III, who is also a faculty member at the North Carolina Research Campus and the Charlotte Institute for Artificial Intelligence. Collaborators from three other institutions were instrumental in this effort: Julie A. Thomas of Rochester Institute of Technology’s Gosnell School of Life Sciences, Kebin Zhang of the University of North Carolina at Greensboro, and Philip Serwer of UT Health San Antonio.

Environmental DNA sequencing has shown that megaphages are extremely widespread—from deep in the guts of humans to natural ecosystems—but have historically only been detected by counting environmental DNA data. Typically, researchers have not been able to grow and culture these megakaryocytes under laboratory conditions.

In contrast, Phage G is the only megacell that scientists can grow in laboratories and the first of its kind that can actually be observed inside a laboratory. This allows researchers to perform direct experiments, provide a new model system for studying macrophages and build the tools needed to push research and applications even further.

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Phages infect and kill bacteria and reproduce exclusively within bacteria. They do not directly cause disease in humans but can modify bacteria in ways that cause disease or promote health. Phages have long been of interest to scientists, including Buchan, Weidman, and their fellow researchers at the White Research Laboratory of the University of North Carolina at Charlotte.

Phage G is huge in size compared to other phages, being three times larger than many phages. Its enormous size is proportional to the level of mystery surrounding it. Phage G has much in common with another large phage found computationally through analyzes of environmental DNA from moose guts.

Curiously, Phage G does not appear to use moose as a primary host. For decades, some scientists have shared an apocryphal story about an unknown graduate student in Rome tracking phages in their research laboratory. Currently, the true origin of phage G is unknown.

In terms of applications, phages can be used as an alternative or complement to antibiotics to combat increasingly resilient diseases. “Bacteriophages have a lot of applications in healthcare right now, especially in light of the ongoing antimicrobial resistance crisis,” Bhushan said. “Think of them as packages of DNA that you can deliver to the source. We think it’s a great way to transfer genetic information to attack the target.”

“Macrophages are found throughout our bodies and in the environment. However, their cultivation has proven elusive. Thus, G phage provides us with an invaluable model to study megakaryocytes in the laboratory,” White said.

“Basically we are trying to determine what environment drives viruses to evolve to this size, and what selection provides a niche that allows them to coexist with smaller, faster-growing viruses under enormous competition.”

Thanks to the advanced computational techniques White uses with his students, including artificial intelligence-based analysis methods to predict Phage G classification, life cycle, and protein structure, UNC Charlotte researchers like Buchan and Weidman can move their field forward with transformative applications for fighting disease and promoting health.

“Biological data is notorious for the amount of noise involved, so all these AI tools are really important for understanding everything,” Weidman said. “Working at UNC Charlotte, we have demonstrated first-hand the importance of these computational tools.”